Download Week - The University of Sydney

HUMAN BIOCHEMISTRY
BCHM2072 and BCHM2972
SEMESTER 2, 2006
Overview of the two Units of Study
BCHM2072 is a 6-credit point course which consists of 26 lectures (two per week)
and six five-hour practical sessions (one per fortnight). The major aim of the lecture
course is to provide an introduction to metabolism and cell biology and, in particular,
to the way that metabolic processes are integrated between the tissues of our body.
The major function of the practical course is to nurture the technical and generic skills
introduced in MBLG1001 (and, perhaps, BCHM2072 and MBLG2071) and to
introduce some new experiences: eg. working with radioactivity, preparing oral
presentations, and designing assay systems.
BCHM2972 is the Advanced version of the above course. The topics presented are
generally the same but, for six lectures, the BCHM2972 will treat certain concepts at a
more greater depth (eg, at a more mechanistic level). Advanced students will perform
some extension tasks in the practical classes and will have a different examination
paper.
How to qualify for the courses
To qualify for BCHM2072 you must obtain a full pass (>50%) in the first year course,
MBLG1001 (or its pre-2005 equivalent) or MBLG2071. Many of the practical
experiments performed this semeseter are contingent on you being able to handle
basic lab equipment and perform rudimentary biochemical calculations (ie, all the
things tested in the MBLG skills tests).
To qualify for BCHM2972 you need distinctions in one of the previous
MBLG/BCHM units of study AND distinctions in Junior Chemistry. However, let us
know if you feel that you would like to be considered for entry with lower
qualifications.
BCHM2072/2972 Human Biochemistry
Semester 2, 2006
Page 1
Lectures
The lectures will be in Chemistry Lecture Theatre 1 at 10 am every Wednesday and
Friday of the Semester. Every ODD Friday (starting Week 3), the Advanced class
goes to Room 471 in the Biochemistry Building.
Lecturers
Your lecturers for this semester are :
A/Prof Gareth Denyer (Room 715, Ph 9351 3466, [email protected])
Dr Simon Easterbrook Smith (Room 605, Ph. 9351 3905, [email protected])
Vanessa Gysbers (Room 711, Ph 9356 5352 [email protected])
All the lecturers are available throughout the semester for consultation. Although it is
acceptable to call on them at any time, it would be wiser to phone or email them to
arrange an appointment.
It is important to remember that the examination questions relating to specific topics
will be set by the lecturers who delivered the relevant lectures. Therefore, if you
experience any difficulties with any part of the lecture course, discuss the matter first
with the person who gave the lectures.
For other problems and inquiries, contact the Course Coordinator, A/Prof Gareth
Denyer.
Lecture Topics
An overview of the lectures in this course is given below. A more detailed description
of the content of each lecture will be put on the BCHM2072 web page as the course
progresses. Be warned that the precise content and emphasis of each lecture may vary
slightly from that described below. It is essential that you revise from a full set of
lecture notes, NOT just this syllabus.
Similary, the timetable is meant as a general guide to the order of material covered.
Some topics may require more time than that allocated in this table while other topics
may take less. USE THIS LIST AS A GUIDE ONLY!
BCHM2072/2972 Human Biochemistry
Semester 2, 2006
Page 2
ENERGY BALANCE (Weeks 1 - 3)
Introduction to metabolism
Anabolism and Catabolism
Linkage of synthesis and degradation through ATP and NADH
General facts regarding ATP
Overview of Catabolism
General structure of fuel molecules: fats and carbohydrates
Strategies of energy extraction: fuel transport, cytoplasmic trapping, use of carriers,
hydrogen stripping, generation of proton gradients and the sythesis of ATP.
Coupling.
Inderdependence of electron transport and oxidative phosphorylation.
Relationship between energy expenditure and fuel oxidation
An amusing role play to illustrate coupling.
Inhibitors of ATP generation.
Uncoupling fuel oxidation from ATP synthesis. Dinitrophenol and uncoupling
proteins.
Development of anti-obesity drugs and nature's radiator: brown adipose tissue.
The molecular machinery of fuel oxidation and ATP synthesis
Details of the electron transporters (NAD, FAD) and the structure of the electron
transport chain.
Electron transporting complexes and the movement of electrons between and within
them.
The mechanism of proton pumping.
The structure and function of the F1F0ATPase
Stoichometry of ATP sythesis.
