Download Untitled

Welcome
Dear Students,
Welcome to the second year medicine. As you have already started in
the Faculty curriculum (System- Based Curriculum), this year you are in
Phase II of the program.
Phase I
: Premedical Year (First Year)
Phase II
: Second and Third Years
Phase III
: Fourth, Fifth and Sixth Years
Congratulations, you passed phase I. But what about phase II? Phase II
includes many core modules and also System-Based Modules. The aim of
this phase is to lay down a solid foundation for the subsequent full-time
clinical study in stage III of the MBBS program. It will also integrate the
basic sciences knowledge with the clinical sciences. This include knowledge,
skill and attitudes, particularly attitudes towards the learning process. The
curriculum philosophy in stage II is enforcing the development of a mixture
of teaching approaches including System-Based Learning, Problem-Based
Learning and also stressing on the idea of "Student Self-Directed Learning".
The department has the honor to introduce this study guide to you
hoping that it may be helpful in making you oriented with the aims,
objectives, contents of our courses, and through it, you will find the answers
of the frequently asked questions.
All the Best
Department Chairman
V
TABLE OF CONTENTS
TOPIC
INTRODUCTION
COURSE DESCRIPTION AND ORGANIZATION
MAJOR COURSE OBJECTIVES
STUDY STRATEGIES AND CLASS PARTICIPATION EXPECTATIONS
INSTRUCTIONAL METHODS
ASSESSMENT & EVALUATION
TIME ALLOCATION
CLINICAL BIOCHEMISTRY DEPARTMENT STAFF LISTING
DEPARTMENT WEB SITE
ICONS
TOPIC OUTLINES
NO.
LECTURES (NAMES)
01
02
03
04
05
06
07
08
VII
Page
09
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
VIII
NO.
PRACTICAL (Names)
01
02
03
04
05
06
07
08
09
10
11
12
13
14
TUTORIALS
01
Anatomy of the Heart and Big Vessels
02
03
04
05
07
08
09
10
IX
Introduction
Welcome to the Department of Clinical Biochemistry. The aim of this
course guide is to provide you with clear description of the course objectives,
contents of each topic together with its lectures, tutorials and practicals, which
are presented in a sequential manner. Also it states clearly what is expected from
you to achieve together with the evaluation procedures. There is no reason to
suppose that Biochemistry is intrinsically uninteresting, difficult to understand or
an obstacle to be overcome during your progress to a professional qualifications.
In the contrary you can enjoy its study if you remember the simple biological
principals that the body is formed from organs and tissues and these are formed
from aggregates of cells. The cell is build up from sub-cellular structures which
by itself is an aggregate of molecules. Every human actively, like walking,
breathing and even thinking are the result of the interactions of these molecules.
Defective molecular processes result in disease state. Moreover Biochemistry has
become a background subject for a great family of medical sciences.
Understanding Biochemistry will build for you a good foundation for
understanding disease states, their prevention, diagnosis and treatment. We
advice you to read the objectives of each topic before the start of its lectures and
focus your attention on the important points. Take another look after the end of
the lecture to make sure that these points have been understood.
Dr. Zainy Mohammed Abdullah Banjar
Chairman, Department of Clinical Biochemistry
1
Faculty of Medicine
Biochemical Basis of Medicine I
COURSE DESCRIPTION AND ORGANIZATION
The aim of Clinical Biochemistry II course for second year student is to
introduce you to the basic concepts of structure and metabolism in relation to
the mechanisms by which primary foodstuffs, proteins, carbohydrates and
lipids, are manipulated by the body in order to provide energy and to allow for
biosynthesis of cellular material. Also you will have a good view of storage,
transmission and expression of genetic information. Clinically relevant
examples will be discussed.
Biochemical basis of medicine I course includes and covers the following
topics: allosteric proteins, enzymes, membrane and transport, bioenergetics
and oxidative metabolism, anaerobic metabolism, tricarboxylic acid cycle,
carbohydrate storage and synthesis in liver and muscle, oxidative metabolism
of lipid in liver and muscle, biosynthesis and storage of fatty acids, lipid and
lipoproteins, and cholesterol metabolism.
The course consists of lectures, practical classes and tutorials.
Core Course
Code/No
Course Units
Credit Hours
Lectures
Practical
Tutorial
30
15
15
Biochemical Basis
Of Medicine I
2
3
Faculty of Medicine
Biochemical Basis of Medicine I
MAJOR COURSE OBJECTIVES
On completion of the course in Clinical Biochemistry I student will:
1. Evaluate the biochemical logic of the human cell.
2. Explain the maintenance of cellular life in the term of energy
production and biosynthetic ability.
3. Apply biochemical knowledge to solve problems of human health and
disease.
4. Practice basic skills in applying laboratory techniques encountered in
hospital's clinical biochemistry laboratories.
5. Appreciate the functional role of membrane proteins as pumps, gates
and channels
3
Faculty of Medicine
Biochemical Basis of Medicine I
STUDY STRATEGIES AND CLASS PARTICIPATION
EXPECTATIONS
The course offered to 2nd year medical students in clinical biochemistry consists of
scheduled lectures, tutorials and practicals which ensure smooth flow of the scientific material,
in a controlled manner, through several pathways to achieve our objectives. There is some
suggestion for optimal utilization of these classes by the students.
A. Lectures: The aim of the lecture is not to give information but to frame up the subject,
pointing out its relation to other parts of the course, its relevance to clinical situations and
to explain difficult points. To prepare your self for the lecture:
1.
Give a thorough look to the course objectives and the topic outline delivered by the
department and try to read the topic from the recommended textbook.
2.
Note taking in lectures keeps the student in track during studying the subject.
3.
If is recommended to study the topic of the lecture, if possible, in the same day, to
prevent fading of knowledge. You can utilize different ways of self-testing in order
to assess your grasping of the subject.
B. Practicals: For optimal utilization of the practical class time it is advisable to:
1.
Read your practical worksheet so as to have view of what is expected from you to
perform, observe and draw conclusions on your practical work.
2.
A record of the practicals should be used according to instructions.
3.
The practical time can also be used for discussing difficult theoretical or practical
points with the instructor.
C.
Tutorials: For optimal benefit of the tutorial, the tutorial will be reserved for open
discussion about the subjects listed in the tutorial schedule. The students will be
assigned these topics and will be asked to present them and be ready to change the most
recent knowledge about these topics and how to defend their thoughts on scientific
bases
4
Faculty of Medicine
Biochemical Basis of Medicine I
Instructional Methods
The main instructional material includes lectures, practicals to steamline the applied and
clinical aspects of the lectures and tutorials session to stimulate the students to participate
in the teaching/learning activities.
Instructional Materials And Resources
1. Required Texts And Resources
a. Lippincott Illustrated Reviews, 3rd edition, Champe & Harvey
b. Baynes, Medical Biochemistry, Mosby, London.
2. Supplementary Texts And Resources
a.
Thomas M. Devlin, Textbook of Biochemistry with Clinical Correlations, Jon
Willey & sons, New York.
b.
Lubert Stryer, Biochemistry, W.H. Freeman and Company, San Francisco.
c.
Pamela C. Champe, Biochemistry, Lippincott Raven.
5
Faculty of Medicine
Biochemical Basis of Medicine I
ASSESSMENT
1. Formative:
This form of assessment is designed to give you feedback to help you to identify areas for
improvement. It includes a mixture of MCQs, short answer-questions (SAQs), extended
matching questions (EMQs), problems-solving exercises and independent learning
activities in all subjects. These will be given during tutorial sessions and practicals. The
Answers are presented and discussed immediately with you after the assessment. The
results will be made available to you.
2. Summative
This type of assessment is used for judgment or decisions to be made about your performance.
It serves as:
a. Verification of achievement for the student satisfying requirement
b. Motivation of the student to maintain or improve performance
c. Certification of performance
d. Grades
In this Course your performance will be assessed according to the following:
1. Continuous Assessment
20 Marks
2. Assignment
20 Marks
3. OSPE
20 Marks
4. Final End of Semester Exam (Two Hours)
40 Marks
Total = 100 Marks
6
Faculty of Medicine
Biochemical Basis of Medicine I
All grades will be assigned as follows:
85 - 100
A
Excellent
75 - 84
B
Very good
65 - 74
C
Good
60 - 64
D
Pass
Less than 60
F
Fail
Exams: Exams will include short answer and multiple choice questions (MCQs). They will
cover material presented in lecture, readings, and discussion. All exams must be taken on the
date scheduled. In case of an emergency, the coordinator must be notified. No make-up exams
will be provided if you fail to notify and discuss your situation with the coordinator.
Assignment paper: The purpose of the work is to provide you with the opportunity to explore
an area of basic medical sciences or medical education in depth. The paper is to be a 10-15
page literature review of the topic will constitute 20% of your final grade. Policy: Topics must
be approved in writing by the coordinator. Directions for topic submission will be discussed
during the first week of class. Topics that have not been approved will not be accepted.
All papers must reference a minimum of eight references from refereed journals. All papers
must be typed, double-spaced, have 1 inch margins.
Note: We will be making the journey from "womb to tomb" in 15 weeks. Therefore, this
course requires an intensive coursework load. Class attendance and participation are extremely
important to your learning and as such are considered in the evaluation of your course grade.
This course is recommended for students that can make the required time and energy
commitment. If there is anything that the coordinator can do to assist you during the course,
please feel free to contact him.
7
Faculty of Medicine
Biochemical Basis of Medicine I
Time Allocations
BIOCHEMICAL BASIS OF MEDICINE
Topic
Lecture
Practical
Tutorial
BIOCHEMICAL BASIS OF MEDICINE I:
1. Allosteric proteins
3
1
1
2. Collagen
1
3. Catalytic proteins - Enzymes
7
3
4
3. Membrane and transport
2
4- Cellular transduction
1
5. Introduction to Metabolism, Bioenergetics,
2
1
1
6. Glycolysis
2
1
1
7. The tricarboxylic acid cycle
1
1
1
8. Gluconeogenesis
1
1
1
9. Glycogen metabolism
2
1
1
10. Pentose phosphate pathway
1
1
11. Metabolism of Monosaccharides and Disaccharides
1
1
12. Fatty acid oxidation
1
1
13. Fatty acid synthesis
1
1
1
14. Lipogenesis
2
1
1
15. Ketone bodies metabolism
1
1
1
16. Lipolysis
1
and the Role of ATP
Total
8
30
1
1
15
15
Faculty of Medicine
Biochemical Basis of Medicine I
CLINICAL BIOCHEMISTRY DEPARTMENT STAFF LISTING
The following is a list of the faculty members and staff of the Department of Clinical
Biochemistry. Students are welcome to contact any of the members of the department to
answer any of their inquiries.
Male Section: Men Medical Complex
Name/Status
Room
No
Phone No
Dr. Zainy M. A. Banjar
2/945 51-048, 22-116
B.Pharm., M.Sc., Ph.D.
2/948 22-101, 22-176
E-Mail Address
[email protected]
Office Hours
Daily
11.00-12.00
Associate Professor
Chairman
Prof. Adil Abdel Rafee
2/946 22-112, 22-194
M.B., B.ch., D.M.Sc.,Ph.D.
2/924 22-102, 22-173
[email protected]
Daily
12.00-1.00
Professor
Prof. Mohammed Ali Ajabnoor
2/942 22-100, 22-174
[email protected]
B.Pharm.,M.S., Ph.D.
Sat, Mon, Wed
1.00-2.00
Professor
Prof. Mohammed Saleh Ardawi
2/925 22-103, 22-177
[email protected]
B.Med. Sc., M.A., Ph.D.
Professor
Prof. Zohair M. H. Marzouki
B.Pharm., M.Sc., Ph.D.
G/640
51-701
zmarzouki@ Kau .edu .sa
12.00-1.00
2/853 22-099, 22-170
Professor
Prof. Abdulwahab A. Noorwali
Daily
Dean Off., Faculty of
Pharmacy
2/911 22-097, 22-172
[email protected]
2/852 22-098, 22-169
[email protected]
B. Phar., Ph.D.
Professor
Prof. Mohammed Zelai A. Abdu
B.Sc., M.Sc., Ph.D.
Associate Professor
Sat, Sun, Mon
1.00-2.00
9
Faculty of Medicine
Biochemical Basis of Medicine I
drmamdouhyoussef
Prof. Mamdouh Youssef Souaida
2/940
Sat, Sun, Mon
22-128
@yahoo.com
M.B.ch., M.Sc.,Ph.D.
Associate Professor
Dr Osama Abdul Aziz
M.B., B.ch., M.D.
1.00-2.00
2/910
22-096
2/941
22-118
[email protected]
Daily
8.00-10.00
mohammedhassanien700
Daily
@hotmail.com
WWW.kaau.edu.
8.00-10.00
Associate Professor
Dr Mohammed A Hassanien
M.B., B.ch., M.D.
sa/mhassanien
Assistant Professor
Dr. Mohammed Shoaib Jarullah
B.Sc., M.Sc., Ph.D.
2/912
22-130
Lab
22-120, 22-121
2/914
22-129
Lab
22-120, 22-121
2/922
22-117
Lab
22-120, 22-121
[email protected]
Technician
Mr. Khalil Fadul Al-Moula
B.Sc. Technician.
Mr. Ahmad Al-Shamrani
B.Sc.
Technician
10
[email protected]
Faculty of Medicine
Biochemical Basis of Medicine I
Female Section: Women Medical Complex
Name/Status
Prof Suhad Matoug Bahijri
B.Sc.,M.Sc., Ph.D.
Professor
Prof Enayat Mohd. Hashem
M.B., B.ch., h.D.
Professor
Dr Amina Mohd. Al-Ghareeb
M.B., B.ch., h.D.
Associate Professor
Dr Huda Gad
M.B., B.ch., h.D.
Assistant Professor
Dr. Eman Mokbel Alissa(BSc
MSc PhD) Assistant Professor
Dr. Fayza F Al Fayez (BSc
MSc PhD ) Assistant
Professor
Ms. Areej Al-Turki
B.Sc.
Technician.
Zain Mohd.AL-Shareef
B.Sc.
Technician.
Hana Abdullah Basaffar
B.Sc.
Technician.
Rehab Aboobakar Al-Aydoos
B.Sc.
Technician.
Nada Saleh Al-Saykhan
B.Sc.
Technician.
Reem Foad Ghazali
B.Sc.
Technician.
Room
No
2/510
Phone No
E-Mail Address
23-429
[email protected]
2/513
23-441
[email protected]
2/551
23-448
[email protected]
2/550
23-447
[email protected]
Office Hours
[email protected]
23-432
Webpage:
www.kau.edu.sa/ealissa
23-431
[email protected]
2/514
23-442
[email protected]
2/613
23-433
2/620
23-436
2/618
23-437
[email protected]
2/618
23-437
[email protected]
2/622
23-601
[email protected]
Department Web Site
www.kau.edu.sa/faculties/medicine/dcbcweb
11
Faculty of Medicine
Biochemical Basis of Medicine I
Icons
The following icons have been used to help you identify the various experiences
you will be exposed to.
Learning objectives
Content of the lecture
Independent learning from textbooks
Independent learning from the CD-ROM.
Independent learning from the Internet
Home Work
Problem-Based Learning
Self- Assessment (the answer to self-assessment exercises will be
discussed in tutorial sessions)
The main concepts
12
Faculty of Medicine
Biochemical Basis of Medicine I
Lectures
13
Faculty of Medicine
Biochemical Basis of Medicine I
Lectures # (1-3) :
Allosteric protein
Student Notes:
.
DEPARTMENT: Clinical Biochemistry
Tutor: Dr.
TEACHING LOCATION: Auditorium
By the end of this lecture, you will be able to:
1. Relate the structural properties of
particular
proteins
such
as
hemoglobin and myoglobin to their
functions in human health and
disease.
2. Discuss the genetic bases of protein
structure and how molecular defects
lead to diseases such as sickle cell
anemia.
3. Be able to recognize the structure of
the commonly found amino acids in
specific proteins and explain the
their importance.
• Hemoglobin:
• Quaternary structure of hemoglobin,
cooperative binding of oxygen, effect
of hydrogen ion and carbon dioxide
(Bohr effect)
• Functional significance of DPG, fetal
hemoglobin, abnormal hemoglobin,
(sickle cell anemia).
• Myoglobin:
• Globular proteins, myoglobin
configuration and conformation.
14
Faculty of Medicine
Biochemical Basis of Medicine I
• Oxygen binding site.
• Microenvironment and reversible
oxygen binding.
Myoglobin and hemoglobin are two
oxygen – binding proteins with a very
similar primary structure. However,
myoglobin is a globular protein
composed of a single polypeptide chain
that has one O2 binding site. Hemoglobin
is a tetramer composed of two different
types of subunits. Each subunit has a
strong sequence homology to myoglobin
and contains an O2 binding site. A
comparison between myoglobin and
hemoglobin illustrates some of the
advantages
of
a
multisubuniut
quaternary structure.
1. Required Texts And Resources: Lippincott
Illustrated Reviews, 3rd edition, Champe &
Harvey P : 25 - 42
2. Reading Handouts will be distributed
3- Lectures and power point presentation
will be published on department website:
www.kaau.edu.sa/faculties/medicine/dcbcweb
•
•
•
You have the opportunity to watch the CDROM about Hemoglobin. You can access the
CD-ROM during your spare time.
15
Faculty of Medicine
Biochemical Basis of Medicine I
1- Haemoglobin
http://www.ebi.ac.uk/interpro/potm/2005_10/Page1.h
2- Haemoglobin
http://www.iscid.org/encyclopedia/Haemoglobin
3- Haemoglobin animations
http://www.umass.edu/microbio/chime/hemoglob/2fr
t.htm
4- Oxygen dissociation curve
http://www.bio.davidson.edu/Courses/anphys/1999/D
s/Oxygendissociation.htm
5- Oxygen dissociation curve 2
http://www.ventworld.com/resources/oxydisso/dissoc
6- Haemoglobin dissociation curve 3
http://www.manbit.com/Hbdiss.htm
7- Carbon dioxide and Oxygen transport
http://cal.man.ac.uk/student_projects/2001/MNQC7N
omepage.htm
1- In a table form compare between
Hemoglobin
and
Myoglobin
including the difference in the :
Structure, Function, Oxygen binding
and Oxygen dissociation curve.
Clinical Question
A 67 – year old man presented to the
emergency department with one week history of
angina and shortness of breath. He complained
that his face and extremities had a "blue color" .
His medical history included chronic stable
angina trated with isosorbide dinitrate and
nitroglycerin. Blood obtained for analysis was
chocolate – colored. What is the possible
diagnosis
16
Faculty of Medicine
Biochemical Basis of Medicine I
I- Short Questions:
a- What of the effects of the following on
oxygen dissociation curve of Hemoglobin
1- 2,3 – BPG
2- CO2
3- pH
b- What is the molecular defect which leads
to the following?
1- Sickle cell disease
2- Methemoglobinemia
3- Thalassemias
II- MCQ:
1- Hemoglobin is
A. A tetramer of 4 myoglobin proteins.
B. A tetramer of four globin chains and one
heme prosthetic group.
C. A dimer of subunits each with two distinct
protein chains (alpha and beta).
D. A dimer of subunits each with two
myoglobin proteins.