Whole body energy balance
Measurement of whole body energy expenditure
Regulation of metabolic rate
The balance between energy intake and energy expenditure
BCHM2072/2972 Human Biochemistry
Semester 2, 2006
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CARBOHYDRATES (Weeks 4 - 6)
Carbohydrate sources , digestion and tissue uptake
Basic overview of carbohydrate structure
Simple sugars (eg, glucose and fructose), disaccharides (maltose, lactose and sucrose)
and polysaccharides (amylose, amylopectin)
Dietary sources, digestion and absorbtion
Introduction to blood glucose homeostasis: keeping blood [glucose] at 5 mM
The Glycemic Index
Glucose disposal: Glucose transport into tissues. GLUTs. Tissue differences.
Trapping of glucose inside the cell.
Carbohydrate chemistry.
Nomenclature: chain lengths, aldose/ketose, formation of rings/open chains,
numbering, stereochemistry (D/L forms), anomeric forms
Drawing carbohydrate structures
Sugar tests: reducing sugars.
Formation of disaccharides: glycosidic bonds.
Polysaccharides: tertiary structure of cellulose and starch
Fates of glucose – Glycogen
Overview of glycolysis, glycogenesis, lipogenesis and pentose phosphate pathway.
Importance of rate limiting enzymes in determining fate of G6P. Properties of flux
generating steps.
Hormonal stimulus for glucose transport and glycogenesis complemented by energy
charge stimulus for glycolysis.
Details of regulation of glycogen synthase and molecular mechnanism of glycogenic
pathway.
Liver/Muscle differences in glycogen synthesis.
Glucokinase vs Hexokinase
Fate of fructose.
BCHM2072/2972 Human Biochemistry
Semester 2, 2006
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Fates of glucose - Lipogenesis
Generation of acetyl CoA and hormonal activation of pyruvate dehydrogenase
activation of acetyl CoA carboxylase for formation of malonyl CoA
Hormonal and metabolic regulation of acetyl CoA carboxylase
Fatty acyl synthase - detailed mechanism
Formation of triglyceride: source of glycerol
transport of acetyl CoA into the cytoplasm: ATP-citrate lyase and inhibtors
Generation of reductant (NADPH) by pentose phosphate pathway
Desatruation of fatty acids.
FAT and PROTEIN (Week 6-7)
Dietary Fat: sources, digestion and transport
Fat digestion: bile salts, micelle formation, lipases
Fat substitutes and lipase inhibitors
Chylomicrons - Structure of lipoproteins - transport of fat to the tissues via lymphatic
system
Uptake of fat into tissues: lipoprotein lipase. Reesterification of fatty acids and
glycerol for fat storage
Cholesterol metabolism
Cholesterol absorbtion. Cholesterol transport: chylomicron remnants, VLDL, LDL
LDL receptors: consequences of defect.
HDL: reverse cholesterol transport
Strategies for lowering blood [cholesterol]
Protein metabolism
Protein intake. Essential vs non-essential amino acids. Consequences of inadequate
intake.
Transamination and processing of carbon skeletons
Phenylketouria
Funneling of nitrogen to liver for nitrogen excretion and Urea synthesis
BCHM2072/2972 Human Biochemistry
Semester 2, 2006
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CELL SIGNALING (Weeks 8 -9)
Protein Trafficking
Biosynthesis of extra-cellular proteins; roles of signal peptides, SRP and the
translocon
Folding, quality control and glycosylation of proteins in the ER
Intrinsic and peripheral membrane proteins, protein and lipid anchors
Processing cellular messages
Overview of signal transduction: autocrine, paracrine, endocrine and contact
signalling signal delivery by protein kinases and phospholipases, adaptor proteins,
cross-talk and divergence between pathways
Types of receptors: 7-TMS receptors, protein tyrosine kinase (PTK) receptors,
cytokine receptors, ligand-gated ion channels.
Messaging systems
Coupling of the JAK/STAT pathway to cytokine receptors; roles of PTKs and SH2
domains
Activation of the MAP kinase cascade by growth factor receptors; adaptor proteins,
roles of SH2 and SH3 domains.
Phospholipase C and signal transduction; production of IP3 and DAG, mobilization of
Ca2+, activation of protein kinase C. Role of protein kinase C in activation of NFKB.
Mechanism of nuclear import of NFKB.