2- Hydrophobic amino acid sequences in
myoglobin are responsible for
A. Covalent bonding to the heme prosthetic
group
B. The folding of the polypeptide chain
C. The reversible binding of oxygen
D. b and c above
3- Cooperative binding of oxygen by
hemoglobin
A. Is induced by hemoglobin
B. Is a result of different affinities for oxygen
by each subunit protein
C. Is induced by oxygenation
D. Is a result of interaction with myoglobin
17
Faculty of Medicine
Biochemical Basis of Medicine I
III- True / False
a. Proteins often consist of multiple
subunits so that they may have
different functions under different
conditions.
b. The porphyrin prosthetic group is
held into the interior of globin
molecules by covalent bonds to
specific amino acid residues
c. Myoglobin has a greater affinity
for oxygen than hemoglobin.
d. Cooperative
binding
and
allosterism of hemoglobin allow
oxygen to be unloaded at low
partial pressures of oxygen in the
tissues.
e. The Bohr effect is a description of
the effect of pH on hemoglobin,
oxygen bound more tightly at
f. low pH (in tissues) and less tightly
at higher pH values.
18
Faculty of Medicine
Biochemical Basis of Medicine I
Lecture #(4) :
Collagen
DEPARTMENT: Clinical Biochemistry
Tutor: Dr.
TEACHING LOCATION: Auditorium
By the end of this topic the student shall
be able to:
1. Understand the role of the
extracellular matrix
2. Understand the components of
the extracellular matrix
3. Understand the structure and
synthesis of collagen fibers
• Collagen.
• Synthesis
and
post-translational
modification of collagens.
• Noncollagenous
proteins
extracellular matrix.
in
the
Collagen is on of the components of
the extracellular matrix (ECM), which
present outside of the cell. This matrix,
even from a basic list of its components;
proteins, glycoproteins,
glycosaminoglycans, and many other
large and small biological molecules, can
19
Faculty of Medicine
Biochemical Basis of Medicine I
been seen as complex. Furthermore there
is no one specific ECM with great variation
from tissue to tissue and also specific
functional specializations. This lecture will
attempt therefore to only cover a Collagen
as a part of ECM.
1. Required Texts And Resources: Lippincott
Illustrated Reviews, 3rd edition, Champe &
Harvey P :
2. Reading Handouts will be distributed
3- Lectures and power point presentation
will be published on department website:
www.kaau.edu.sa/faculties/medicine/dcbcweb
•
•
•
You have the opportunity to watch the CDROM about Collagen You can access the CDROM during your spare time.
1-Extracellular matrix (Collagen)1
http://cellbiology.med.unsw.edu.au/units/science/l
e0508.htm
2 –Extracellular matrix (Collagen) 2
http://cellbiology.med.unsw.edu.au/units/pdf/anat
L8s4.pdf
3-Extracellular Matrix lecture
http://www.owlnet.rice.edu/~bioc341/notes/lec23.p
Do the proline side groups (rings) point
inward (to the center of the axis of the triple
helix), or do they point out? You can change
the "display" to "backbone" then back to
"sticks" to see where the side groups of
proline are.
20
Faculty of Medicine
Biochemical Basis of Medicine I
1- Explain how collagen structure
serves its function in different body
tissues
I- Short Questions:
1- How many amino acid chains are
present in this model of collagen?
2- Of the 20 possible amino acids, how
many are present in this model of
collagen?
3- What is the repeating pattern of these
amino acids?
II- MCQ:
1- Substitution of Gly in the primary
sequence of collagen with almost any other
amino acid results in defective collagen
assembly because:
A. collagen is glycosylated on Gly residues.
B. Gly forms critical hydrogen bonds with
neighboring glycines.
C. the contact points of the triple helix are
so close that only the Gly side chain fits
well into the space available.
D. Gly is crosslinked to allysine residues in
the mature protein.
2- The collagen defect present in scurvy is
A. substitution of gly for pro and lys
residues in the collagen sequence.
B. decreased protein stability due to
decreased hydroxylation of pro and lys
residues.
C. conversion of the collagen helix from a
right- to a left-handed triple supercoil.
D. decreased protein stability due to
increased glycosylation.
21
Faculty of Medicine
Biochemical Basis of Medicine I
III- True / False
a- Ascorbic acid is necessary for the formation
of hydroxyproline and hydroxylysine
residues before they are incorporated into
the collagen protein molecule.
b- All collagen types have a triple helical
structure.
c-
In Collagen molecules, Hydroxyproline
is formed by the posttranslational
hydroxylation of peptide-bound proline
residues catalyzed by the enzyme prolyl
transferase.
22
Faculty of Medicine
Biochemical Basis of Medicine I
LECTURE # (5) :
Introduction to the enzymes
DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this lecture you will be
able to:
1. Summarize the importance of
enzymes in many aspects in health
and disease
2. Describe general properties of
enzyme molecule and the process
of enzyme catalysis
3. Define terms used in enzymology
4. Compare and contrast between
enzymes and inorganic catalysts
5. Identify the nomenclature of
enzymes
6. Outline the classification of
enzymes
7. Distinguish the different types of
enzyme specificity
• Enzymes are important for medical
students
for
diagnosis
and
treatment
• Enzymes are typically large globular
proteins that accelerate reactions
by million folds
23
Student Notes:
.
Faculty of Medicine
Biochemical Basis of Medicine I
• Substrate, product, apoenzyme,
holoenzyme, cofactor, coenzyme,
active site and catalytic site, all are
terms used in study of enzymes
• There are many differences between
enzymes and inorganic catalysts as
reversibility and specificity of
enzyme action
• Naming of enzymes is either
convenient for everyday use, or
more complete systematic name
divided into six major classes
• Enzyme specificity are absolute,
relative, stereochemical and group
Remember that all reactions in the body are
mediated by enzymes, which are protein catalysts
that increase the rate of reactions without being
changed in the overall process. Enzymology is
important as inborn errors of metabolism are due
to deficiency of some enzymes. Also assay of
particular enzymes can help in diagnosis of many
diseases. The most striking characteristics of
enzymes are their catalytic power and specificity
which is of many types.
1. Required Texts And Resources: Lippincott
Illustrated Reviews, 3rd edition, Champe &
Harvey , chapter 27 ( pp:365-367)
2. Supplementary Texts And Resources:
Medical
Biochemistry,
Baynes
and
Dominiczek, 1st edition, Mosby. Chapter
18 (pp:217-218)
•
24
Faculty of Medicine
Biochemical Basis of Medicine I
•
•
You have the opportunity to watch the CDROM about enzymes. You can access the
CD-ROM during your spare time.
1- http://web.indstate.edu/thcme/mwkin
g/enzyme-kinetics.html
2- http://www.stolaf.edu/people/qiannin
i/fashanimat/enzymes
3- http://
www.reachoutmichigan.org/funexpe
riments/quick/eric/enzymes
4- http://www.pubmedcentral.nih.gov/a
rticlerender.fcgi?artid
5- http://www.ncbi.nlm.nih.ov/entrez/qu
ery/fcgi?cmd
6- http://www.wiley.com/legacy/college/
boyer/0470003790
7- http:/www.siu.edu/departments/bioc
hem/som_pbl/ms_ppt_anim.html
8- http://www.lewport.wnyric.org/wana
maker/animations/Enzymes%20activ
ity.
** Enzymes are biological catalysts that
accelerate the rate of reaction, by using
the library and the internet try to explain
how this occurs.
Clinical Case: A 52-year-old-man
presented at ER of a hospital
with severe chest pain which had
present for the past hour. He had
25
Faculty of Medicine
Biochemical Basis of Medicine I
a 2-year history of angina of
efforts.
How
can
you
use
enzymes in?:
a. Diagnosis of this case
b. Treatment of it
I- Short Questions:
1- Enumerate enzyme specificity
2- Differentiate between enzymes
and inorganic catalysts
II- MCQ:
1.Enzymes are:
a) Proteins
b) Chloroplasts
c) Genes
d) Mitochondria
2. Enzymes are catalysts. They increase the
rate of chemical reactions by:
a) Raising the activation energy
b) Temporarily increasing the temperature
c) Covalently binding the substrate
d) Lowering the activation energy
3. Enzymes are classified by the:
a) Size of the enzyme
b) Size of the substrate
c) Type of reaction
d) Rate of reaction
4. Shown below is a graph describing energy
versus reaction coordinate for a catalyzed
and uncatalyzed reaction. Fill in the blanks
with the letter that corresponds to each stage
of the graph.
26
Faculty of Medicine
Biochemical Basis of Medicine I
_____ ES
_____ S (substrate)
_____ P (product)
_____ Uncatalyzed reaction
III- Complete the following:
Some enzymes require another chemical to
function. These helper compounds are called
__________. If a cofactor is covalently bound to the
enzyme, it is called a __________ group. An
enzyme with its cofactor attached is called a
__________, while an enzyme minus its extra
component is called an __________.
27
Faculty of Medicine
Biochemical Basis of Medicine I
LECTURE # (6) :
Mechanism of enzymatic catalysis
DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this lecture you will be
able to:
1. Describe the two models of binding
the enzyme to its substrate
2. Identify what is meant by transition
state
3. Understand the difference between
∆G and ∆G‡
4. Explain the mechanism of enzymatic
catalysis by acid-base catalysis,
covalent catalysis, substrate strain
and entropy effect
• Two models have been proposed to
explain how an enzyme binds its
substrate; lock-and-key model and
induced-fit model
• Lock-and-key model assumes that
an enzyme active site will accept a
specific substrate
• Induced-fit model recognizes that
there is much flexibility in an
enzyme’s substrate . Accordingly,
an enzyme is able to conform to a
28
Student Notes:
.
Faculty of Medicine
Biochemical Basis of Medicine I
substrate
• Transition
state
is
state
of
maximum energy through which the
enzymatic reaction proceeds. It is
not an intermediate compound.
• The differences in free energy (∆G)
between the transition state and
substrate is the free energy of
activation (∆G‡)
• Enzyme can enhance the rate of
reaction
by
four
processes:
general/acid
base
catalysis,
covalent catalysis, substrate strain
and entropy effect
When correctly positioned and bound on the
enzyme surface, the substrate may be “strained”
toward the transition state. At this point the
substrate has been “set up” for acid-base and/or
covalent catalysis. Proper and the nearness of the
substrate with respect to the catalytic groups
(proximity effect) contribute to decrease in
entropy and so enhance the rate of enzymatic
reaction.
1. Required Texts And Resources: Lippincott
Illustrated Reviews, 3rd edition, Champe &
Harvey , chapter 27 ( pp:365-367)
2.Supplementary Texts And Resources:
Medical
Biochemistry,
Baynes
and
st
Dominiczek, 1 edition, Mosby. Chapter
18 (pp:217-218)
•
•
•
You have the opportunity to watch the CDROM about enzymes. You can access the
CD-ROM during your spare time.
29
Faculty of Medicine
Biochemical Basis of Medicine I
1http://web.indstate.edu/thcme/mwking/e
nzyme-kinetics.html
2http://www.stolaf.edu/people/qiannini/fash
animat/enzymes
3- http://
www.reachoutmichigan.org/funexperiment
s/quick/eric/enzymes
4http://www.pubmedcentral.nih.gov/articler
ender.fcgi?artid
5http://www.ncbi.nlm.nih.ov/entrez/query/
fcgi?cmd
6http://www.wiley.com/legacy/college/boy
er/0470003790
7http:/www.siu.edu/departments/biochem/s
om_pbl/ms_ppt_anim.html
8http://www.lewport.wnyric.org/wanamaker/
animations/Enzymes%20activity
9http://www.bio.winona.edu/berg/308/oldex
am/308exam1.txt
** How does the enzyme bind its
substrate?
By using the library and the internet
try to answer this question.
I- Short Questions:
1. What is meant by transition
state
30
Faculty of Medicine
Biochemical Basis of Medicine I
2. Enzymes can enhance the rate
of reaction. Enumerate the
processes by which this occurs.
II- MCQ:
1. The minimum amount of energy necessary
for a molecule(s) to react is the:
a) Activation energy
b) Free energy
c) Thermal energy
d) Potential energy
2. The state produced when two or more
molecules collide with just the right energy
and just the right orientation so that a
chemical reaction might occur is:
a) Catalytic state
b) Transition state
c) Activation state
d) Transient state
3. One of the following statement describing
the mechanism of enzyme action is
INCORRECT:
a) Many enzymes have flexible structures
that allow them to enfold their substrate
b) The substrate is often distorted when it
enters an enzyme-substrate complex
c) Amino acid side chains involved in the
formation of the active site center are
usually close together in the amino acid
sequence of the enzyme protein
d) Amino acid side chain near the active
site center often have a role in the catalytic
process
4.Which of the following statement about
enzyme catalyzed reaction is NOT TRUE:
a) Enzymes form complexes with their
substrate
b) Enzymes increase the activation energy
for chemical reaction
c) Many enzymes change shape slightly
when substrate binds
d) Reactions occur at the “active site” of
enzymes, where a precise quaternary
orientation of amino acids is an
important feature of catalysis
31
Faculty of Medicine
Biochemical Basis of Medicine I
III- Complete the following:
Enzymes carry out different chemical reactions in
catalysis. Fill in the blanks with the name of the
mechanism that matches with the example described
in each line. Mechanism names to choose from are:
covalent catalysis, acid-base catalysis, and metal ion
catalysis.
__________ catalysis may involve Glu, Asp, His, Lys,
or Arg residues.
__________ catalysis may involve Na+, K+ or Mg2+,
Ca2+.
__________ catalysis may involve serine proteases.
32
Faculty of Medicine
Biochemical Basis of Medicine I
LECTURE # (7) :
Enzyme kinetics
DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this lecture you will be able
to:
1. Distinguish the several terms used in
enzyme kinetics as rate or velocity,
rate constant, order of a reaction,
turnover number ..etc
2. Identify Michaelis-Menten equation
and Linweaver-Burk equation
3. Recognize the factors affecting
enzyme
activity
as
substrate
concentration, pH and temperature
• The enzyme (E) combines with its
substrate (S) to form an enzymesubstrate complex (ES).
• The ES complex can dissociate
again to form E + S, or can proceed
chemically to form E and the
product P.
• The rate constants k1, k2 and k3
describe the rates associated with
each step of the catalytic process.
33
Student Notes:
.
Faculty of Medicine
Biochemical Basis of Medicine I
• The initial velocity (Vo) at low
substrate concentration is directly
proportional to [S], while at high
substrate concentration the velocity
tends towards a maximum value
(Vmax) which is independent of [S].
• Michaelis-Menten
equation
describes a “hyperbolic curve” of
the relationship between [S] and
velocity of the reaction
• Lineweaver-Burk
plot
(double
reciprocal plot) gives a straight line
if Vo is measured at different
substrate concentration
• Not only substrate concentration ,
but also pH and temperature can
affect enzymatic activity
•
Kinetics is a study of the rate of changes of
substrates to products. Kinetics properties for many
enzymes reveals that, the rate of catalysis V varies
with [S] in a hyperbolic manner which is expressed in
Michaelis-Menten equation. Lineweaver-Burk plot
gives a straight line of relationship between [S] and
the rate of reaction..
1. Required Texts And Resources: Lippincott
Illustrated Reviews, 3rd edition, Champe &
Harvey , chapter 27 ( pp:365-367)
2. Supplementary Texts And Resources:
Medical
Biochemistry,
Baynes
and
Dominiczek, 1st edition, Mosby. Chapter
18 (pp:217-218)
•
•
•
You have the opportunity to watch the CDROM about enzymes. You can access the
CD-ROM during your spare time.
34
Faculty of Medicine
Biochemical Basis of Medicine I
1.http://web.indstate.edu/thcme/mwking
/enzyme-kinetics
2.htmlhttp://www.stolaf.edu/people/qian
nini/fashanimat/enzymes
3.http://
www.reachoutmichigan.org/funexperim
ents/quick/eric/enzymes
4.http://www.pubmedcentral.nih.gov/art
iclerender.fcgi?artid
5.http://www.ncbi.nlm.nih.ov/entrez/que
ry/fcgi?cmd
6.http://www.wiley.com/legacy/college/
boyer/0470003790
7.http:/www.siu.edu/departments/bioch
em/som_pbl/ms_ppt_anim.html
8.
http://www.lewport.wnyric.org/wanama
ker/animations/Enzymes%20activity.
By using the library and the internet
try to illustrate the relationship between
substrate concentration and reaction
velocity.
I- Short Questions:
a) Would you think that all enzyme
assays need the same pH? Why?
b) What is the meaning of optimum
temperature?
II- MCQ:
1. Which of the following does not influence
enzyme activity?
a) pH
b) Temperature
c) Product degradation
d) Substrate concentration
35
Faculty of Medicine
Biochemical Basis of Medicine I
2. The Michaelis constant Km is:
a) Numerically equal to ½ Vmax
b) Dependent on the enzyme concentration
c) Independent on pH
d) Numerically equal to the substrate
concentration that gives half-maximal velocity
What effect does temperature have on enzymes?
a) Boiling will denature them, as will being too
cold
b) Boiling will not harm them, but being too
cold will denature them
c) Boiling and cooling will both reduce the
speed of their rate
d) Boiling will denature them, but cooling will
only slow down their work
4. The Michaelis-Menten equation is Vo=Vmax
[S]/(Km+[S]).
Fill in the blanks with the letters shown to correctly
label each part of the graph
_____ Vmax
_____ [S]
_____ Vo
_____ Point used to determine the Km
III- Complete the following:
Often the kinetic values of an enzyme are
plotted using the Lineweaver-Burk
equation:
1/vo=Km/Vmax·1/[S]
+1/Vmax
Enter "yes" or "no" to indicate if the
equation and graphical terms match in each
statement.
_____
Y-intercept
and
-1/Km
_____
X-intercept
and
1/Vmax
_____ Slope and Km/Vmax
36
Faculty of Medicine
Biochemical Basis of Medicine I
LECTURE # (8) :
Enzyme inhibitors
DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this lecture you will be
able to:
1. Outline the importance of enzyme
inhibition studies
2. Discriminate the two broad classes of
enzyme inhibitors that based on the
extent of inhibition
3. Compare the mechanisms of enzyme
inhibition
4. Interpret the use of enzyme inhibition
as drugs in the treatment of diseases
• There are two broad classes of
enzyme inhibitors: reversible and
irreversible
• Reversible inhibitors interact with an
enzyme via noncovalent association
• Irreversible inhibitors interact with
an enzyme via covalent association
• Competitive inhibitors binds only to
enzyme (E) and not to enzymesubstrate complex (ES)
• Noncompetitive inhibitors binds
either to (E) and/or to (ES)
• Uncompetitive inhibitors binds only
37
Student Notes:
.
Faculty of Medicine
Biochemical Basis of Medicine I
to (ES) and not to (E)
• Enzyme inhibition may affect Vmax
or Km or both
• Many natural occurring and manmade compounds are irreversible
enzyme inhibitors
• There are therapeutic application for
enzyme inhibition
A competitive inhibitor prevents the substrate from
binding to its enzyme, while noncompetitive or
uncompetitive do not. Competitive inhibitor increases
Km without change Vmax. Noncompetitive inhibitor
decreases Vmax without change in Km. But
uncompetitive inhibitor decreases both Vmax and Km
.
1. Required Texts And Resources: Lippincott
Illustrated Reviews, 3rd edition, Champe &
Harvey , chapter 27 ( pp:365-367)
2. Supplementary Texts And Resources:
Medical
Biochemistry,
Baynes
and
st
Dominiczek, 1 edition, Mosby. Chapter
18 (pp:217-218)
•
•
•
You have the opportunity to watch the CDROM about enzymes. You can access the
CD-ROM during your spare time.
1http://web.indstate.edu/thcme/mwking/e
nzyme-kinetics.html
2http://www.stolaf.edu/people/qiannini/fa
38
Faculty of Medicine
Biochemical Basis of Medicine I
shanimat/enzymes
3- http://
www.reachoutmichigan.org/funexperime
nts/quick/eric/enzymes
4http://www.pubmedcentral.nih.gov/articl
erender.fcgi?artid
5http://www.ncbi.nlm.nih.ov/entrez/query/
fcgi?cmd
6http://www.wiley.com/legacy/college/boy
er/0470003790
7http:/www.siu.edu/departments/biochem
/som_pbl/ms_ppt_anim.html
8http://www.lewport.wnyric.org/wanamak
er/animations/Enzymes%20activity.
**How can the irreversible inhibitors
bind the active site of the enzyme?
By using the library and the internet
try to explain how this occurs.
Clinical Case: A young girl was
brought to the pediatric clinic with
infected wound on her knee. The
mother was instructed to give the
child penicillin. The child had
improved after a week.
a) What the possible mechanism
of action of this antibiotic?
b) What is the target enzyme of
penicillin?
I-
Short Questions:
1. Classify enzyme inhibitors
2. Tabulate the effect of competitive,
39
Faculty of Medicine
Biochemical Basis of Medicine I
noncompetitive and
uncompetitive on Vmax and Km
II- MCQ:
1. Which type of reversible enzyme inhibitor
binds to the free enzyme and the enzymesubstrate complex?
a) Noncompetititive
b) Competitive
c) Uncompetitive
d) None of the above
2. In competitive inhibition, one of the following
statement is CORRECT:
a) Vmax is increased
b) The concentration of active enzyme
molecule is unchanged
c) The apparent Km is increased
d) The apparent Km is decreased
3. Enzyme action can be influenced by the
presence of inhibitors. Which of the following
statements correctly matches the type of
inhibitor with its effect on an enzyme.
a) Irreversible and Renders the enzyme
permanently inactive
b) Competitive and Inhibitor binds only to
ES complex, only important when[S]
high, Vmax lower, Km lower
c) Noncompetitive and Can be overcome
with high [S], Vmax unchanged, Km higher
d) Uncompetitive and Cannot be overcome
with high[S], Vmax lower, but Km unchanged
4. In Lineweaver-Burk plot below:
a) Mention the type of inhibition of
enzymatic reaction
b) Which one of the lines of the plot
represents the enzymatic reaction
without inhibition?
40
Faculty of Medicine
Biochemical Basis of Medicine I
III- Complete the following:
Any molecule that acts directly on an
enzyme to lower its catalytic rate is
called ---------. Enzyme inhibition may
be
of
--------types.
Reversible
inhibition can be overcome by-----but
this is not possible for ----------inhibition.
41
Faculty of Medicine
Biochemical Basis of Medicine I
LECTURE # (9) :
Enzyme regulation
DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this lecture you will be
able to
1. Integrate enzymes into metabolic
pathways
2. Identify the terms of the rate-limiting
enzyme and the committed step in a
metabolic pathway
3. Know the different ways of enzyme
regulation under physiological and
pathological conditions
4. Recognize the allosteric regulation
5. Explain
a
feedback
control
mechanism
• There are key enzymes in a metabolic
pathway which can be regulated and
hence control the pathway
• The activity of these enzymes can be
regulated by:
• Changing the amount of enzyme by
enzyme induction, enzyme repression,
and enzyme degradation
• Changing the activity of enzyme by
allosteric regulation, feedback control,
42
Student Notes:
.
Faculty of Medicine
Biochemical Basis of Medicine I
covalent modification, and activation
by cleavage
• Compartmentation of pathways is also
a way of enzyme regulation
Control of a pathway occurs through modulation
of the activity of one or more key enzymes in the
pathway . The rate-limiting enzyme and the
committed step enzyme can be regulated by
changing the amount (enzyme induction, repression,
or degradation), or changing the activity (allosteric
regulation,
feedback
inhibition,
covalent
modification,
or
enzyme
cleavage)
or
compartmentation of the pathways.
1. Required Texts And Resources: Lippincott
Illustrated Reviews, 3rd edition, Champe &
Harvey , chapter 27 ( pp:365-367)
2. Supplementary Texts And Resources:
Medical
Biochemistry,
Baynes
and
Dominiczek, 1st edition, Mosby. Chapter
18 (pp:217-218)
•
•
•
You have the opportunity to watch the CDROM about enzymes. You can access the
CD-ROM during your spare time.
1http://web.indstate.edu/thcme/mwking/e
nzyme-kinetics.html
2http://www.stolaf.edu/people/qiannini/fa
shanimat/enzymes
3- http://
www.reachoutmichigan.org/funexperime
43
Faculty of Medicine
Biochemical Basis of Medicine I
nts/quick/eric/enzymes
4http://www.pubmedcentral.nih.gov/articl
erender.fcgi?artid
5http://www.ncbi.nlm.nih.ov/entrez/query/
fcgi?cmd
6http://www.wiley.com/legacy/college/boy
er/0470003790
7http:/www.siu.edu/departments/biochem
/som_pbl/ms_ppt_anim.html
8http://www.lewport.wnyric.org/wanamak
er/animations/Enzymes%20activity.
9- en.wikipedia.org/wik/Enzymes
10.www.elmhurst.edu/~chm/vchembook/
573 regulate
** By using the library and the internet
try to illustrate covalent modification of
an enzyme (e.g. glycogen phosphorylase)
II-
Short Questions:
1. List some of the molecular
mechanisms by which the
catalytic activity of enzymes is
controlled.
2. Using a graph, illustrate the
kinetic behavior of an allosteric
enzyme
II- MCQ:
1. Allosteric enzymes are large, oligomeric
proteins that have catalytic sites for binding
substrates and regulatory sites that bind
effectors. The separate oligomers influence
one another; they work cooperatively. This is
evidenced by the characteristic rate curves
for allosteric enzymes which have:
a) Michaelis-Menten kinetics
b) Hyperbolic kinetics
c) Sigmoidal kinetics
44
Faculty of Medicine
Biochemical Basis of Medicine I
d) Regulatory kinetics
2. Some enzymes are first synthesized in an
inactive form. These zymogens must undergo
proteolytic cleavage to produce the active
enzyme. Which of the following statements
are true of proteolytic cleavage?
a) It is reversible
b) It is irreversible
c) It is random
d) It occurs in the region of zymogen
synthesis
3. Increased synthesis of an enzyme is known
as:
a) Activation
b) Inhibition
c) Induction
d) Repression
4. In the graph below
a) Which one of the plot explains the
behavior of an allosteric enzyme?
b) What is the meaning of cooperativity?
III- Complete the following:
The rate- limiting enzyme in a pathway is the
enzyme with the-------Vmax, while the enzyme
catalyzing the committed step is -----------.
45
Faculty of Medicine
Biochemical Basis of Medicine I
LECTURE # (10) :
Coenzymes and cofactors
DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this lecture you will be
able to:
1. Recognize the importance of
cofactors and coenzymes for the
enzymes
2. Identify vitamin-derived coenzymes
3. Distinguish some coenzymes that are
synthesized
from
common
metabolites
4. Relate classes and groups of enzymes
to some coenzymes
• Cofactors are required by
inactive
apoenzymes
to
convert them into active
holoenzymes
• Cofactors may be metal ions
or
organic
compounds
(coenzymes)
• Coenzymes may be freely
dissociate from the enzyme, or
may remain bound to its
apoenzyme
• Metabolite coenzyme are Sadenosyl methionine, UDP46
Student Notes:
.
Faculty of Medicine
glucose
• Vitamin-derived
are NAD, NADP,
TPP, PLP, CoA
• Some coenzymes
from fat-soluble
vitamin K
Biochemical Basis of Medicine I
coenzymes
FAD, FMN,
are derived
vitamin as
Biological oxidation-reduction reactions need
certain hydrogen carriers as NAD, NADP, and FAD.
Some transaminases need PLP, transacylases need
CoA , transmethylases require SAM, and
transketolases need TPP.
Biotin is required for certain carboxylases, while THF
is needed for transfer of one carbon moiety. Vitamin K
is needed for carboxylation of glutamate residue in
prothrombin.
1. Required Texts And Resources: Lippincott
Illustrated Reviews, 3rd edition, Champe &
Harvey , chapter 27 ( pp:365-367)
2. Supplementary Texts And Resources:
Medical
Biochemistry,
Baynes
and
Dominiczek, 1st edition, Mosby. Chapter
18 (pp:217-218)
•
•
•
You have the opportunity to watch the CDROM about enzymes. You can access the
CD-ROM during your spare time.
47
Faculty of Medicine
Biochemical Basis of Medicine I
1http://web.indstate.edu/thcme/mwking/e
nzyme-kinetics.html
2http://www.stolaf.edu/people/qiannini/fa
shanimat/enzymes
3- http://
www.reachoutmichigan.org/funexperime
nts/quick/eric/enzymes
4http://www.pubmedcentral.nih.gov/articl
erender.fcgi?artid
5http://www.ncbi.nlm.nih.ov/entrez/query/
fcgi?cmd
6http://www.wiley.com/legacy/college/boy
er/0470003790
7http:/www.siu.edu/departments/biochem
/som_pbl/ms_ppt_anim.html
8http://www.lewport.wnyric.org/wanamak
er/animations/Enzymes%20activity.
** By using the library and the internet
try to illustrate the active part in each of
the following coenzymes: NAD, FAD,
TPP, CoA, PLP and THF
Clinical Case:
A 37-year-old man had
developed enlarged liver that
was tender to palpation. AST
in serum and total plasma
bilirubin were found to be
elevated.
A
diagnosis
of
48
Faculty of Medicine
Biochemical Basis of Medicine I
hepatitis was made.
a) What is the coenzyme
needed for AST?
b)
Mention
two
other
enzymes
that
need
this
coenzyme.
I- Short Questions:
1. Mention the coenzyme needed for
each of the following:
carboxylases, transaminases,
transmethylases, and transacyalses
2. Give examples of some metal ions
that are cofactors and mention the
enzyme of each.
II- MCQ:
1. Many enzymes require cofactors to function.
Many of these cofactors are vitamins.
Which of the following statements is NOT
TRUE?
a) Fe, Zn, Cu, Mg, Mn, K, and Mo are
classified as vitamins
b) Humans have lost the ability to
synthesize vitamins
c) Vitamins are modified by the body to
form coenzymes
d) There are two classes of vitamins:
water-soluble and fat-soluble
2. From which of the following vitamins, a
coenzyme of transketolases is derived ?:
a) Vitamin B1
b) Vitamin B2
c) Vitamin B6
d) Vitamin B12
3. A coenzyme derived from Niacin is:
a) FAD
b) NAD
c) CoASH
d) PLP
4. Shown below is a coenzyme acts as a
49
Faculty of Medicine
Biochemical Basis of Medicine I
hydrogen carrier
a) Give the full name of it
b) What is the name of the vitamin that is
derived from?
c) How can this coenzyme carry hydrogen
atoms?
III- Complete the following:
Some enzymes require another chemical to
function. These helper compounds are called
cofactors. Cofactors may be_____, or__________.
Examples of vitamin-derived coenzymes
are:_____,________, and________. Metabolitederived coenzymes include________and_________
50
Faculty of Medicine
Biochemical Basis of Medicine I
LECTURE # (11) :
Enzymes in clinical practice
DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this lecture you will be
able to:
1. Evaluate the use of enzymes and
isoenzymes in the diagnosis of
diseases
2. Know the use of enzymes in
treatment of some diseases
3. Recognize the ribozymes and
catalytic antibodies
4. Identify the site-directed mutagenesis
•
Enzymes are used clinically in three
principal ways:
- in diagnosis and prognosis of various
disease
- as analytical reagents in the
measurement of activity of other
enzyme or non-enzyme substances
- as therapeutic agents
•
RNA
enzymes
(hammerhead
ribozymes) and catalytic antibodies
are recently discovered
•
Site-directed mutagenesis is used for
design a new drug therapy
51
Student Notes:
.
Faculty of Medicine
Biochemical Basis of Medicine I
Isoenzymes are forms of an enzyme which are
structurally different but have similar catalytic
properties. Measurements of the isoenzymes of lactate
dehydrogenase (LDH), alkaline phosphatase (ALP),
and creatine kinase (CK) are of clinical value. Studies
have shown that catalysis for biochemical reactions
are not limited to naturally occurring proteins. Sitedirected mutagenesis (modification of amino acid
sequence of known enzymes) is used for design new
drug therapy.
1. Required Texts And Resources: Lippincott
Illustrated Reviews, 3rd edition, Champe &
Harvey , chapter 27 ( pp:365-367)
2. Supplementary Texts And Resources:
Medical
Biochemistry,
Baynes
and
Dominiczek, 1st edition, Mosby. Chapter
18 (pp:217-218)
•
•
•
You have the opportunity to watch the CDROM about enzymes. You can access the
CD-ROM during your spare time.
1http://web.indstate.edu/thcme/mwking/
enzyme-kinetics.html
2http://www.stolaf.edu/people/qiannini/f
ashanimat/enzymes
3- http://
52
Faculty of Medicine
Biochemical Basis of Medicine I
www.reachoutmichigan.org/funexperi
ments/quick/eric/enzymes
4http://www.pubmedcentral.nih.gov/arti
clerender.fcgi?artid
5http://www.ncbi.nlm.nih.ov/entrez/quer
y/fcgi?cmd
6http://www.wiley.com/legacy/college/b
oyer/0470003790
7http:/www.siu.edu/departments/bioche
m/som_pbl/ms_ppt_anim.html
8http://www.lewport.wnyric.org/wanama
ker/animations/Enzymes%20activity.
9www.dcnutrition.com/Miscellaneous/D
etail
**It was believed that all enzymes were
proteins till a recent discovery , by using
the library and the internet try to explain
this statement.
Clinical Case: A 52-year-old-man
presented at ER of a hospital with
severe chest pain which had
present for the past hour. He had a
2-year history of angina of efforts.
a) What specific tests would you
request from the biochemistry
laboratory?
b) How can use of an enzyme
share in the treatment of this
condition?
I- Short Questions:
53
Faculty of Medicine
Biochemical Basis of Medicine I
1. Enumerate five enzymes used in
clinical diagnosis and mention
the major diagnostic use for
each
2. What are the causes of presence
of non-plasma specific
enzymes?
II- MCQ:
1. In normal blood, the alkaline phosphatase activ
mainly from:
a) Bone and small intestine
b) Bone and liver
c) Small intestine and placenta
d) Bone and placenta
2. How many different isoenzymes of normal
LDH can be identified by electrophoresis at pH 8.6
a) Two
b) Three
c) Four
d) Five
3. LDH assays are useful in diagnosing diseases
of the:
a) Heart
b) Pancreas
c) Liver
d) a and c
54
Faculty of Medicine
Biochemical Basis of Medicine I
Lectures # ( 12 ) :
Membrane Structure
DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this topic the you will be
able to:
1. Comprehend the fluid mosaic
model of biologic membrane.
2. Understand how change in
membrane composition changes
its function.
Chemical compositions of membranes:
•
Separation of cells and intracellular
organells into different chemical
compartments by membranes.
•
Lipids of membranes.
•
Distribution of membrane lipids.
•
Membrane proteins.
•
Carbohydrates of membranes.
Molecular structure of membranes:
•
The fluid mosaic model of biologic
membranes.
•
Asymmetry of membrane.Membrane
fluidity
55
Faculty of Medicine
Biochemical Basis of Medicine I
Membranes are highly viscous, plastic
structures. Plasma membranes form
closed compartments around cellular
protoplasm to separate one cell from
another and thus permit cellular
individuality. The plasma membrane has
selective permeabilities and acts as a
barrier, thereby maintaining differences
in composition between the inside and
outside of the cell.
1. Required Texts And Resources: Lippincott
Illustrated Reviews, 3rd edition, Champe &
Harvey P :
2. Reading Handouts will be distributed
3- Lectures and power point presentation
will be published on department website:
www.kaau.edu.sa/faculties/medicine/dcbcweb
•
•
•
You have the opportunity to watch the CDROM about Membrane structure. You can
access the CD-ROM during your spare time.
1- Membrane structure
http://cellbio.utmb.edu/cellbio/membrane.htm
2- Biological membrane structure
http://www.pnas.org/cgi/content/abstract/66/3/615
3- Biological membrane structure
http://www.pnas.org/cgi/content/abstract/66/3/615
4- Membrane Composition
http://www.pnas.org/cgi/content/abstract/66/3/615
56
Faculty of Medicine
Biochemical Basis of Medicine I
1- Draw a figure for cell membrane,
mention the basic composition for the
membrane and explain how membrane
structure serves its function?
I- Short Questions:
a- Which component (s) of membranes give
it its fluid characteristics?
b- Which part of a membrane helps it keep
its shape (prevents deformation)?
c- How are proteins arranged in a
membrane? What is the difference between
a transmembrane protein and a peripheral
membrane protein?
d- What feature in a membrane helps to
prevent freezing? Be specific.
II- MCQ:
1- Triacylglycerols cannot form lipid bilayers
because they
A.
B.
C.
D.
Have hydrophobic tails
Do not have polar heads
Cannot associate with cholesterol
Have polar heads
2- In a typical eukaryotic plasma membrane
A. Proteins can move in and out of the
bilayer
B. Lipids can move and diffuse through the
bilayer
C. Some lipids can rotate within the bilayer
D. All of the above
3- The arrangement of lipid bilayers and other
components is the basis for the currently
widely accepted description which is called the
A. Lipid bilayer model
B. Mosaic model
C. Diffusion model
D. Fluid mosaic model
III- True / False
57
Faculty of Medicine
Biochemical Basis of Medicine I
A. According to the current model of cell
membrane structure, the two layers of
lipids in the bilayer are nearly identical
B. Cholesterol accounts for 20% to 25% of
the mass of lipids in a typical
mammalian plasma membrane
C. The
distribution
of
peripheral
membrane proteins is generally identical
on both sides of a given membrane.
58
Faculty of Medicine
Biochemical Basis of Medicine I
Lectures #(13) :
Membrane Transport
DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this topic you will be able
to:
1. Explain how molecules move through
membranes and the forms of energy
needed to derive this process and to
differentiate between active and
passive transport.
2. Appreciate the functional role of
membrane proteins as pumps, gates,
channels and receptors.
Movement of molecules across
membranes:
• Diffusion
across
cellular
membranes.
• Mediated
transport
passive
mediated transport system, active
mediated transport system: Na+
K+.
• ATpase, Ca2+ translocation and
Na+ dependent transport system.
• Endocytosis and phagocytosis
59
Student Notes:
.
Faculty of Medicine
Biochemical Basis of Medicine I
Molecules can passively traverse the
lipid bilayer of the membranes down
electrochemical gradients by simple
diffusion or by facilitated diffusion. This
spontaneous
movement
toward
equilibrium contrasts with active
transport, which requires energy because
it constitutes movement against an
electrochemical gradient.
1. Required Texts And Resources: Lippincott
Illustrated Reviews, 3rd edition, Champe &
Harvey P :
2. Reading Handouts will be distributed
3- Lectures and power point presentation
will be published on department website:
www.kaau.edu.sa/faculties/medicine/dcbcweb
•
•
•
You have the opportunity to watch the CDROM about Membrane transport. You can
access the CD-ROM during your spare time.
1-Membrane transport 1
http://www.emc.maricopa.edu/faculty/farabee/bio
ioBooktransp.html
2-Transport across cell membrane
http://users.rcn.com/jkimball.ma.ultranet/Biology
s/D/Diffusion.html
3-Membrane transport mechanisms
http://physioweb.med.uvm.edu/bodyfluids/membr
htm
4- Cell membrane and transport mechanisms
http://staff.jccc.net/PDECELL/cells/transport.htm
60
Faculty of Medicine
Biochemical Basis of Medicine I
1- In a table form, describe Major
mechanisms used to transfer material,
mention the characteristics of each of
them including the factor affecting and
the need for energy.