G protein-coupled receptors; roles of G proteins. Activation of adenyl cyclase and
protein kinase A. Pathological consequences; cholera toxin.. Short-term and long-term
effects of protein kinase A; effects on glycogen metabolism, activation of CREB
BCHM2072/2972 Human Biochemistry
Semester 2, 2006
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STARVATION (Weeks 10-11)
Starvation - The Post-absorbtive period
Tissue requirements vs fuel stores. Special focus on brain requirements.
Mobiliisation of liver glycogen
Activation of liver phosphorylase by glucagon - control by reversible phosphorylation
cAMP and protein kinase amplification cascade
Starvation - The first 48 hours
Lipolysis from adipose tissue: role of PKA and phosphodiesterase
Use of fatty acids by muscle. Introduction to the beta-oxidation pathway.
Generation of acetyl CoA and the inhibition of pyruvate dehydogenase
The Glucose-Fatty Acid cycle and glucose conservation
Starvation - Extended
Delivery of amino acid skeletons. Proteolysis and deamination.
The glucose accounting sheet. Need for ketogenesis.
Use of ketone bodies by tissues
The steady state of long term starvation
Starvation - Details of the Key Pathways
The mechanism of beta-oxidation. Oxidation of unsaturated fatty acids.
Mechanism of ketone body production.
The gluconeogenic pathway. Key enzymes, substrates and control
BCHM2072/2972 Human Biochemistry
Semester 2, 2006
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EXERCISE (Week 12)
Exercise - Light exercise to moderate exercise
Muscle fibre types: muscle role of Ca2+ and ATP
Provision of ATP by oxidative phosphorylation
Fuel selection during walking: gradual dominance of fatty acid oxidation
Running - increasing the rate of the Krebs cycle, electron transport and oxidative
phosphorylation.
The biochemistry of the Krebs Cycle.
Exercise - competitive intensitiy
More intense exercise. Glycogenolysis in muscle.
Importance of glycogen during intense exercise.
Glycogen supercompensation.
Strategies for glycogen sparing and glucose conseveration
Ergogenic aids for the marathon runner.
Exercise - sprinting
Glycolysis and its regulation
Energy charge, Creatine phosphate
Lactate and acid accumulation
Ergogenic aids for the sprinter
DIABETES (Week 13)
Juvenile Onset Diabetes Mellitus
Symptoms of Type I Diabetes
Metabolic consequences of hypoinsulininemia
Overview of cause of IDDM
Treatment of IDDM. Long term complications of diabetes
Maturity Onset Diabetes Mellitus
Insulin resistance: definition and measurement; The Euglycemic Clamp.
Defective insulin secretion
Treatment of NIDDM.
BCHM2072/2972 Human Biochemistry
Semester 2, 2006
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TIMETABLE
Week
Beginning
Wednesday
Friday
1
24th July
Introduction
Energy Balance
2
31st July
Energy Balance
Energy Balance
th
3
7 Aug
Energy Balance
Energy Balance *
4
14th Aug
5
Carbohydrate
Carbohydrate
st
Carbohydrate
Carbohydrate *
th
21 Aug
6
28 Aug
Carbohydrate
Fat
7
4th Sept
Fat
Protein *
th
8
11 Sept
Cell Signaling
Cell Signaling
9
18th Sept
Cell Signaling
Cell Signaling *
Break
25th Sept
Holiday
Holiday
nd
10
2 Oct
Starvation
Starvation
11
9th Oct
Starvation
Starvation*
12
th
Exercise
Exercise*
rd
Diabetes
Diabetes*
13
16 Oct
23 Oct
An asterix shows the planned dates of the Advanced lectures. However, the exact
sessions on which the BCHM2072 and BCHM2072 students will have different
classes may change nearer the date.
Text Books
It is assumed that you have purchased a recent edition of a general Biochemistry text
by now. Indeed, any up-to-date Biochemistry text-book will give fundamental
coverage of metabolism and will be reasonably sufficient for this course – especially
as materials will be provided during the semester.
However, your recommended text-book for this semester is Voet, Voet and Pratt Fundamentals of Biochemistry: Life at the Molecular Level, 2nd edition. Although we
do not lecture ‘from’ this book, we will try and refer to it as much as possible..
An additional benefit to buying the book is that it gives you access to the web site that
accompanies the book. The web site contains many animations, diagrams, practice
questions, study aids, etc, etc.
BCHM2072/2972 Human Biochemistry
Semester 2, 2006
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Internet Resources
The Human Biochemistry web page is at: http://www.mmb.usyd.edu.au
Follow the links to Student Information > Current Students > BCHM2072.