I- Short Questions:
1- Give the definition for the following:
a- Simple diffusion
b- Facilitated diffusion
c- Uniport, antiport, symport
d- Active transport
e- Endocytosis
II- MCQ:
1- Very large molecules (macromolecules)
can be transported across membranes by :
E. pores or channels with very large
openings through the center
F. active transport proteins
G. diffusion down a concentration gradient
H. endocytosis or exocytosis
2- Another name for facilitated diffusion is
E. Active transport
F. Transverse diffusion
G. Lateral diffusion
H. Passive transport
3- Facilitated diffusion (passive transport)
through a biological membrane is:
A. generally irreversible
B. driven by the ATP to ADP conversion
C. driven by a concentration gradient
D. endergonic
61
Faculty of Medicine
Biochemical Basis of Medicine I
III- True / False
a- Proteins that transport water across cell
membranes are called aquaporins.
b- Symport and antiport proteins must be
active transport proteins.
c- Active transport involves the conversion of
ADP to ATP.
d- Endocytosis is the process by which cells
take up large molecules
e- In adipocytes and muscle, glucose enters by
facilitated diffusion
62
Faculty of Medicine
Biochemical Basis of Medicine I
Lectures #(14) :
Cellular transduction
DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this topic you will be able
to:
1. The molecular mechanisms for regulation
and action of protein kinases, protein
phosphatases and G-proteins including
small G- proteins of the Ras-superfamily
and heterotrimeric G-proteins;
2. The molecular basis for signalling by
reversible protein phosphorylation;
3. The molecular basis for targeting in signal
transduction.
• Kinases & phosphatases
• Protein Kinase A (cAMPdependent protein kinase)
• G-protein signal cascade
• Structure of G-proteins
• Small GTP-binding proteins,
GAPs & GEFs
• Phosphatidylinositol
signal
cascades
• Signal protein complexes
63
Faculty of Medicine
Biochemical Basis of Medicine I
Cellular transduction is any process
by which a cell converts one kind
of signal or stimulus into another.
Processes referred to as signal
transduction often involve a
sequence of biochemical reactions
inside the cell, which are carried
out by enzymes and linked through
second messengers. Such processes
take place in as little time as a
millisecond or as long as a few
seconds.
1. Required Texts And Resources: Lippincott
Illustrated Reviews, 3rd edition, Champe &
Harvey P :
2. Reading Handouts will be distributed
3- Lectures and power point presentation
will be published on department website:
www.kaau.edu.sa/faculties/medicine/dcbcweb
•
•
•
You have the opportunity to watch the CDROM about Cellular transduction. You can
access the CD-ROM during your spare time.
1-Signal transduction power point presentation
www.smd.qmul.ac.uk/morbidanatomy/Cancerbiolo
gy/Cancer-Signal-transduction.ppt
2-Signal transduction lecture powerpoint 2
www.nida.nih.gov/whatsnew/meetings/frontiers/po
werpoint/howlett.ppt
3-Signal transduction lecture powerpoint 3
64
Faculty of Medicine
Biochemical Basis of Medicine I
www.bmb.psu.edu/courses/bmmb598e/signaltrans.
pdf 4- Signal transduction in tumor cells
www.mdc-berlin.de/signaltransduction
1- Diagram and describe the sequence of
events by which a hormone such as
epinephrine or glucagon activates
production of cyclic AMP within a cell.
Include the roles of the receptor (GPCR),
the different subunits of the stimulatory G
protein, and Adenylate Cyclase. How is the
signal turned off at each step? You may be
asked to briefly describe the role of one of
the following: AKAP, RGS protein.
2- Describe the activation of cAMPDependent Protein Kinase. What causes the
enzyme to be inhibited in the absence of
cyclic AMP? How is activation by cyclic
AMP turned off?
Signaling pathways are a balance of positive
and negative signals. Cholera toxin, the
active agent of Cholera vibrio, causes an
increase in protein kinase A activity. From
this point of view, Explain how cholera
toxins produces its toxic effects?
I- Short Questions:
1- Diagram an example of the reaction
catalyzed by the activated cAMPDependent Protein Kinase. What reaction is
catalyzed by the enzyme Protein
Phosphatase.
65
Faculty of Medicine
Biochemical Basis of Medicine I
2- Write out (in words) the reaction
catalyzed by Phospholipase C. Describe the
"second messenger" roles of the two
products of the Phospholipase C reaction.
II- MCQ:
1- In signal transduction what is an effector
enzyme?
A. An integral membrane protein that changes
conformation upon binding of a ligand to a cell
surface receptor.
B.A small molecule that diffuses within a cell and
carries a signal to its ultimate destination.
C.A protein bound on the interior of a cell
membrane that generates a second messenger.
D.Protein bound on the exterior surface of a cell
and is the receptor site for a ligand.
2- Which does not generally use a signal
transduction mechanism?
A.hydrophilic hormones
B.neurotransmitters
C.growth factors
D.steroids
3- Which of the following enzymes is
involved in the activation of the protein
kinase C signaling pathway?
A- Ca2+-ATPase
B.Gβγ
C.phospholipase C
D. DAG kinase
III- True / False
a- G proteins are are multisubunit proteins
consisting of , and subunits
b- In the adenyl cyclase signaling pathway the
second messenger is AMP
c- The toxins from cholera and whooping
cough both interfere with the proper
functioning of ATP synthesis.
66
Faculty of Medicine
Biochemical Basis of Medicine I
LECTURE # (15- 16 ):
Introduction to Metabolism, Bioenergetics, and the
Role of ATP
Student Notes:
DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this lecture, you will be
able to:
1. Compare and contrast catabolism
and anabolism
2. Outline the general mechanisms
for regulating metabolic pathways
through enzymes.
3. Understand the role of ADP/ATP
in connecting catabolic and
anabolic reactions. How does the
structure of these molecules
allow them to mediate energy
requiring reactions?
4. Compare the two physiological
mechanisms for the net synthesis
of ATP
5. Be able to determine the direction
in which electrons would pass in
an oxidation-reduction couple,
given either ΔG’ or ΔE’.
6. Be familiar with the relative
oxidation reduction potentials of
NAD, FAD (FMN), ubiquinone,
cytochromes c and a, and
oxygen.
7. Understand the importance of
various
mitochondrial
compartments in cellular energy
production.
8. Explain the relationship between
67
.
Faculty of Medicine
Biochemical Basis of Medicine I
electron flow and ATP production
in
the
mitochondria
(chemiosmotic theory of Peter
Mitchell).
9. Describe the components of the
electron transport chain, including
the points where common
inhibitors act.
10. Discuss the mechanism of
ATP
production
in
the
mitochondria.
11. Understand the concepts of
respiratory control and coupling.
• Metabolic Pathways
1- Definition, classification
(Anabolism &
Catabolism)
2- Catabolic phase
3- Low and high energy
bonds – ATP – ADP
cycle
4- Mechanism of
collection of energy
• Regulation of Metabolism
1- Signals from within the
cells
2- Communication
between cells
3- Intracellular messenger
systems
• Electron transport chain (ETC)
1- Components of ETC
2- Electron transport
3- Chemiosmotic
hypothesis
4- ATP synthesis
5- Inhibition of ETC
6- Uncouplers
68
Faculty of Medicine
Biochemical Basis of Medicine I
In order to survive, humans must
meet two basic metabolic requirements:
we must be able to synthesize everything
our cells need that is not supplied by our
diet, and we must be able to protect our
internal environment. In order to meet
these requirements, we metabolize our
dietary components through four basic
types of pathways: Fuel oxidative
pathways, fuel storage and mobalization
pathways, biosynthetic pathways, and
detoxification or waste disposal pathways.
1- Required Texts And Resources:
Lippincott Illustrated Reviews, 3rd
edition, Champe & Harvey P: 69 – 82 &
P: 89 - 94
2. Reading Handouts will be
distributed
3- Lectures and power point
presentation will be published on
department website:
www.kaau.edu.sa/faculties/medicine/
dcbcweb
•
•
•
You have the opportunity to watch the CDROM about Bioenergetics and introduction
to metabolism . You can access the CDROM during your spare time.
1- Overview of metabolism
http://www.elmhurst.edu/~chm/vchembook/5900verviewmet
.html
2- Introduction to metabolism (PowerPoint)
http://www.rit.edu/~pac8612/Biochemistry/503(703)/ppt/Intr
69
Faculty of Medicine
Biochemical Basis of Medicine I
oduction_to_Metabolism.ppt
3- Electro Transport chain(ECT)
http://www.dentistry.leeds.ac.uk/biochem/lecture/etran/etra
n.htm
4- Electro Transport chain(ECT)
http://vcell.ndsu.nodak.edu/animations/etc/movie.htm
5- ECT Animation
http://www.sp.uconn.edu/~terry/images/anim/ETS_slo
w.html
6- ATP Synthesis Animation
http://www.sp.uconn.edu/~terry/images/anim/ATPmit
o.html
7- ECT Movie
http://vcell.ndsu.nodak.edu/animations/etc/movie.htm
1- Regulation of metabolism is
based on need, from your studying
outline the factors regulating
metabolism and how they work
according to body needs?
2- Summarize the composition of
each of the respiratory chain
complexes I, III, and IV. Diagram the
pathway of electron transfer in the
mitochondrial inner membrane from
matrix NADH to oxygen, including
the smaller electron carriers,
coenzyme Q and cytochrome?
1- If sodium ions rather than
protons were pumped across
the mitochondrial membrane,
would there be any energy
available to couple to ATP
synthesis?
2- Clinical Question
The desire for a quick weightloss drug has led to a number
of disasters. In the 1930s,
dinitrophenol was explored as
a possible weight-loss aid, but
it had a variety of severe side
effects, including
70
Faculty of Medicine
Biochemical Basis of Medicine I
hyperthermia and death. Why
was dinitrophenol a bad idea?
Explain how dinitrophenol
induces hyperthermia
I- Short Questions:
1- Give the definition for the
following:
a- Anabolic reaction
b- Catabolic reaction
c- Free Energy Change
d- Electron Transport Chain
2. Enumerate components of Electron
Transport Chain, How many ATP
molecules will be produced from
oxidation of One NADH+H+,
FADH2 respectively, in the chain?
3-
How cAMP activates some
metabolic reactions and inhibits
others?
II- MCQ:
1. In the mitochondria NADH and QH2 are
oxidized by ____________.
(a) carbon dioxide
(b) hydrogen peroxide
(c) ozone
(d) oxygen
2. The synthesis of one molecule of ATP
from ADP requires _________ to be
translocated across the inner mitochondrial
membrane.
(a) one proton
(b) about two protons
(c) hundreds of protons
(d) 1 mole of protons
71
Faculty of Medicine
Biochemical Basis of Medicine I
3. The degradation of which class of
biochemicals
does
not
significantly
contribute to the release of
energy to cells?
(a) nucleic acids
(b) Proteins
(c) Lipids
(d) carbohydrates
III- True / False
a. The biochemical reactions that
degrade molecules, such as
nutrients, are called anabolic
reactions
b. Metabolic pathways generally
have
easily
distinguished
starting and stopping points
c. All metabolic reactions occur in
the cytosol of cells
d. In
mammals
the
enzyme
complexes
of
oxidative
phosphorylation are in the inner
mitochondrial
e. Most of the free energy needed
to drive ATP formation in the
mitochondria is the result of an
electrical contribution from a
charge gradient across the
inner mitochondrial membrane
matrix.
72
Faculty of Medicine
Biochemical Basis of Medicine I
LECTURE # (17- 18)
Glycolysis
DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this lecture you will
be able to:
1- Define glycolysis, form a working
definition knowing the substrates
and products involved and any
other key intermediates produced.
2- Trace
tissue
location
of
glycolysis, particularly tissues or
cells in the body where the
pathway is most important.
3- Locate the cell site of glycolysis,
where in the cell it occurs
(cytosol).
4- Describe the sequence of events,
the overall reaction sequence and
the number of stages and
reactions:
a. Material Flow:: Trace the
fate of labeled carbon or
other elements through the
pathway
b. Energy flow: Trace
the
production and consumption
of ATP
73
:
Student Notes:
.
Faculty of Medicine
Biochemical Basis of Medicine I
c. Electron flow: trace the
production and consumption
of reducing power
5- Identify the Key steps, either
those which form major control
sites or those which are main "
branch points"
6- Describe connections to other
pathways especially citric acid
cycle .
•
•
•
•
•
Overview of Glycolysis
Coupled Reactions in Glycolysis
First Phase of Glycolysis
Second Phase of Glycolysis
Metabolic Fates of NADH and
Pyruvate
• Anaerobic Pathways for Pyruvate
• Energetic Elegance of Glycolysis
• Other Substrates in Glycolysis
The glycolytic pathway is employed by all
tissues for the breakdown of glucose to
provide energy ( in the form of ATP) and
intermediates
for
other
metabolic
pathways.
1.
Required Texts And Resources:
Lippincott Illustrated Reviews, 3rd
edition, Champe & Harvey
2. Supplementary Texts And Resources:
Medical Biochemistry, Baynes and
Dominiczek, 1st edition, Mosby
74
Faculty of Medicine
Biochemical Basis of Medicine I
•
•
•
You have the opportunity to watch the CDROM about glycolysis. You can access
the CD-ROM during your spare time.
1. Introduction to Glycolysis:
http://www.terravivida.com/vivida/glyin
2. Glycolysis Lecture:
http://web.indstate.edu/thcme/mwking
olysis.html
3. Glycolysis Animation:
http://www.johnkyrk.com/glycolysis.ht
4. Glycolysis Home:
http://biotech.icmb.utexas.edu/glyco
lysis/glycohome.html
3- List the enzymes that convert glucose
to glyceraldehyde 3-PO4. Add to your
list the substrates, products, and
cofactors for each of these enzymes. It
might be handy to make up a table
for this.
4- List the enzymes that convert
glyceraldehyde 3-PO4 to pyruvate.
Add to your list the substrates,
products, and cofactors for each of
these enzymes. It might be handy to
make up another table for this.
2- Clinical Question
Predict the effect of a GLUT4
knockout (in mice) on the levels
75
Faculty of Medicine
Biochemical Basis of Medicine I
of blood glucose before and after
a meal. Search the Internet and
report whether your predictions
were confirmed by experiment.
Of what use is a GLUT4 knockout
mouse?
3- Clinical Case
Ahmed entered the stadium
for the final lap of his
marathon race. He was well
ahead of his competitors. In
the last few minutes, he
became confused. In the
stadium, he started running
around the track in the wrong
direction and then collapsed.
What went wrong?
I- Short Questions:
1- Give the cellular location of the
glycolytic pathway.
2- Where is NADH produced ?
3. Which step produces ATP? Which
one of these is considered to be
'substrate level phosphorylation?
4- Name the enzyme that makes
anaerobic glycolysis possible by
using up the NADH that
accumulates.
5 -Consider
the ten steps of glycolysis,
starting with glucose. What would
be the effect on pyruvate
concentration (increase, decrease
or none) of increasing the
concentration of the following?
Give a brief (one sentence)
explanation for your answer.
a) ATP
76
Faculty of Medicine
Biochemical Basis of Medicine I
b) AMP
c) citrate
d) fructose-1,6-bisphosphate
e) fructose-2,6-bisphosphate
II- MCQ:
1- Which of the following
metabolites does not regulate
glycolysis in liver cells?
A. glucose-6-phosphate
B. fructose-6-phosphate
C. fructose-1-phosphate
D. fructose-2,6-bisphosphate
2-During kinase reactions, the role
of magnesium ions is to
A. be catalytic metals at the active sites
of the enzymes.
B. interact with the hydroxyl groups of
the various sugar molecules.
C. interact with the negative charges on
phosphate groups.
D. provide a bridging atom between
substrate and product, stabilizing
the transition state.
3- Which of the following is not a
substrate for hexokinase?
A. glucose
B. fructose
C. galactose
D. mannose
3- How many ATP molecules are
produced from glucose during
anaerobic glycolysis?
A. 0
B. 1
C. 2
77
Faculty of Medicine
Biochemical Basis of Medicine I
D. 3
III- True / False
a. Four molecules of ATP are
consumed per glucose
during the hexose stage
of glycolysis
b. The reaction catalyzed by
PFK-1
is
metabolically
reversible
c. Mammals
can
convert
pyruvate to either ethanol
or lactate depending on
the availability of oxygen
d. Glucose
is
normally
transported into cells by
an
active
transport
protein
since
the
concentration of glucose
inside cells is normally
higher than that in the
blood.
e. Two molecules of ATP are
consumed per glucose
molecule during the
hexose stage of glycolysis
78
Faculty of Medicine
Biochemical Basis of Medicine I
LECTURE # (19) :
Tricarboxylic Acid Cycle (TCA)
DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this lecture you will
be able to:
1. Define
TCA, form a working
definition knowing the substrates
and products involved and any
other key intermediates produced.
2. Trace tissue location of TCA,
particularly tissues or cells in the
body where the pathway is most
important.
3. Locate the cell site of TCA, where
in the cell it occurs (Mitochondria).
4. Describe the sequence of events,
the overall reaction sequence and
the number of stages and reactions:
a- Material Flow:: Trace the fate of
labeled carbon or other elements
through the pathway
b- Energy flow: Trace the production
and consumption of ATP
c- Electron flow: trace the production
and consumption of reducing
power
5. Identify the Key steps, either those
which form major control sites or
those which are main " branch
points"
79
Student Notes:
.
Faculty of Medicine
Biochemical Basis of Medicine I
6. Describe connections to other
pathways related to carbohydrate,
lipid and amino acids metabolism
7. Describe the amphibolic aspects of
TCA and the role of its
intermediate in various metabolic
process.
8. Diagram the shuttles for the transport
of cytoplasmic reducing equivalents
into the mitochondria
• Overview of TCA
• Reaction of the TCA cycle
a- Oxidative decarboxylation
of pyruvate
b- The eight sequential
reactions of TCA
• Energy produced by the cycle
• Regulation of the TCA cycle
The tricarboxylic acid cycle (TCA) is
also called citric acid cycle or Kreb's cycle.
It is the major final common pathway of
oxidation of carbohydrates, lipids and
proteins since their oxidations yield Acetyl
Co A. It also plays a major role in
lipogenesis,gluconeogenesis,
transamination and deamination.
1.
Required Texts And Resources:
Lippincott Illustrated Reviews, 3rd
edition, Champe & Harvey P: 107 – 114
80
Faculty of Medicine
Biochemical Basis of Medicine I
2. Supplementary Texts And Resources:
Medical Biochemistry, Baynes and
Dominiczek, 1st edition, Mosby
You have the opportunity to watch the CDROM about TCA. You can access the CDROM during your spare time.
1- TCA animation
http://www.science.smith.edu/departments/Biol
Bio231/krebs.html
2-TCA animation
http://www.wiley.com/legacy/college/boyer/0470
90/animations/tca/tca.htm
3- TCA
http://www.sigmaaldrich.com/Area_of_Interest/L
Science/Metabolomics/Key_Resources/Meta
_Pathways/TCA_Cycle.html
4- Step by step Kreb’s cycle
http://www.terravivida.com/vivida/tcasteps/
5- Biochemistry animations
http://www.wiley.com/college/fob/anim/
a. Diagram the Krebs Citric Acid Cycle,
beginning with pyruvate, giving the
names of all enzyme substrates and
products and names of enzymes (no
abbreviations). Indicate where NAD+,
NADH, FAD, FADH2, GDP, Pi, GTP,
coenzyme A, H2O, or CO2 are
substrates or products of reactions.
81
Faculty of Medicine
Biochemical Basis of Medicine I
b. What is the fate of reducing equivalents
of FADH2 generated in Krebs Cycle?
1- Clinical Question
A patient diagnosed with
thiamine deficiency exhibited
fatigue and muscle cramps.
The muscle cramps have been
related to an accumulation of
metabolic acid. What is the
metabolic product leads to this
condition? Explain your
answer.
I- Short Questions:
1- What is the intercellular location of
TCA?
2- What is the sources of Acetyl
CoA?
3- What are the products of TCA?
4- Describe the functions of 2
intermediates of TCA?
5- Summarize the functions of TCA.
II- MCQ:
1- The citric acid cycle oxidizes
pyruvate and some of the pathway
intermediates are starting
materials for many biosynthetic
pathways. This means the citric
acid cycle is a/an
______________.
A.
B.
C.
D.
amplifying pathway
strictly catabolic pathway
anaerobic pathway
amphibolic pathway
82
Faculty of Medicine
Biochemical Basis of Medicine I
2- In eukaryotes the enzymes of
the citric acid cycle are found in the
_________.
A. cytosol
B. mitochondria
C. nucleus
D. endoplasmic reticulum
3- The enzyme pyruvate
translocase is located
______________.
A. in the cytosol
B.in the inner mitochondrial
membrane
C. in the mitochondrial matrix
D. in the endoplasmic reticulum
III- True / False
1- The overall goal of the citric
acid cycle is to oxidize
pyruvate, form reduced
coenzymes and produce ATP
2- The citric acid cycle is an
anaerobic pathway that occurs
in the mitochondria of
eukaryotes.
3- ATP is consumed by the
pyruvate dehydrogenase
complex during the synthesis
of acetyl CoA
4- The citric acid cycle can be
viewed as a multi-step catalyst
simply because it returns to its
original state after each round
of reactions.
5- Isocitrate is more easily
oxidized than citrate because
it has a secondary alcohol
group, whereas citrate's
alcohol group is tertiary
83
Faculty of Medicine
Biochemical Basis of Medicine I
LECTURE # (20) :
Gluconeogenesis
D DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this lecture you will be
able to:
1- Define Gluconeogenesis, form a
working definition knowing the
substrates and products involved
and any other key intermediates
produced.
2- Trace
tissue
location
of
gluconeogenesis,
particularly
tissues or cells in the body where
the pathway is most important.
3- Locate
the
cell
site
of
gluconeogenesis, where in the cell
it occurs (cytosol) Except for the
carboxylation of pyruvate, which
occurs in mitochondria.
4- Describe the sequence of events,
the overall reaction sequence and
the number of stages and reactions:
a. Material Flow:: Trace the fate of
labeled carbon or other elements
through the pathway
b. Energy flow: Trace the production
and consumption of ATP
c. Electron flow: trace the production
and consumption of reducing
84
Student Notes:
.
Faculty of Medicine
Biochemical Basis of Medicine I
power
5- Describe the sequence of events,
the overall reaction sequence and
the number of stages and reactions
6- Identify the Key steps, either those
which form major control sites or
those which are main " branch
points"
7- Describe connections to other
pathways, especially glycolysis and
the reciprocal regulation of both
pathway
8- Identify the non carbohydrate
sources of gluconeogenesis.
• Overview of gluconeogenesis
• Substrates for gluconeogenesis
• Reactions unique to
gluconeogenesis
• Regulation of gluconeogenesis
Gluconeogenesis is ' production of
glucose from non – carbohydrate sources'
For a period of starvation of longer than
about 12 hours. This pathway is very
important for tissues which require a
continuous supply of glucose as a
metabolic fuel such as the brain, red
blood cells, kidney medulla, lens and
cornea of the eye, testes and exercising
muscle.
85
Faculty of Medicine
Biochemical Basis of Medicine I
1.
Required Texts And Resources:
Lippincott Illustrated Reviews, 3rd
edition, Champe & Harvey p: 115 - 122
2. Supplementary Texts And Resources:
Medical Biochemistry, Baynes and
Dominiczek, 1st edition, Mosby
•
•
•
You have the opportunity to watch the CDROM about gluconeogenessis. You can
access the CD-ROM during your spare
time.
1- Gluconeogenesis
http://web.indstate.edu/thcme/mwking/gluconeogenesi
s.html
2- Gluconeogenesis
http://www.answers.com/topic/gluconeogenesis
3- Gluconeogenesis animation
http://www.wiley.com/college/fob/quiz/quiz15/1522.html
4- Gluconeogenesis powerpoint presentation
http://www.sb.fsu.edu/~chapman/Classes/Bch4054/Co
ntent/Gluconeogenesis.pdf
1. a. Write out the two sequential
reactions
catalyzed
by
Pyruvate
Carboxylase,
giving
names
and
structures of reactants and products,
including the active site prosthetic
group. What is the nature and
significance of the linkage of the
prosthetic group to the Pyruvate
Carboxylase enzyme?
86
Faculty of Medicine
Biochemical Basis of Medicine I
b. Describe and explain the significance
of the effect of acetyl coenzyme A on the
Pyruvate Carboxylase enzyme.
would
it
be
1- Why
disadvantageous
to
the
organism to have Glycolysis
and
Gluconeogenesis
operating
simultaneously
within
a
cell?
Briefly
describe one example of
reciprocal
regulation
of
Glycolysis
and
Gluconeogenesis, involving
an allosteric regulator. For
the example chosen, write
out the reaction catalyzed
by the enzyme in each
pathway, and indicate the
nature of the effect of the
regulator (e.g., inhibition or
activation).
I- Short Questions:
1- Give the cellular location of the
gluconeogenesis pathway.
2- Enumerate the sources for
gluconeogenesis ?
3. Define futile cycle, relate it to
gluconeogenesis?
4- What are the irreversible reactions
unique to gluconeogenesis?
5- How many ATP are consumed for
synthesis of one molecule glucose
from 2 pyruvates
87
Faculty of Medicine
Biochemical Basis of Medicine I
II- MCQ:
1- Gluconeogenesis is
A. The formation of glycogen
B.The formation of starches
C.The formation of glucose from
noncarbohydrates
D.The formation of glucose from other
carbohydrates
2- Gluconeogenesis uses the same
enzymatic reaction of glycolysis
except for
A. Pyruvate kinase
B.4 irreversible reactions in glycolysis
C.3 irreversible reactions in glycolysis
D.2 irreversible reactions in glycolysis
3- Any compound that can be
converted
to
_____can
be
a
precursor for gluconeogenesis.
A. Citrate
B.Pyruvate
C.Oxaloacetate
D.b and c
III- True / False
1- Glucagon
increases
the
transcription of the gene for
PEP
carboxykinase
in
gluconeogenesis, while insulin
decreases it.
2- Fructose 2,6-bisphosphate is a
modulator that can stimulate
either
glycolysis
or
gluconeogenesis, depending on
cellular glucose concentrations.
3- At high glucagon concentrations
gluconeogenesis will be favored
over glycolysis.
4- The brain normally uses both
glucose and fatty acids as
energy sources.
5- Glycerol is one of the precursor
for gluconeogenesis.
88
Faculty of Medicine
Biochemical Basis of Medicine I
LECTURE # (21 - 22) :
Glycogen Metabolism
DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this lecture you
will be able to:
1-Define
Glycogenesis
and
Glycogenolysis , form a
working definition knowing the
substrates and products involved
and any other key intermediates
produced.
2- Trace tissue location of
Glycogenesis
and
Glycogenolysis,
particularly
tissues or cells in the body
where the pathway is most
important.
3- Locate the cell site of Glycogen
metabolism, where in the cell it
occurs (cytosol).
4- Describe the sequence of
events, the overall reaction
sequence and the number of
stages and reactions:
a. Material Flow:: Trace
the fate of labeled
carbon
or
other
89
Student Notes:
.
Faculty of Medicine
Biochemical Basis of Medicine I
elements through the
pathway
b. Energy flow: Trace
the production and
consumption of ATP
c. Electron flow: trace the
production
and
consumption
of
reducing power.
5- Identify the Key steps, either
those which form major control
sites or those which are main "
branch points"
6- Describe connections to other
pathways and the reciprocal
regulation of both glycogenesis
and glycogenolysis
• Overview of Glycogen metabolism
• Structure and function of Glycogen
• Synthesis of
Glycogen(Glycogenesis)
• Degradation of Glycogen
(Glycogenolysis)
• Regulation of glycogenesis and
Glycogenolysis.
• Glycogen storage diseases
Excess dietary glucose is stored as
glycogen. Glucose can be rapidly and
easily mobilized from glycogen, when the
need arises; for example, between meals
or during exercise. A constant supply of
glucose is essential for life because it is
the main fuel of the brain and the only
90
Faculty of Medicine
Biochemical Basis of Medicine I
energy source that can be used by cells
lacking mitochondria and by contracting
skeletal
muscle(during
anaerobic
glycolysis). Glycogen is therefore an
excellent short – term storage material
that can provide energy immediately.
1.
Required Texts And Resources:
Lippincott Illustrated Reviews, 3rd
edition, Champe & Harvey P: 123 - 134
2. Supplementary Texts And Resources:
Medical Biochemistry, Baynes and
Dominiczek, 1st edition, Mosby
•
•
•
You have the opportunity to watch the CDROM about Glycogen metabolism. You
can access the CD-ROM during your
spare time.
1- Glycogen metabolism
http://web.indstate.edu/thcme/mwking/glycogen.html
2-Glycogen metabolism
http://www.med.unibs.it/~marchesi/glycogen.html
3- Glycogen metabolism book
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer.
chapter.2911
4- Glycogen metabolism animation
http://www.wiley.com/college/fob/quiz/quiz15/1520.html
1- Describe the regulation of the
muscle Glycogen
Phosphorylase enzyme by
local allosteric regulators.
91
Faculty of Medicine
Biochemical Basis of Medicine I
What is the effect of
phosphorylation of the enzyme
via Phosphorylase Kinase? A
diagram may be helpful. What
is the significance of the
allosteric regulation with
regard to cellular metabolism?
2.
a. Diagram and describe the
reaction cascade by which cyclic
AMP alters activity of the
Glycogen Phosphorylase enzyme.
(The process by which cyclic AMP
production is activated by
glucagon or epinephrine may be
omitted here.) Include the
effects of covalent modification
on sensitivity of Glycogen
Phosphorylase to allosteric
regulators. What is the
significance of such a regulatory
cascade in liver in relation to the
well being of the whole
organism?
b. How does the rise in cytosolic
[Ca++] that occurs during
activation of muscle contraction
affect glycogen breakdown? How
is this significant with regard to
metabolism during muscle
contraction?
1- Explain how genetic deficiency
of each of the following enzymes
leads to intracellular glycogen
accumulation (glycogen storage
disease) along with the specific
symptoms listed:
•
Deficiency of Glucose-6-phosphatase in
liver, causing glycogen accumulation
plus hypoglycemia (low blood glucose)
92
Faculty of Medicine
•
•
Biochemical Basis of Medicine I
when fasting.
Deficiency of Glycogen Phosphorylase
in muscle, causing glycogen
accumulation plus muscle cramps with
exercise.
Deficiency of Phosphofructokinase in
muscle, causing glycogen accumulation
plus inability to exercise.
I- Short Questions:
1- Give the cellular location of
Glycogen metabolism.
2- What are the main stores of
Glycogen in body ?
3. Enumerate the enzymes of
Glycogenesis and Glycogenolysis.
4- What is the advantage of branched
structure of glycogen.
5–
What is the difference between
glycogenolysis in liver and
muscles?
6- Enumerate Glycogen storage
diseases.
II- MCQ:
1- The enzyme which the key
regulatory step in glycogen
biosynthesis is
A. Glycogen synthase
B. Glycogenin
C. Branching enzyme
D. Phosphoglucomutase
2- Protein kinase A, which
stimulates glycogen
degradation, is activated
directly by
A. Glucagon
93
Faculty of Medicine
Biochemical Basis of Medicine I
B. Insulin
C. Epinephrine
D. Cyclic AMP
3- Glucose 1-phosphate formed by
glycogenolysis is converted to
glucose 6-phosphate by
phosphoglucomutase because
A. Glucose 6-phosphate is more stable
B. Glucose 6-phosphate is converted to
free glucose
C. Glucose 6-phosphate is an intermediate
in several pathways, including
glycolysis
D. Glucose 6-phosphate can be
transported to the liver
III- True / False
1- Enzymes to regulate glycogen
metabolism are always active
when phosphorylated by protein
kineses.
2- Since caffeine inhibits cAMP
phosphodiesterase,
too
much
coffee can result in synthesis of too
much glycogen.
3-UDP-glucose is a precursor of
glycogen in all cells.
5-
Glycogen
storage
disease
results
in
glycogen
accumulation in liver and
kidneys. It can be controlled
by changing ones diet.
94
Faculty of Medicine
Biochemical Basis of Medicine I
LECTURE # (23) :
Pentose phosphate pathway
DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this lecture you will be
able to:
1. Define the pentose phosphate
pathwaw , form a working
definition knowing the substrates
and products involved and any
other key intermediates produced.
2- Trace tissue location of pentose
phosphate pathwaw, particularly
tissues or cells in the body where
the pathway is most important.
3- Locate the cell site of glycolysis,
where in the cell it occurs
(cytosol).
4- Describe the sequence of events,
the overall reaction sequence and
the number of stages and
reactions:
a. Material Flow:: Trace
fate of labeled carbon
other elements through
pathway
b. Energy flow: Trace
95
the
or
the
the
Student Notes:
.
Faculty of Medicine
Biochemical Basis of Medicine I
production and consumption
of ATP
c. Electron flow: trace the
production and consumption
of reducing power
5- Identify the Key steps, either
those which form major control
sites or those which are main "
branch points"
6- Describe connections to other
pathways, with the emphasis on
the role of NADPH in other
biochemical pathways
• Overview of pentose phosphate
pathwaw
• Irreversible oxidative reactions
• Reversible nonoxidative reactions
• Uses of NADPH
• Glucose 6 – phosphate
Dehydrogenase Deficiency
The pentose phosphate pathway occurs in
the cytosol of the cell. The pathway
provides a major portion of body's
NADPH, which functions as a biochemical
reductant. It also produces ribose 5phosphate required for the biosynthesis of
nucleotides.
96
Faculty of Medicine
Biochemical Basis of Medicine I
1.
Required Texts And Resources:
Lippincott Illustrated Reviews, 3rd
edition, Champe & Harvey P: 143- 154
2. Supplementary Texts And Resources:
Medical Biochemistry, Baynes and
Dominiczek, 1st edition, Mosby
•
•
•
You have the opportunity to watch the CDROM about pentose phosphate pathway.
You can access the CD-ROM during your
spare time.
1- Pentose phosphate pathway
http://web.indstate.edu/thcme/mwking/pentosephosphate-pathway.html
2- Pentose phosphate pathway
http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/m
b2/part1/pentose.htm
3- Pentose phosphate pathway (PowerPoint)
presentation
www.cwu.edu/~geed/543/Pentose%20Phosphate%20Pat
hway.ppt
4- Pentose phosphate pathway (poweeroint )
www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb2/part1/15pentose.ppt
1- Diagram and describe the
mechanism of the reaction
catalyzed by the enzyme
Transaldolase, including
structures of major
intermediates.
2. Write out the linear (oxidative)
portion of the Pentose Phosphate
Pathway, giving names and
structures of substrates and
97
Faculty of Medicine
Biochemical Basis of Medicine I
reactants, and the name of each
enzyme. Summarize in words
what happens at each step. What
two products of the linear
portion of the Pentose Phosphate
Pathway have essential roles in
anabolic metabolism? What are
these roles?
Clinical Question
1- In male patients who are
homozygous for glucose 6phosphate dehydrogenase
(G6PD) deficiency,
pathophysiologic consequence
are more apparent in
erythrocytes (RBCs) than in
other cells, such as in the liver.
EXPLAIN.
I- Short Questions:
1- Give the cellular location of the
pentose phosphate pathway
2- What are the main products of
pentose phosphate pathway ?
3. Enumerate sources of NADPH?
4- What are the uses of NADPH in our
body. Enumerate? .
5-
What are the effects of glucose 6phosphate dehydrogenase
deficiency
98
Faculty of Medicine
Biochemical Basis of Medicine I
II- MCQ:
1- The major regulatory step of the
pentose phosphate pathway is
catalyzed by which enzyme?
A. transaldolase
B. phosphofructokinase-1
C. glucose 6-phosphate dehydrogenase
D. ribose 5-phosphate isomerase
2- The non-oxidative stage of the
pentose phosphate pathway
produces substances that are
intermediates of ___________.
A. glycolysis
B. the citric acid cycle
C. the Cori cycle
D. glycogenolysis
3- Which is not a function of the
main products of the pentose
phosphate pathway?
A. To maintain the reduced form of iron in
hemoglobin.
B.To provide reducing power for the
synthesis of fatty acids.
C. To serve as precursors in the
biosynthesis of RNA and DNA.
D. To raise the concentration of cAMP.
III- True / False
1- Glucose 1,6-bisphosphate is
the primary starting substrate
for the pentose phosphate
pathway.
2- Two molecules of NADPH are
generated for each molecule of
glucose 6-phosphate that
enters the pentose phosphate
pathway.
99
Faculty of Medicine
Biochemical Basis of Medicine I
3- Rapidly dividing cells generally
have a high pentose phosphate
pathway activity.
4- The enzyme transketolase
transfers 2-carbon units from
ketose phosphates to aldose
phosphates
5- NADH and pentose are the
main products of pentose
phosphate pathway
100
Faculty of Medicine
Biochemical Basis of Medicine I
LECTURE # (24):
Metabolism of Monosaccharides and
Disaccharides
DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this lecture you will
be able to:
1- Define
pathways for fructose,
Galactose and Lactose Metabolism ,
form a working definition knowing
the substrates and products involved
and any other key intermediates
produced.
2- Trace tissue location of these
pathways, particularly tissues or
cells in the body where the pathway
is most important.
3- Locate the cell site of these
pathways, where in the cell it occurs
(cytosol).
4- Describe the sequence of events,
the overall reaction sequence and
the number of stages and reactions:
a.
Material Flow:: Trace
the fate of labeled carbon or other
elements through the pathway
b.
Energy flow: Trace
the production and consumption of
101
Student Notes:
.
Faculty of Medicine
Biochemical Basis of Medicine I
ATP
c.
Electron flow: trace the
production and consumption of
reducing powerIdentify the Key
steps, either those which form major
control sites or those which are main
" branch points"
5- Describe connections to other
pathways especially Glycolysis
•
•
•
•
Overview
Fructose metabolism
Galactose metabolism
Lactose synthesis
Although many monosaccharides have
been identified in nature, only a few
sugars appear as metabolic intermediates
or as structural components in mammals.
The major source of fructose is sucrose,
while the major dietary source of
galactose is lactose, entry of both to cells
is insulin - independent both can be
metabolized for energy generation through
glycolysis.
1.
Required Texts And Resources:
Lippincott Illustrated Reviews, 3rd
edition, Champe & Harvey P: 135 – 142
2. Supplementary Texts And Resources:
Medical Biochemistry, Baynes and
Dominiczek, 1st edition, Mosby
102
Faculty of Medicine
Biochemical Basis of Medicine I
•
•
•
You have the opportunity to watch the CDROM about Monosaccharide metabolism.