This site will be updated regularly as the course progresses. Please note, though, that
the laboratory printers are NOT to be used for printing out WWW files. Any abuse of
this will be reported to A/Prof Denyer! Scary hey!
THE PRACTICAL COURSE.
General Arrangements
The practicals are not specifically designed to complement the material taught in
lectures but are mainly designed to teach you a wide range of scientific and generic
skills (ie, the sorts of skills much loved by employers).
Laboratory classes run from 1.00 pm to 6.00 pm Tuesday to Friday. Students have
been allocated practical groups using information provided by Student Records.
Practical classes are done on a FORTNIGHTLY cycle – and you will be allocated to
either an ODD or EVEN cycle.
There will be no practical classes in the first week of the semester. HOORAY!!! Thus
you will do your pracs in either weeks 2, 4, 6, 8, 10 & 12 or in Weeks 3, 5, 7, 9, 11
and 13.
You may have the same demonstrator as in MBLG1001/2071 or BCHM2072 although we endeavour to minimise this. If you feel disadvantaged by having the
same demonstrator twice see A/Prof Denyer.
How do I change my practical day?
If you will not be able to attend on your allocated practical day, you must notify us
well BEFORE your first practical session (ie, early in Week 1). You MAY be
allowed to switch days but you must provide reasons for wanting to change IN
WRITING. YOU MUST NOT TAKE IT UPON YOURSELF TO CHANGE
PRACTICAL GROUPS. Group change requests must be channelled through EMAIL
to A/Prof Denyer. Students must cite their SID, old day/cycle, preferred new
day/cycle and reasons for wanting to change.
BCHM2072/2972 Human Biochemistry
Semester 2, 2006
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When can I use the Computer Facility?
There are 20 Macintosh computers in the laboratory. You may use the computer
facility on any day from 9.30 am - 5 pm. Computers may ONLY be used for
Biochemistry-specific work. In particular, the printers must NOT be used to print out
any material that is not directly connected with your practical class. Students
undertaking a practical have priority during class times.
What happens if I miss some Practical Classes?
As with previous MBLG and BCHM courses, you MUST attend >90% of practical
classes, even with medical certification. This means that if you miss more than one
class, you cannot expect to pass the practical course. It is, however, possible to make
up classes and this can be arranged with A/Prof Denyer or the lab class supervisor.
DO NOT TAKE IT UPON YOURSELF TO OMIT AND/OR ENTER SPECIFIC
SESSIONS. You must get permission in writing to attend make-up classes.
Where do I get a Practical Manual?
The resource manual for the course is available from the University Co-op Bookshop
(near the Noel Martin Recreation Centre) at a cost of about $20. . You will require
this by the first practical class ie. Week 2 or 3.
What else do I need?
You should attend your first practical class with your own copy of the lab manual, a
laboratory coat, a hard bound laboratory notebook and a waterproof marking pen.
What if I need help with some part of the practical course?
Your first port of call should be your demonstrator or, if they are not available, A/Prof
Denyer.
BE VERY SURE to read the section in your MBLG1001 Resource Manual on
Laboratory SAFETY. Attendance in the labs is conditional on your doing this. Since
you must have done MBLG1001 to enter this course, the information is not duplicated
here. However, if you do not have a copy, please ask A/Prof Denyer.
BCHM2072/2972 Human Biochemistry
Semester 2, 2006
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ASSESSMENT
This School supports and adheres to the Academic Board and Faculty of Science
recommendations regarding the award of merit grades. Therefore, ALL marks are
RAW until your final grade is ratified by the Faculty. In other words, marks for any
component can be scaled up or down at Departmental and/or Faculty Examiners
meetings.
The lecture (theory) component of the course is worth 50% of the final assessment
with the practical components contributing 50% to the final mark. However, a pass in
both sections is essential.
The lecture (theory) component of the course will be assessed by two hours worth of
questions in the end of semester exam
The practical component of the course will be assessed
a)
by your laboratory work (including your lab notebook, presentations, and
assay design assignments) with the exact contribution of these individual components
being detailed in the practical resource manual. However, in total, ‘practical work
comprises 50% of the final practical mark.
b)
One hours worth of questions in the end of semester exam. The questions will
be based on concepts, calculations and techniques covered in the labs. This will
contribute 50% to the final practical mark.
ACADEMIC HONESTY
Any submitted reports that appear to have been copied or otherwise plagiarised may
be seen as evidence of academic misconduct and may be subject to an investigation
by the University Registrar. Further information on the Academic Policy of the
University of Sydney is available on the university website
(http://www.usyd.edu.au/ab/policies/). Of particular relevance here is the document
entitled “Academic Honesty in Coursework (plagiarism)”.