You can access the CD-ROM during your
spare time.
1- Fructose Metabolism
http://www.gpnotebook.co.uk/cache/1798635578
m
2-Fructosa Web site
http://www.drkaslow.com/html/fructose.html
3- Fructose and Galactose Metabolism
http://web.indstate.edu/thcme/mwking/non-gluc
sugar-metabolism.html
4- Galactose Metabolism
http://www.gpnotebook.co.uk/cache/1899298874.htm
Describe, how different monosaccharides
can be interconverted, Explain the
benefits of this interconversion to body
metabolism.
1- Clinical Question
A newborn baby experienced
abdominal distension, severe
bowel cramps, and diarrhea
after being fed milk. A
hydrogen analysis of his
exhaled breath discovered an
eighty – fold increase in the
production of H2 ninety
minutes after milk feeding.
a- Explain the case
103
Faculty of Medicine
Biochemical Basis of Medicine I
b- This condition is
preventable or not?
2- Clinical Case
A galactosemic female is able
to produce lactose, How?
I- Short Questions:
1- What is the main source of dietary
fructose?.
2- What is the main source of dietary
galactose?.
3. Although fructose is more sweaty
than Glucose it is not
recommended to be an exchange
to it in our diet
4- What is the effects Galactokinase
deficiency.
5- Define fructosuria, what is its
cause.
II- MCQ:
1- 1- Which is an intermediate
formed in the conversion of glucose
to fructose?
A. glucose-1-phosphate
B. sorbitol
C. ribose
D. aldose reductase
2- What types of reactions are
involved in the two-step conversion
of glucose to fructose?
A. reduction followed by oxidation
B. two sequential hydrolysis reactions
C. hydrolysis followed by isomerization
D. phosphorylation followed by
104
Faculty of Medicine
Biochemical Basis of Medicine I
dephosphorylation
3- What is a cause of cataracts in
the eye lens of individuals with
diabetes?
A.Accumulation of sorbitol and protein
precipitation in the lens.
B. Precipitation of glucose not oxidized
by glycolysis in the lens.
C. The absence of membrane transport
proteins for pyruvate in the lens cells.
D. Lack of regulation of gluconeogenesis
in the lens and the accumulation of
fructose.
IV- True / False
1- Lactose is the main source
of dietary fructose.
2- Absorption of fructose is insulin
dependent.
3- Aldose reductase reduces
glucose, producing sorbitol
4- Classic galactosemia results from
missing of Galactose kinase
5- Lactose is synthesized by lactase
synthase from UDP glucose and
Galactose.
105
Faculty of Medicine
Biochemical Basis of Medicine I
LECTURE # (25) :
Fatty acid oxidation
DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this lecture you will be able
to:
1- Sequence the reactions catalyzed by acylCoA synthetase, carnitine palmitoyl
transferaseI,carnitine-acylcarnitine
translocase, and carnitine palmitoyl
transferaseII.
2Indicate which of these enzymes is
regulated by malonyl-CoA.
3- Explain the importance of carnitine for the
oxidation of long-chain fatty acid but not
short- and medium-chain fatty acids.
4-
Discuss the steps of beta oxidation of
fatty acids.
5- Explain the importance of citric acid cycle
for the oxidation of fatty acids .
6-
Calculate the yield of ATP that is formed
through the complete oxidation of one
mole of palmitic acid.
7- Indicate the roles of long chain-, medium
chain- and short chain-acyl CoA
dehydrogenases in the oxidation of
long chain fatty acids. Explain why a
defect in the medium chain enzyme
results in excretion of dicarboxylic acids
and acyl carnitine esters in the urine.
106
Student Notes:
.
Faculty of Medicine
Biochemical Basis of Medicine I
• Tissues that are most active in
oxidation of fatty acids and its sub
cellular location
• Conditions which favor the process
of oxidation of fatty acids
• Role of carnitine in the process of
beta oxidation
• The difference in oxidation of long,
medium and short chain fatty acids
• The steps of beta oxidation
• Energy gained of beta oxidation
• Regulation of beta oxidation
• The other types of fatty acid
oxidation
• Diseases associated with genetic
abnormality of fatty acid oxidation
Beta oxidation takes place in fed state in certain
tissues as a source of energy, in starvation it is
stimulated to provide energy for many tissues as
liver (which becomes completely dependent on it
as a source of energy.
1.
Required Texts And Resources:
Lippincott Illustrated Reviews, 3rd
edition, Champe & Harvey. (187-193)
2. Supplementary Texts And Resources:
Medical Biochemistry, Baynes and
Dominiczek, 1st edition, Mosby. (pp 169173)
•
•
•
You have the opportunity to watch the CDROM about fatty acid oxidation. You can
access the CD-ROM during your spare
time.
107
Faculty of Medicine
Biochemical Basis of Medicine I
1http://www.dentistry.leeds.ac.uk/biochem/t
hcme/fatty-acid-oxidation.html
2-
http://www.biocarta.com/pathfiles/betaoxi
dationPathway.asp
3-
http://ull.chemistry.uakron.edu/Pathways/
b_oxidation/index.html
4-
http://www.biocarta.com/pathfiles/boxnpP
athway.asp
5http://www.biocarta.com/pathfiles/h_cptPathway.asp
6http://www.brookscole.com/chemistry_d/temp
lates/student_resources/shared_resources/an
imations/carnitine/carnitine1.html
7-
http://www.biocarta.com/pathfiles/oddnum
berchainPathway.asp
8http://www.biocarta.com/pathfiles/polyunsatfa
ttyacidPathway.asp
1- Try to explain the sequence of
events that takes place in the
mitochondria during beta oxidation
of fatty acid
2- Write down how beta oxidation is
regulated
1-
Clinical Question: In diabetic
patient type I, do you expect that
beta oxidation of fatty acid to be
increased, decreased or normal
and why?
2Clinical Case: A three month
old baby brought to you by his
mother, she was complaining that
the baby seemed to be lethargic
and does not grow well, and he
108
Faculty of Medicine
Biochemical Basis of Medicine I
was on breast fed only. What
possible reason(s) may be the
cause of this condition?
I- Short Questions:
a) Name the different types of oxidation of
fatty acid
b) List the difference between fatty acid
synthesis and beta oxidation regarding
hydrogen carrier used and the site they
occur
II- MCQ:
1- Two high energy bonds are lost during
β oxidation of long chain fatty acids in:
a)
Transport of acyl carnitine inside
the mitochondria
b)
Formation of acyl CoA inside the
mitochondria
c)
Formation of acyl CoA in the
cytoplasm
d)
Release of acetyl CoA from acyl
CoA by the action of thiolase
enzyme
e) Non of the above
2- All the following are intermediate in βoxidation except:
a)
FADH
b)
NADPH
c)
NADH
d)
Acetyl CoA
e)
All of the above
III- True / False
a- The major type of fatty acid
oxidation in most of he tissues is
omega oxidation
b- Beta oxidation takes place in all
tissues
c- Compared to carbohydrate oxidation
of fatty acids generate smaller
quantity of ATP
109
Faculty of Medicine
Biochemical Basis of Medicine I
LECTURE # (26) :
Fatty acid synthesis
DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this lecture you will be
able to:
1-
Identify the substrate for the building of fatty
acid and where it is made. Explain how this
substrate is transferred to the cytoplasm.
2- Describe the importance of glycolysis in the
cytosol for fatty acid synthesis.
3- Discuss how the fatty acid synthase enzyme
complex works.
4- Explain how stearic acid and oleic acid are
synthesized from palmitic acid and in what
regions of the cell they are synthesized.
5- Describe the different mechanisms of shortterm control of the formation of fatty acids.
6- Indicate the roles of insulin and glucagon in the
regulation.
9- Describe long-term control (enzyme induction)
of the formation of fat. Indicate the enzymes that
are subject to long term control.
10-Explain what prevents the liver from oxidizing
fatty acids at the same time it is synthesizing fatty
acids.
• Tissue and subcellular location for
fatty acid synthesis
• Transport of the building block for
110
Student Notes:
.
Faculty of Medicine
•
•
•
•
•
Biochemical Basis of Medicine I
fatty acid synthesis from the
mitochondria to the cytoplasm
The generation of the substrates for
fatty acid synthesis in the cytoplasm
The arrangement and structure of
fatty acid synthesase enzyme
Energy requirement for fatty acid
synthesis
Regulation of fatty acid synthesis
Elongation and unsaturation of fatty
acid
Fatty acid synthesis is an anabolic process, so it
is favored during the fed state and inhibited
during starvation through hormonal regulation
which also activates fatty acid oxidation, so
during starvation fatty acid synthesis is shut down
and oxidation is turned on. Acetyl CoA is the
substrate for fatty acid synthesis which is
produced in the mitochondria and has to be
transported to the cytoplasm in the form of citrate.
In the cytoplasm the other requirement for fatty
acid synthesis are present (NADPH and fatty acid
synthesase complex)
1.
Required Texts And Resources:
Lippincott Illustrated Reviews, 3rd
edition, Champe & Harvey. (pp 179186)
2. Supplementary Texts And Resources:
Medical Biochemistry, Baynes and
Dominiczek, 1st edition, Mosby. (pp 179184)
•
•
•
You have the opportunity to watch the CDROM about fatty acid synthesis You can
access the CD-ROM during your spare
time.
111
Faculty of Medicine
Biochemical Basis of Medicine I
1- http://ull.chemistry.uakron.edu/Path
ways/FA_synthesis/index.html#
2http://www.genome.ad.jp/kegg/pathway
/map/map00561.html
3http://ull.chemistry.uakron.edu/Pathways/FA_
synthesis/index.html
4http://ull.chemistry.uakron.edu/genobc/
Chapter_24/
5http://www.uic.edu/depts/mcam/mcbc/l
ect_2004/lecture_27.pdf
1- Outline and contrast the processes
of fatty acid synthesis and oxidation
2- Write down the source(s) of each of
the substrate for fatty acid synthesis
1Clinical Case
Obesity, which will be covered
in the tutorial.
I- Short Questions:
a) Name the key regulatory
enzyme in fatty acid
synthesis
b) Using a diagram drew how
this enzyme is controled
112
Faculty of Medicine
Biochemical Basis of Medicine I
II- MCQ:
1- Acetyl groups for fatty acid synthesis is
derived mainly from:
a)
b)
Only glucose
Ketogenic amino acids
only
c)
Beta oxidation of fatty acid
d)
Glucose and amino acids
e) Non of the above
2- Acetyl CoA for fatty acid synthesis is
produced in the cytoplasm by the
action of:
a)
Acetyl CoA synthetase
b)
Citrate lyase
c)
Pyruvate dehydrogenase
d)
Thiolase
e)
Non of the above
II- True / False
a) The synthesis of fatty acids
occurs in the cytoplasm of the
cells
b) The key regulatory enzyme in
fatty acid synthesis is the fatty
acid synthesase
c) Insulin hormone inhibits fatty
acid synthesis
d) Citrate lyase enzyme has no role
in the process of fatty acid
synthesis
113
Faculty of Medicine
Biochemical Basis of Medicine I
LECTURE # (27,28)
Lipogenesis
DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this lecture you will be
able to:
1. Define lipogenesis and its
importance
2. Locate the important sites
(tissues) for lipogenesis and its
intracellular location
3. Discuss the favorable conditions
for lipogenesis
4. Differentiate between lipogenesis
in adipose tissues and other tissues
and explain this differences
5. Trace the substrate of lipogenesis
to its final product
• Overview and definition of
lipogenesis
• Sites of lipogenesis (tissues and
subcellular level)
• Substrates for lipogenesis
• Energy utilization of lipogenesis
• Regulation of lipogenesis
• Fed and fasting conditions and their
effect on lipogenesis
114
:
Student Notes:
.
Faculty of Medicine
Biochemical Basis of Medicine I
How excess calorie are stored in the form of
triglycerides and how this process utilizes
excess CHO and protein for its synthesis to be
utilized during fasting and starvation
conditions.
1.
Required Texts And Resources:
Lippincott Illustrated Reviews, 3rd
edition, Champe & Harvey. (pp 185187)
2. Supplementary Texts And Resources:
Medical Biochemistry, Baynes and
Dominiczek, 1st edition, Mosby. (pp 185187)
•
•
•
You have the opportunity to watch the CDROM about lipogenesis. You can access
the CD-ROM during your spare time.
1- http://www.lipidsonline.org/
2- http://ull.chemistry.uakron.edu/Pa
thways/FA_synthesis/index.html#
3- http://www.genome.ad.jp/kegg/pa
thway/map/map00561.html
4- http://www.biochem.arizona.edu/c
lasses/bioc801/power/lec27.ppt#2
56,1,Slide 1
5- http://www.genome.jp/kegg/pathw
ay/map/map01130.html
6- http://www.biocarta.com/pathfiles
/h_vobesityPathway.asp
115
Faculty of Medicine
Biochemical Basis of Medicine I
1. Explain why the liver is able to utilize free
glycerol for the synthesis of triglyceride
glycerol, but the adipose tissue must have
glucose in order to synthesize glycerol
3-phosphate. Give the reaction catalyzed by
the enzyme missing in the adipose cell.
2. Write down the role of insulin in
lipogenesis
Clinical Question:
1. What is BMI and how it is used
for classification of obesity?
Clinical Case:
2. Obesity, which will be covered
in the tutorial.
I- Short Questions:
1- State the tissues and the subcellular
location of lipogenesis
2- Outline the major difference (s) between
lipogenesis in the liver and that in the
adipose tissue
III-
MCQ:
1- In liver lipogenesis, glycerol 3phosphate can be obtained by:
a)The action of glycerol
kinase enzyme only
b) Through glycolysis
intermediates only
c)Both of the above
d)Non of the above
116
Faculty of Medicine
Biochemical Basis of Medicine I
2- Adipocytes contain fat droplets which
serve to provide to an animal
a)Increased cell volume
b) Insulation
c) provide energy
d) a and b
e) b and c
III- True / False
a. Lipogenesis takes place in
the cytoplasm of the adipose
tissues and the liver
b. Glycerol kinase is very
active enzyme in lipogenesis
in the adipose tissue
c. Lipogenesis is stimulated by
insulin and inhibited by
glucagons
117
Faculty of Medicine
Biochemical Basis of Medicine I
LECTURE # (29) :
Ketone bodies metabolism
Student Notes:
.
DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this lecture you will be able
to:
1- Define what is meant by ketogenesis
and ketolysis
2- Enumerate the different ketone bodies
3- Evaluate the process of synthesis of
ketone bodies
4- Explain the
ketogenesis
role
of
the
liver
in
5- Explain why ketone bodies synthesis is
activated during fasting and starvation
• Definition of ketogenesis and
ketolysis
• The central role of the liver in
ketogenesis and its inability to
utilize them
• The steps of ketogenesis in the liver
• The steps of ketolysis in extra
hepatic tissues
• Regulation of ketogenesis and
ketolysis
•
•
•
118
Faculty of Medicine
Biochemical Basis of Medicine I
Remember that ketone bodies are used as a
major source of energy during starvation in
most of the tissues even the brain to decrease
the process of gluconeogenesis from muscle
protein and spare the glucose produced from
gluconeogenesis mainly to the brain and for
the tissues which do not have mitochondria
such as RBCs.
1.
Required Texts And Resources:
Lippincott Illustrated Reviews, 3rd
edition, Champe & Harvey. (pp 193197)
2. Supplementary Texts And Resources:
Medical Biochemistry, Baynes and
Dominiczek, 1st edition, Mosby. (pp 173176)
•
•
•
You have the opportunity to watch the CDROM about fatty acid oxidation. You can
access the CD-ROM during your spare
time.
1- http://www.biocarta.com/pathfiles/ke
tonebodiesPathway.asp
2- http://ull.chemistry.uakron.edu/genobc/Chapter
_24/
3- http://ull.chemistry.uakron.edu/Pathway
s/ketone_bodies/index.html
1- Draw the steps of ketogenesis
indicating the steps during which
119
Faculty of Medicine
Biochemical Basis of Medicine I
CoA-SH is regenerated
2- Drew a graph connecting both beta
oxidation and ketogenesis
1-
Clinical Question:
a) In type I diabetes, ketone
bodies tend to increase more than
type II, explain why?
2-
Clinical Case: A type I diabetic
patient delivered to you in a coma
in the ER , his blood glucose level
was 500 mg/dl (27.8 mmol/L), his
breath had the acetone
charachtristic odour.
a) What other investigation(s)
would you like to do?
b) What type of coma is it?
c) What is the biochemical bases
of this coma?
I- Short Questions:
1- Explain why ketogenesis is essential for
energy production in the liver during
starvation
2- Explain why the liver can not utilize ketone
bodies
II- MCQ:
1- Regarding ketogenesis and ketolysis:
a) Ketogenesis takes place in
the mitochondria of
extrahepatic tissues while
ketolysis in the cytoplasm
of extrahepatic tissues
b) Ketolysis takes place in
the cytoplasm of
extrahepatic tissues
c) Ketogenesis and ketolysis
takes place in liver
mitochondria
d) Ketogenesis takes place in
liver mitochondria only
120
Faculty of Medicine
Biochemical Basis of Medicine I
e) All of the above
2- Regeneration of CoA-SH takes place
during ketogenesis in the step (s) of:
a)
formation of acetoacetyl
CoA
b)
formation of beta
hydroxybutyrate from
acetoacetate
c)
formation of
hydroxymethylglutaeyl
(HMG) CoA
d)
Both (a) and (c)
e)
All of the above
III- True / False
1- Ketogenesis takes place in all the
tissues
2- Ketone body oxidation is the major
source of energy for most of the
tissues in the absorptive state
3- Ketogenesis takes place in the
cytoplasm of the liver only
121
Faculty of Medicine
Biochemical Basis of Medicine I
LECTURE # (30)
Lipolysis
DEPARTMENT: Clinical Biochemistry
TUTOR:
TEACHING LOCATION: Auditorium
By the end of this lecture you will be able to:
1- Define lipolysis
2- Locate the site where it happens in he tissue
and the subcellular location
3- Explain the importance of this pathway in
case of fasting and most important during
starvation
4- Trace the starting substrate to its final fate
5- Discuss how this pathway is tightly regulated
•
•
•
•
Definition of lipolysis
Conditions favoring lipolysis
Site and subcellular level
The importance of lipolysis for energy
providing
• HSL and its regulation
• The effect of fed, fasting and exercise
conditions on lipolysis
Remember that TG is the major energy store
in your body, the calorie content of TG in
adipose tissue is about 120000, those
calories are mobilized through the process of
lipolysis during starvation to provide energy in
the form of free fatty acid for oxidation in most
122
:
Student Notes:
.
Faculty of Medicine
Biochemical Basis of Medicine I
of the tissues especially the liver and
muscles.
1. Required Texts And Resources: Lippincott
Illustrated Reviews, 3rd edition, Champe &
Harvey. (pp 187-188)
2. Supplementary Texts And Resources:
Medical Biochemistry, Baynes and
Dominiczek, 1st edition, Mosby.
•
•
•
You have the opportunity to watch the CDROM about lipolysis. You can access the
CD-ROM during your spare time.
1- http://www.wiley.com/legacy/college/bo
yer/0470003790/animations/fatty_acid_
metabolism/fatty_acid_metabolism.htm
2- http://www.elmhurst.edu/~chm/vchemb
ook/620fattyacid.html
3- http://www.webpages.uidaho.edu/~dcole/Lipids
%20Lecture%2012.pdf
1- Draw how HSL is hormonally
regulated
1a)
Clinical Question
Can you explain why the
marathon runner is fed during the
marathon in such a ay that his blood
glucose is kept low
2a)
Clinical Case
A patient was delivered to the ER
123
Faculty of Medicine
Biochemical Basis of Medicine I
with history of type I DM and he
was in coma and you diagnosed
him as diabetic keoacidosis coma,
what do you expect about his
plasma level of free fatty acid (low,
normal or high) and why?
I- Short Questions:
1- Define lipolysis and mention where it
happens
IV-MCQ:
1-Regarding lipolysis
a) It is mostly active during fed state
b) It takes place in the adipose tissue
and the released fatty acids are
carried by chlomicrons to
peripheral tissues for oxidation
during fasting condition
c) It is stimulated by insulin
d) The released fatty acids are carried
and transported to peripheral
tissues by plasma albumin
e) All of the above
2-Regarding hormone-sensitive lipase:
a) It is active in the dephosphorylated
form
b) It is activated by the action of the
insulin hormone
c) It is activated through the action of
c-AMP dependent protein kinase
d) Its activity is maximum during the
fed state
e) Non of the above
V- True / False
1- Lipolysis means the
mobilization of energy storage
in adipose tissue in the form of
ketone bodies
124
Faculty of Medicine
Biochemical Basis of Medicine I
2- HSL is the key regulatory
enzyme in lipolysis
3- Glucagon hormone stimulates
the process of lipolysis while it
is inhibited by insulin
125
Faculty of Medicine
Biochemical Basis of Medicine I
PRACTICALS
Practical (1) : Enzymes: Amylase activity in serum
Department: Biochemistry
Teaching location: Classroom
By the end of this practical the student will be able to:
o Determine the optimum temperature for enzyme activity
o Estimate serum amylase activity in the provided sample
o Explain the function of serum amylase
o Discuss the diagnostic importance of serum amylase
•
Determination of serum amylase
•
Explaining the effect of temperature on enzyme activity
•
Discuss the role of measurement of serum amylase in disease condition
•
Evaluating the role of amylase in GIT digestion of nutrients
Transferable skills:
•
Interrelate laboratory data with clinical findings
READING: Laboratory Handouts will be distributed
126
Faculty of Medicine
Biochemical Basis of Medicine I
Practical (2) : Enzymes: Estimation of serum alkaline phosphatase
Department: Biochemistry
Teaching location: Classroom
By the end of this practical the student will be able to:
o Determine serum alkaline phosphatase
o Evaluate the effect of enzyme inhibitors on enzymatic activity
o Define Km and Vmax
o Show how the Lineweaver-Burk plot can be used to evaluate Km and
Vmax
•
Determination of serum alkaline phosphatase
•
The definition of Km and Vmax and the effect of enzyme inhibitors on both of
them
•
Plotting of Lineweaver-Burk plot and its utilization for evaluation of Km and
Vmax
•
Clinical importance of measurement alkaline phosphatase
Transferable skills:
•
Interrelate laboratory data with clinical findings
•
Serum alkaline phosphatase as marker for bone and liver diseases
READING: Laboratory Handouts will be distributed
127
Faculty of Medicine
Biochemical Basis of Medicine I
Practical (3) : Enzymes: Serum CK isoenzymes
Department: Biochemistry
Teaching location: Classroo‫ة‬
By the end of this practical the student will be able to:
o Define what is meant by isoenzymes
o Separate the different CK isoenzymes using electrophoresis
o Evaluate the role of CK in tissues
o Discuss the role and importance of measuring CK isoenzymes in different
diseases conditions
•
Separation of serum CK isoenzymes
•
Function of Ck in different tissues
•
The different isoenzymes of CK and relation to different diseases
Transferable skills:
•
Interrelate laboratory data with clinical findings
•
How to use CK isoenzymes in evaluating cardiac and muscle
diseases
READING: Laboratory Handouts will be distributed
128
Faculty of Medicine
Biochemical Basis of Medicine I
Practical (4): Biologic Oxidation. Oxidative phosphorylation and effect of uncouplers
Department: Biochemistry
Teaching location: Classroom
By the end of this practical the you will be able to:
o Determine the amount of inorganic phosphate consumed in the process of oxidative
phosphrylation
o Explain the effect of uncouplers on this phosphrylation
o
Discuss how glycolysis was inhibited in this reaction
•
Determination of activity of the process of oxidative phosphrylation
•
Explaining the effect of uncouplers
•
Differentiation between the mechanism of action of different types of uncouplers
Transferable skills:
•
Interrelate laboratory result with some drugs used as uncouplers
READING: Laboratory Handouts will be distributed
129
Faculty of Medicine
Biochemical Basis of Medicine I
Practical (5) : Serum lactate
Department: Biochemistry
Teaching location: Classroom
By the end of this practical the student will be able to:
o Determine blood lactate
o Evaluate the importance of determination of serum lactate
o To discuss how one enzyme affects different metabolic pathways
•
Determination of serum lactate
•
The importance of measurement blood lactate in evaluating children with hypoglycemia
•
The relation of lactic acidosis to enzyme deficiency such as glucose 6-phosphatase
deficiency
Transferable skills:
•
Interrelate laboratory data with clinical findings
READING: Laboratory Handouts will be distributed
130
Faculty of Medicine
Biochemical Basis of Medicine I
Practical (6) : Serum lactate dehydrogenase isoenzymes
Department: Biochemistry
Teaching location: Classroom
By the end of this practical the student will be able to:
o Use electrophoresis for separation of LDH isoenzymes
o Differentiate between the different LDH isoenzymes (sources and function)
o Evaluate the role of LDH isoenzyme in disease diagnosis
•
Determination of serum LDH isoenzymes using cellulose electrophoresis
•
The role of LDH in different metabolic pathways
•
The sources of LDH isoenzymes and its role in diagnosis
Transferable skills:
•
Interrelate laboratory data with clinical findings
•
How to use LDH isoenzymes in evaluating cardiac cases
READING: Laboratory Handouts will be distributed
131
Faculty of Medicine
Biochemical Basis of Medicine I
Practical (7) : OSPE TRAINING
Department: Biochemistry
Teaching location: Classroom
By the end of this practical the student will be able to:
o Be familiar with the OSPE
•
8-9 stations will be included, two of them will be related to the previously
mentioned tests (determination of the analytes), the other will include questions
to evaluate the student benefits of the information given in these practicals.
Transferable skills:
•
Accuracy of performing the test
•
Utilization of data in the different stations for interpretation of clinical
cases
READING: Laboratory Handouts will be distributed
132
Faculty of Medicine
Biochemical Basis of Medicine I
Practical (8) : Liver glucose-6-phosphatase deficiency
Department: Biochemistry
Teaching location: Classroom
By the end of this practical the student will be able to:
o Determine glucose-6-phosphatase in tissue extract
o Discussing the different changes in blood glucose, lactate, pyruvate, fatty acids,
ketone bodies and uric acid found in this case
o Explaining the basis of other glycogen storage diseases
•
Determination of glucose-6-phosphatase activity in liver tissues
Transferable skills:
•
Interrelate laboratory data with clinical findings
•
Correlation of lactic acidosis with glucose-6-phosphatase deficiency
READING: Laboratory Handouts will be distributed
133
Faculty of Medicine
Biochemical Basis of Medicine I
Practical (9) : Plasma glucose estimation
Department: Biochemistry
Teaching location: Classroom
By the end of this practical the student will be able to:
o Estimate plasma glucose
o Differentiate between the different methods for measuring plasma glucose
o Utilize the result of plasma glucose to diagnose a case of hyperglycemia
o Discuss how to monitor a diabetic patient
•
Determination of plasma glucose
•
Difference between blood glucose and plasma glucose
•
WHO classification of hyperglycemia
Transferable skills:
•
Interrelate laboratory data with clinical findings
•
How to utilize plasma glucose for diagnosis and monitoring diabetic
patients
READING: Laboratory Handouts will be distributed
134
Faculty of Medicine
Biochemical Basis of Medicine I
Practical (10) : Oral glucose tolerance curve
Department: Biochemistry
Teaching location: Classroom
By the end of this practical the student will be able to:
o Draw glucose tolerance curve
o Utilize this curve in diagnosis of hyperglycemic case
o Differentiate between the different responses in this test
•
Drawing the curve using different glucose concentration
•
Estimation of the different samples (fasting, 60 minutes, 90 minutes and 120 minutes)
•
The difference between oral glucose and intravenous glucose tolerance curve
•
Monitoring of diabetic patient
Transferable skills:
•
Interrelate laboratory data with clinical findings
•
How to utilize plasma glucose for diagnosis and monitoring diabetic
patients
READING: Laboratory Handouts will be distributed
135
Faculty of Medicine
Biochemical Basis of Medicine I
Practical (11) : Lipid: Estimation of plasma total cholesterol
Department: Biochemistry
Teaching location: Classroom
By the end of this practical the student will be able to:
o Estimate plasma cholesterol using cholesterol oxidase method
o Correlate plasma cholesterol level with cardiac diseases
o Utilize biochemical knowledge in treating this patient
•
Measurement of plasma total cholesterol
•
Different types of hyperlipidemia
•
Classification of hypercholesterolemia according to Adult Treatment Panel III
(ATP III) provided by National Cholesterol Education Program (NCEP)
Transferable skills:
•
Interrelate laboratory data with clinical findings
•
Approach a case of hypercholesterolemia
READING: Laboratory Handouts will be distributed
136
Faculty of Medicine
Biochemical Basis of Medicine I
Practical (12) : Lipid: Estimation of plasma Triacylglycerol
Department: Biochemistry
Teaching location: Classroom
By the end of this practical the student will be able to:
o Estimate plasma triacylglycerol
o Evaluate the role of lipoprotein lipase in lipid metabolism
•
Differentiate between the different types of hyperlipidemia
•
Measurement of plasma triacylglycerol
•
Different types of hyperlipidemia
•
Classification of hyperlipidemia according to Adult Treatment Panel III (ATP III)
provided by National Cholesterol Education Program (NCEP)
•
Transferable skills:
•
Interrelate laboratory data with clinical findings
•
Approach a case of hyperlipidemia
READING: Laboratory Handouts will be distributed
137
Faculty of Medicine
Biochemical Basis of Medicine I
Practical (13) : Lipid: Estimation of fecal fat
Department: Biochemistry
Teaching location: Classroom
By the end of this practical the student will be able to:
•
Estimate fecal fat
•
Discuss lipid absorption and factors affecting absorption
•
Discuss malabsorption as a defective in digestion or absorption
•
Estimation of fecal fat
•
Interference of pancreatic damage with the utilization of dietary fat
•
State of digestion and absorption of other macronutrients in this case
•
Different causes that may be encountered in this case for malabsorption
Transferable skills:
•
How to approach a case of steatorrhoea
READING: Laboratory Handouts will be distributed
138
Faculty of Medicine
Biochemical Basis of Medicine I
Practical (14) : OSPE TRAINING
Department: Biochemistry
Teaching location: Classroom
By the end of this practical the student will be able to:
o Be familiar with the OSPE
•
8-9 stations will be included, two of them will be related to the previously
mentioned tests (determination of the analytes), the other will include questions
to evaluate the student benefits of the information given in these practicals.
Transferable skills:
•
Accuracy of performing the test
•
Utilization of data in the different stations for interpretation of clinical
cases
READING: Laboratory Handouts will be distributed
139
Faculty of Medicine
Biochemical Basis of Medicine I
140
Faculty of Medicine
Biochemical Basis of Medicine I
PBL process
• The clinical scenario
•
Key information
• Explore the problem
• What you know
• What you need to know
• Identify learning issues
• Self/group study
• Share the knowledge
• Solve the problem
• Give feedback & reflect
141
Faculty of Medicine
Introduction
Biochemical Basis of Medicine I
Tutorial # 1
Paget’s Disease of Bone
During this week you will work through the case of a Paget’s Disease of Bone
A 74-year old woman presented with a 6-week history of pain localized to the left buttock.
It did not radiate down the lateral aspect of her thigh and was not aggravated by stooping.
On examination there was full movement of both hip joints and no limitation of forward
flexion or extension or lateral rotation. The left buttock was slightly warmer to touch than
the right. Her blood pressure was 160/75 mmHg and pulse 84/min.
Clinical investigations
Plasma
Urea
Reference Range
5.0 mmol/L
25-7.0
Albumin
39 g/L
27-42
Calcium
2.32 mmol/L
2.15-2.55
Phosphate
1.12 mmol/L
0.60-1.40
955 U/L
90-250
ALP
Radiological examination demonstrated extensive Paget’s disease of the pelvis, sacrum and
left femur
142
Faculty of Medicine
Biochemical Basis of Medicine I
By the end of this tutorial the student will be able to:
1. Interpret biochemical abnormalities in clinical cases
2. Comment on the clinical and biochemical findings
3. Learn the diagnostic value of different isozymes
4. Learn the clinical application of enzymes assay in clinical conditions
1. How would you interpret the biochemical investigations?
2. What is the most probably diagnosis of this case? Why?
3. What is the clinical application of ALP assay in such a clinical situation?
4. What is the diagnostic value of different isozymes?
1- Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition,
Champe & Harvey
2. Supplementary Texts And Resources: Medical Biochemistry, Baynes
and Dominiczek, 1st edition, Mosby
Try to access CD-ROM series about enzymes.
1. http://www.nlm.nih.gov/medlineplus/pagetsdiseaseofbone.html
2. http://www.pagetsdisease.com/info/about/diagnosed.jsp?usertrack.filte
r_applied=true&NovaId=2229644978497118671
3. http://www.mountauburn.caregroup.org/body.cfm?xyzpdqabc=0&id=
6&action=detail&AEProductID=HW_Knowledgebase&AEArticleID=
hw1717&AEArticleType=MedicalTest
143
Faculty of Medicine
Biochemical Basis of Medicine I
Learning issues
At the end of the first session you will be able identify the learning issues which
related to the Paget’s Disease of Bone
Try to summarize these learning issues in the table below. We recommend you to
learn about these issues. This will help you to solve the problem in the next
session.
Learning issues
Notes
…………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
…………
……………………………………………………………
144
Faculty of Medicine
Biochemical Basis of Medicine I
Tutorial # 2
Chest Pains
Introduction
During this week you will work through the case of chest pain
You are in charge of a coronary care unit. The previous day, there were 2 admissions via
the accident and emergency services of patients with suspected MI. both men were in their
late 40's and had suffered intense chest pain. Patient (a), a businessman, had been taken ill
at a local restaurant, while patient (b), a teacher, had just returned home after a strenuous
jogging session. Tow blood samples had been taken from each patient, at ≈ 10hr and 24hr
after the onset of chest pains, for assay of serum CK and LDH.
Clinical investigations
Plasma
Patient (A)
Patient (B)
Reference Range
10hr
24hr
10hr
24hr
Total CK
748
850
735
790
20-150 U/L
CK-MB
82
75
25
23
0-3 U/L
LDH
129
182
106
167
45-90 U/L
145
Faculty of Medicine
Biochemical Basis of Medicine I
By the end of this tutorial the student will be able to:
1. Interpret biochemical abnormalities in clinical cases
2. Comment on the clinical and biochemical findings
3. Learn the diagnostic application of cardiac enzymes in heart patients
4. Learn the use of anticoagulant therapy in MI
1. How would you interpret the changes in cardiac enzymes in both patients?
2. Did the results of biochemical tests assist in making the diagnosis?
3. Would screening the population at large for serum enzymes such as CK and
LDH be of predictive value in identifying people at risk of heart attack?
4. One of the treatments that may be given in this situation is the IV
administration of t-PA. What is the basis of this treatment?
1- Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition,
Champe & Harvey
2. Supplementary Texts And Resources: Medical Biochemistry, Baynes
and Dominiczek, 1st edition, Mosby
Try to access CD-ROM series about Enzymes
1. http://en.wikipedia.org/wiki/Myocardial_infarction
2. http://www.guideline.gov/summary/summary.aspx?doc_id=6534
3. http://www.nlm.nih.gov/medlineplus/ency/article/003079.htm
146
Faculty of Medicine
Biochemical Basis of Medicine I
• Learning issues
At the end of the first session you will be able identify the learning issues which
related to chest pain cases.
Try to summarize these learning issues in the table below. We recommend you to
learn about these issues. This will help you to solve the problem in the next
session.
Learning issues
Notes
…………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
…………
……………………………………………………………
147
Faculty of Medicine
Biochemical Basis of Medicine I
Tutorial # 3
Alcohol-Induced Cirrhosis of The Liver
Introduction
During this week you will work through the case of Alcohol-Induced Cirrhosis of
The Liver
A 75-year old woman was admitted to hospital following the sudden onset of a rightsided hemiparesis. She had a history of epilepsy and was on treatment with phenytoin.
Clinical examination confirmed a right-sided weakness; her blood pressure was normal.
Her speech was slurred and her breath smelt strongly of alcohol.
Clinical investigations
Plasma
Bilirubin
Reference Range
12 μmol/L
<21
ALP
275 U/L
21-92
GGT
402 U/L
6-32
AST
34 U/L
6-35
Ethanol
133 mg/dl
Phenytoin
46 μmol/L
148
40-80
Faculty of Medicine
Biochemical Basis of Medicine I
By the end of this tutorial the student will be able to:
1. Interpret biochemical abnormalities in clinical cases
2. Comment on the clinical and biochemical findings
3. Learn the changes of plasma enzymes activities in liver diseases
1. How would you interpret the biochemical investigations?
2. What is the most probably diagnosis of this case? Why?
3. What is the clinical application of ALP assay in such a clinical situation?
4. What are the change patterns of plasma enzymes in liver diseases?
1- Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition,
Champe & Harvey
2. Supplementary Texts And Resources: Medical Biochemistry, Baynes
and Dominiczek, 1st edition, Mosby
Try to access CD-ROM series about Enzymes
1. http://www.healthsystem.virginia.edu/uvahealth/adult_liver/alcohol
.cfm
2. http://www.umm.edu/liver/alcohol.htm
3. http://www.liverfoundation.org/education/info/alcohol/
4. http://www.clevelandclinicmeded.com/diseasemanagement/gastro/a
ld/ald.htm
149
Faculty of Medicine
Biochemical Basis of Medicine I
• Learning issues
At the end of the first session you will be able identify the learning issues which
related to Alcohol-Induced Cirrhosis of The Liver
Try to summarize these learning issues in the table below. We recommend you to
learn about these issues. This will help you to solve the problem in the next
session.
Learning issues
Notes
…………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
…………
……………………………………………………………
150
Faculty of Medicine
Biochemical Basis of Medicine I
Tutorial # 4
Genetic defect in the Pyruvate Dehydrogenase Complex
Introduction
During this week you will work through the case of a Genetic defect in the
Pyruvate Dehydrogenase Complex
A full-term male infant failed to gain weight, had episodes of vomiting, and showed
metabolic acidosis in the neonatal period. A physical examination at 8 months showed
failure to thrive, hypotonia, small muscle mass, severe head lag, and a persistent acidosis,
pH 7 to 7.2. Blood lactate (9 mmol/L), pyruvate (2.4 mmol/L), and alanine (1.36 mmol/L)
were greatly elevated. Since these symptoms suggested a genetic defect in pyruvate
metabolism, treatment with thiamine, biotin, bicarbonate, protein restriction, and a
ketogenic diet were all tried, but none of the treatment alleviated the lactic acidosis. After
informed consent, oral lipoic acid greatly improved the lactic and pyruvic acidemia.The
patient was doing well 2 years later.
By the end of this tutorial you will be able to:
1. Name the enzyme components of pyruvate dehydrogenase complex and
cofactors needed for it.