BCHM2072/2972 Human Biochemistry
Semester 2, 2006
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SPECIAL CONSIDERATION
It is Faculty of Science policy that there are no Supplementary Examinations for
courses which are only studied for one semester. However, we recognise that sickness
or other misadventures can have an adverse effect on your performance. Therefore,
we have set up the following procedures to ensure that you are not disadvantaged
because of illness or other problems. A copy of the Illness and Misadventure Policy
for the School of Molecular and Microbial Biosciences is located on the School
website.
What you should do if you are sick (or have other problems) DURING the semester.
Applying for special consideration
1. The student obtains an Application for Special Consideration form from the Student
Information Office of the Faculty of Science, or from the Faculty website at
www.science.usyd.edu.au, or from the School of Molecular and Microbial
Biosciences website.
2. The student lodges the original of the application form and originals of any
supporting documentation at the FACULTY Student Information office. Where it is
not possible to obtain original documentations (for example, death certificate or police
report), submission of a certified copy will be permitted. All other forms submitted
must be originals, including the Professional Practitioners Certificate (PPC).
Please note that it is also necessary to provide a copy of the application and all
documentation for each unit of study in which consideration is being sought, to be
certified by the Faculty and forwarded by the student to the School for assessment (ie,
if you are applying for consideration for three units of study, you must submit the
original documentation plus three copies). The Student Information Office will not
make copies of any documentation submitted.
For consideration due to serious illness a student must have a registered medical
practitioner or counsellor complete the PPC, which is attached to the application form.
A Medical Certificate is also acceptable provided that it contains information similar
to that requested on the PPC (that is, it must provide information attesting to the
severity of the illness and its impact on academic performance).
For consideration due to misadventure, a PPC or other form of appropriate
documentation is required which indicates the likely duration and effect of the
misadventure on the student’s performance.
BCHM2072/2972 Human Biochemistry
Semester 2, 2006
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Please note that only the supporting documents provided at the time of initial
application for Special Consideration will be used to assess the request. It will not be
possible to submit further documentation relating to an initial application once an
application has been lodged with the Student Information Office. Only those
circumstances brought to the attention of staff at the time of lodgement will be taken
into consideration when formulating an academic judgment.
3. The Student Information Office checks the application at the time of lodgement to
ensure that a student’s documentation is adequate and, if so, will sign/stamp both the
original application form as well as the student’s copies to confirm lodgement of the
application at the office. The Student Information Office will enter the details
contained on the application form into the Special Consideration database, which will
be used to monitor the progress of the application.
4. The student takes the stamped and dated application form and documentation to the
relevant School Administration Office for assessment. Please note that this must be
done for each Unit of Study for which consideration is being sought.
5. When an academic judgement has been entered into the Special Consideration
database, the Faculty will communicate the decision to the student via an e-mail to the
student’s University e-mail address. It is expected that a response will be received by
the student within seven days of initial application.
What you should do if you miss an EXAM because of sickness or misadventure.
If you are unable to sit an end-of-semester exam, you must apply for Special
Consideration following the procedure outlined above, including submission of
appropriate supporting documentation, within seven days from the date of the exam.
If a student does not sit an examination and is not granted Special Consideration, a
grade of AF (Absent Fail) will result for that examination.
Special Consideration forms should be lodged with the Student Support staff on level
4 of the Biochemistry and Microbiology Building.
BCHM2072/2972 Human Biochemistry
Semester 2, 2006
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If you are granted Special Consideration, you may be permitted to sit for a postponed
examination. It will be held during the week after the regular examination period.
Although this exam will cover the same lecture and practical material as the original
exam, it will contain new questions and may be in a different format. It will
MOST ASSUREDLY NOT BE THE SAME EXAM. Let’s say that again, shall
we….. IT WILL NOT BE THE SAME EXAM. There will be no further testing after
this date.
SIDs of those students eligible to sit this deferred exam will be posted on the School
of Molecular and Microbial Biosciences website. IT IS YOUR RESPONSIBILITY
TO FIND OUT IF YOU ARE ELIGIBLE TO SIT THE DEFERRED EXAM.
Please note that the marks that you get for any exam that you sit will be treated as
final marks.
Good luck and have a good semester!
BCHM2072/2972 Human Biochemistry
Semester 2, 2006
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