2. Explain the high plasma concentrations of pyruvate, lactate and alanine in a
case with defect in pyruvate dehydrogenase complex.
3. Recognize the rationale for attempting therapy with thiamine, biotin,
bicarbonate, and protein restriction.
4. Explain why restriction of dietary carbohydrate may not be useful in
treating a patient with genetic defect in pyruvate dehydrogenase complex.
1. What are the enzyme components of pyruvate dehydrogenase complex?
And what are the cofactors needed for it?
151
Faculty of Medicine
Biochemical Basis of Medicine I
2. Why were the plasma concentrations of pyruvate, lactate, and alanine
abnormally high?
3. What was the rationale for attempting therapy with thiamine, biotin,
bicarbonate, and protein restriction?
4. Restriction of dietary carbohydrate to 40% of the food calories has been
fairly effective in alleviating the symptoms of lactic acidosis in patients in
whom the genetic defect in the pyruvate dehydrogenase complex is
presumably in the E1 subcomplex. In this patient it caused a worsening of the
acidosis. Suggest an explanation.
1- Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition,
Champe & Harvey P: 107 - 114
2. Supplementary Texts And Resources: Medical Biochemistry, Baynes
and Dominiczek, 1st edition, Mosby
Try to access CD-ROM series about carbohydrate metaboliosm.
1. www.valuemd.com/usmle-step-1-forum/21747-high-yield-biochemistry
2. watcut.uwaterloo.ca/webnotes/PDF/MeatbolismNotes.pdf
3. www.answer.com/topic/pyruvate-dehydrogenase-complex-deficiency
4. www.wikipedia/wiki/pyruvate dehdrogenase complex defect
152
Faculty of Medicine
Biochemical Basis of Medicine I
• Learning issues
At the end of the first session you will be able identify the learning issues which
related to the genetic defect in the Pyruvate Dehydrogenase Complex
Try to summarize these learning issues in the table below. We recommend you to
learn about these issues. This will help you to solve the problem in the next
session.
Learning issues
Notes
…………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
…………
……………………………………………………………
153
Faculty of Medicine
Biochemical Basis of Medicine I
Tutorial # 5
Pyruvate carboxylase deficiency (Dysfunction of Krebs’ cycle)
Introduction
During this week you will work through the case of a Pyruvate carboxylase
deficiency (Dysfunction of Krebs’ cycle)
A 3-month-old female seemed normal until she developed seizures. The infant became
progressively worse, showing hypotonia, psychomotor retardation, and poor head control.
She had lactic acidosis and an elevated plasma pyruvate level, both more than seven times
the normal amount. Plasma alanine concentration was high, and an alanine load failed to
induce a normal gluconeogenic response. Pyruvate carboxylase activity was measured
using extracts of cultured skin fibroblasts and was found to be less than 1% the normal
level. Fibroblasts from the patient accumulated five times greater than normal amounts of
lipid.
By the end of this tutorial the student will be able to:
1. State the reaction catalyzed by pyruvate carboxylase enzyme.
2. Name the subcellular site of pyruvate carboxylase.
3. Contrast the major biosynthetic function of krebs’ cycle in brain and its main
catabolic function in other tissues as skeletal muscle and heart.
4. Relate the failure of alanine load to induce gluconeogenesis in patients with
pyruvate carboxylase deficiency.
5. Conclude the benefit of glutamine in stimulation the growth of fibroblasts from
a patient with pyruvate carboxylase deficiency disease.
6. Explain the lipid accumulation in cultured fibroblasts in patients with pyruvate
carboxylase deficiency.
7. Interpret the use of glutamic acid and aspartic acid in therapy of pyruvate
carboxylase deficiency.
1. What reaction is catalyzed by pyruvate carboxylase? Where is the enzyme
located in cells?
156
Faculty of Medicine
Biochemical Basis of Medicine I
2. What is the metabolic function of pyruvate carboxylase?
3. Explain the failure of the alanine load to induce gluconeogenesis in the
patient.
4. Why did lipids accumulate excessively in the patient’s fibroblasts?
5. What treatment would you suggest for a patient with this disease?
1- Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition,
Champe & Harvey
2. Supplementary Texts And Resources: Medical Biochemistry, Baynes
and Dominiczek, 1st edition, Mosby
Try to access CD-ROM series about carbohydrate metaboliosm.
١. www.emedicine.com/Med/topic 1967.htm
2. children.webmd.com/Pyruvate_Carboxylase_deficiency
3. www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?di=226150
4. www.answer.com/topic/pyruvate-carboxylase-deficiency
157
Faculty of Medicine
Biochemical Basis of Medicine I
• Learning issues
At the end of the first session you will be able identify the learning issues which
related to the genetic defect in the Pyruvate carboxylase deficiency Try to
summarize these learning issues in the table below. We recommend you to learn
about these issues. This will help you to solve the problem in the next session.
Learning issues
Notes
…………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
……………………………………………………………
158
Faculty of Medicine
Introduction
Biochemical Basis of Medicine I
Tutorial # 6
Von Gierke’s disease
During this week you will work through the case of a Von Gierke’s disease
The patient was a 12-year-old girl who had a grossly enlarged abdomen. She had a history
of frequent episodes of weakness, sweating, and pallor that were eliminated by eating. Her
development had been somewhat slow. Her physical examination revealed the following:
Blood pressure
110/58 mmHg
Temperature
38 ºC
Weight
22.4 kg (low)
Height
128 cm (low)
Lungs
clear
Heart
normal
Abdomen
prominent with slight venous distention
Liver
masssively enlarged, firm and smooth
Spleen & Kidneys
not palpable
The following are laboratory findings for a fasting blood sample:
Patient
Normal values
Glucose (mmol/L)
2.8
3.9 – 5.6
Lactate (mmol/L)
6.6
0.56 – 2.0
Pyruvate (mmol/L)
0.43
0.05 – 0.10
Free fatty acids (mmol/L)
1.6
0.3 – 0.8
Triglycerides (g/L)
3.15
1.5
Total ketone bodies (mg/L)
400
30
pH
7.25
7.35 – 7.44
Total CO2 (mmol/L)
12
24 - 30
A liver biopsy specimen revealed bulging and dilated hepatic cells, the portal areas were
compressed and shrunken, and no inflammatory reaction.. Glycogen content was 11g/100 g
of liver (normal up to 8%), and lipid content was 20.2 g/100 g of liver (normal less than
5g). Hepatic glycogen structure was normal.
The following are results of enzyme assays performed on the liver biopsy tissue:
Enzyme
Patients (units per
gram of liver N)
Glucose-6- phosphatase
22
Glucose-6- phosphate dehydrogenase
0.07
Phosphoglucomutase
27
Phosphorylase
24
Fructose- 1,6 bisphosphatase
8.4
159
Normal range
(units per gram of liver N)
214 ± 45
0.05 ± 0.13
25 ± 4
22 ± 3
10 ± 6
Faculty of Medicine
Biochemical Basis of Medicine I
By the end of this tutorial the student will be able to:
1. Describe the normal structure of hepatic glycogen.
2. Name the enzyme defect in Von Gierke’s disease.
3. Outline the tissues that might be expected to accumulate excessive amounts
of glycogen in Von Gierke’s disease.
4. Match the changes in this structure if there is deficiency in branching
enzyme.
5. Explain the reasons for the fasting hypoglycemic episodes in Von Gierke’s
disease.
6. Relate the elevated free fatty acids, ketonemia and metabolic acidosis in
this disease.
7. Predict and explain the result of continuous parenteral feeding.
8. Recognize the nature of acidosis and its causes in a case of Von Gierke’s
disease.
1. What is a normal structure for hepatic glycogen?
2. What changes in this structure would accompany a deficiency in branching
enzyme?
3. Which other tissues might be expected to accumulate excessive amounts of
glycogen?
4. Explain the reasons for the fasting hypoglycemic episodes.
5. To what might be ascribed (a) the elevated free fatty acid,
ketonemia, and (c) the metabolic acidosis?
160
(b) the
Faculty of Medicine
Biochemical Basis of Medicine I
6. What would you predict would be the result of continuous parenteral
feeding? Explain.
7. What is the nature of acidosis
1- Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition,
Champe & Harvey
2. Supplementary Texts And Resources: Medical Biochemistry, Baynes
and Dominiczek, 1st edition, Mosby
Try to access CD-ROM series about carbohydrate metaboliosm.
1. en.wikipedia.org/wiki/Glycogen_storage_disease_type_1
2. www.ncbi.nlm.nih.gov/entrez/dipomim.cgi/id=232200
3. www.merck.com/mmhe/sec 23/ch 282/ ch 282b
4. pediatrics.aappublications.org/cgi/content/abstract/16/6/785
161
Faculty of Medicine
Biochemical Basis of Medicine I
• Learning issues
At the end of the first session you will be able identify the learning issues which
related to Von Gierke’s disease
Try to summarize these learning issues in the table below. We recommend you to
learn about these issues. This will help you to solve the problem in the next
session.
Learning issues
Notes
…………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
…………
……………………………………………………………
162
Faculty of Medicine
Introduction
Biochemical Basis of Medicine I
Tutorial # 7
Galactosemia
During this week you will work through the case of Galactosemia
A boy patient was the first child of healthy parents without known consanguinity.
Delivery was normal and birth weight was 3.78 kg. From the third day of life the child
developed an increasing degree of jaundice and at the same time became indolent and
difficult to feed. No blood group incompatibility could be demonstrated. At 6 days of age
he had a serum bilirubin of 504 µmol/L, and his weight was 15% below normal weight.
Muscular tonus was increased, and the patient later began to convulse. Serum bilirubin
concentration remained high inspite of frequent exchange blood transfusion. On the the
ninth day of life the boy began vomiting, liver enlargement was noted, and the cerebral
symptoms became accentuated.
A positive test for reducing sugars in urine had already been obtained in the sixth day
after birth, which also obtained on the seventh day, while a test for glucose in urine was
negative. Hereditary galactosemia was then suspected, and special tests that were
performed on the eighth day of life confirmed the diagnosis:
Hemoglobin
12.4 mmol/L (200 g/L)
AST
299 U/L
ALT
202 U/L (normal after seventh day)
Bilirubin (max)
549 µmol/L (at seventh day)
Glalactose-1-P uridyl transferase
0 (normal 2 – 31 units/g of hemoglobin)
(in erythrocytes)
Milk feeding was stopped on the ninth day, and it was replaced by intravenous glucose
administration. From the tenth day of life, galactose-free diet was introduced. With this
treatment the patient improved dramatically.
By the end of this tutorial the student will be able to:
1. Summarize the metabolic pathway of galactose in the body.
2. Describe the biochemical defect usually found in galactosemia.
3. Predict the biochemical effects of galactosemia.
4. Illustrate the alternate source of galactose.
5. Explain the ability of galactosemic mother to produce lactose in her milk.
6. Interpret the laboratory results obtained from a galactosemic patient.
7. Distinguish the differences if galactosemia is due to galactokinase deficiency.
163
Faculty of Medicine
Biochemical Basis of Medicine I
1. Illustrate the pathway for galactose metabolism
2. What is the biochemical defect in classic galactosemia?
3. What are the biochemical effects of galactosemia?
4. Is there an alternate source of tissue galactose for patient on a galactose-free
diet?
5. Would a homozygous galactosemic mother be able to produce lactose in her
milk ?
6. How would a D-galactose tolerance curve have appeared if it had
(unfortunately) been given to the patient?
7. What are the interpretations of the laboratory results?
8. What differences would have been noted if the deficient enzyme had been
galactokinase
1- Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition,
Champe & Harvey P: 107 - 114
2. Supplementary Texts And Resources: Medical Biochemistry, Baynes
and Dominiczek, 1st edition, Mosby
Try to access CD-ROM series about carbohydrate metaboliosm.
1. www.savebabies.org/diseasedescriptions/galactosemia.php
2. www.nlm.nih.gov/medlineplus/ency/article/000366.htm
3.www.wikipedia.org/wiki/galactosemia
4.www.nvbi.nlm.nih.gov/entrez/dispomim.cgi/id=230400
5.www.merck.com/mmpe/sec19/ch296/ch296d.html
6. children.webmd.com/Galactosemia-Test
164
Faculty of Medicine
Biochemical Basis of Medicine I
• Learning issues
At the end of the first session you will be able identify the learning issues which
related to Galactosemia
Try to summarize these learning issues in the table below. We recommend you to
learn about these issues. This will help you to solve the problem in the next
session.
Learning issues
Notes
…………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
…………
……………………………………………………………
165
Faculty of Medicine
Introduction
Biochemical Basis of Medicine I
Tutorial # 8
Hereditary Fructose Intolerance
During this week you will work through the case of Hereditary Fructose
Intolerance
A child had nausea, vomiting, and symptoms of hypoglycemia: sweating, dizziness, and
trembling. It was reported that these attacks occurred shortly after eating fruit or cane
sugar. This was resulting in a strong aversion to fruits, and the mother was therefore
providing large supplementations of multivitamin preparations. The child was below
normal weight and was an only child who had been breast fed, during which time none of
these symptoms was evident. The clinical findings included some cirrhosis of the liver, a
normal glucose tolerance test, and reducing substances in the urine that did not react
positively with glucose test papers, in which glucose oxidase was used as the basis for test.
A fructose tolerance test was ordered, using 3 g fructose /m2 of surface, given
intravenously in a single, rapid push. Within 30 minutes the child displayed the symptoms
of hypoglycemia. Blood glucose analysis confirmed this and revealed that the
hypoglycemia was greater after 60 to 90 min. Fructose concentration reached a maximum
after 15 min and gradually decreased to zero in 2 ½ hr. Phosphate concentration fell 50%
and AST and ALT elevation were noted after 1 ½ hr. The urine was positive for fructose.
By the end of this tutorial the student will be able to:
1. Summarize the metabolic pathway of fructose in the body.
2. Name the enzyme defect in a patient with hereditary fructose intolerance.
3. recognize the biochemical consequences of deficiency of this enzyme.
4. Explain the elevation noted for AST and ALT in fructose tolerance test.
5. Tell why serum concentration of phosphate drops in fructose intolerance.
6. Explain why the symptoms of hypoglycemia are not found in essential
fructosuria.
7. Show the consequences of deficiency of phosphofructokinase in patient with
hereditary fructose intolerance.
8. Discover the manifestations of inhibition of fructokinase enzyme caused by
fructose-1-phosphate in a patient with hereditary fructose intolerance.
166
Faculty of Medicine
Biochemical Basis of Medicine I
1. Illustrate the metabolic pathway of fructose in the body
2. Explain why the fructose concentration in the blood remained elevated for an
extended period.
3. Explain the elevation noted for AST and ALT in the fructose tolerance test.
4. Why are the symptoms of hypoglycemia not found in essential fructosuria?
5. What would be the consequences of a deficiency of phosphofructokinase in the
patient?
1- Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition,
Champe & Harvey
2. Supplementary Texts And Resources: Medical Biochemistry, Baynes
and Dominiczek, 1st edition, Mosby
Try to access CD-ROM series about carbohydrate metaboliosm.
1. www.pennhealth.com/ency/article/000359.htm
2. www.nlm.nih.gov/medlineplus/ency/article/000359
3. ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=229600
4.www.merck.com/mmpe/sec23/ch282/ch282b.html
167
Faculty of Medicine
Biochemical Basis of Medicine I
• Learning issues
At the end of the first session you will be able identify the learning issues which
related to Hereditary Fructose Intolerance
Try to summarize these learning issues in the table below. We recommend you to
learn about these issues. This will help you to solve the problem in the next
session.
Learning issues
Notes
…………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
…………
……………………………………………………………
168
Faculty of Medicine
Introduction
Biochemical Basis of Medicine I
Tutorial # ٩
Hyperlipidemias
During this week you will work through the case of Hyperlipidemias
A healthy 25-year-old man presents for a physical examination and is found to have
markedly elevated total cholesterol (350 mg/dl), LDL cholesterol (266 mg/dl) and
triglycerides (300 mg/dl), and low HDL cholesterol (36 mg/dl). He has an unremarkable
physical examination. He is normotensive, a nonsmoker, but with a strong family history of
hypercholesterolemia and premature atherosclerotic coronary artery disease
By the end of this tutorial the student will be able to:
1. Revise cholesterol metabolism & serum lipoproteins metabolism.
2. Be aware of the types of hereditary hyperlipidemias.
3. Recognize why LDL level is increased with familial
hypercholesterolemia.
4. Define the secondary causes of hyperlipidemias
5. Be familiar with the risk factors of coronary artery disease
1. What is the most likely diagnosis?
2. What is the next step after diagnosis?
3. What is the class of medication to be prescribed?
4. What are the possible complications if left untreated?
169
Faculty of Medicine
Biochemical Basis of Medicine I
1- Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition,
Champe & Harvey
2. Supplementary Texts And Resources: Medical Biochemistry, Baynes
and Dominiczek, 1st edition, Mosby
Try to access CD-ROM series about Hyperlipidemias .
1.
2.
3.
4.
http://ull.chemistry.uakron.edu/biochem/18/
http://www.dentistry.leeds.ac.uk/biochem/thcme/lipoproteins.html
http://www.biocarta.com/pathfiles/h_LDLPathway.asp
4- nfs.uvm.edu/nfs-new/activities/tutorials/lipid.html
170
Faculty of Medicine
Biochemical Basis of Medicine I
• Learning issues
At the end of the first session you will be able identify the learning issues which
related to Hyperlipidemias
Try to summarize these learning issues in the table below. We recommend you to
learn about these issues. This will help you to solve the problem in the next
session.
Learning issues
Notes
…………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
…………
……………………………………………………………
171
Faculty of Medicine
Introduction
Biochemical Basis of Medicine I
Tutorial # 10
Gallstones
During this week you will work through the case of Gallstones
A 45-year-old female presents with midepigastric pain and nausea/vomiting after eating
fatty meals. She had been told that she had elevated cholesterol levels, her physical
examination is completely normal, but an abdominal ultrasound show few gallstones in the
gall bladder
By the end of this tutorial the student will be able to:
1. Be familiar with bile salt metabolism and regulation
2. Be able to identify where bile salts are synthesized.
3. Define where bile salts emulsify dietary fats.
4. Differentiate between the types of gallstones
5. Be familiar with the clinical picture, complications & treatment of
gallstones
6. Recognize the pathogenetic mechanism of gallstone formation
1. What are gall stones made of?
2. Can gall stones be seen on abdominal X-ray
3. What are the factors needed to consider performing cholecystectomy?
172
Faculty of Medicine
Biochemical Basis of Medicine I
1- Required Texts And Resources: Lippincott Illustrated Reviews, 3rd edition,
Champe & Harvey
2. Supplementary Texts And Resources: Medical Biochemistry, Baynes
and Dominiczek, 1st edition, Mosby
Try to access CD-ROM series about Gallstones
1.http://ull.chemistry.uakron.edu/biochem/18/
2.http://www.uic.edu/depts/mcam/mcbc/handouts/lect26.pdf
3.http://www.nhlbi.nih.gov/guidelines/cholesterol/index.htm
4.http://www.dentistry.leeds.ac.uk/biochem/thcme/cholesterol.html
5. http://www.biocarta.com/pathfiles/h_s1pPathway.asp
173
Faculty of Medicine
Biochemical Basis of Medicine I
• Learning issues
At the end of the first session you will be able identify the learning issues which
related to Gallstones
Try to summarize these learning issues in the table below. We recommend you to
learn about these issues. This will help you to solve the problem in the next
session.
Learning issues
Notes
…………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
………………………………………………………………………
…………
……………………………………………………………
174