Download 09.06.11 Intro to Biochemistry w. Clinical

Biochemistry 330
September 6, 2011
•  Introductions
•  Course Outline and Expectations
•  Adverse Childhood Experiences
• Dynamic reach of biochemistry
•  Intro to Biomolecular Structure
BioChem 330 - Course Outline
•  Bio-molecular Structure/Function (I)
–  PROTEINS
•  Structure
–  Chemistry of amino acid building blocks
–  Primary, secondary and tertiary structure
–  Protein folding, thermodynamics and kinetics
–  Predictions of protein folding, dynamics
•  Function
–  Binding ….a tale of two globins (hemoglobin and
immunoglobulin)
BioChem 330 - Course Outline
•  Bio-molecular Structure/Function (I cont’d)
–  NUCLEIC ACID
•  DNA sequence and structure
•  Protein/nucleic acid interactions
–  CARBOHYDRATES
•  Sugars - mono and disaccharides
•  Polysaccharides
•  Glycerides and glycerol
–  FATS AND LIPIDS
•  Chemistry and nomenclature for fatty acids
•  Saturated and unsaturated fatty acids
•  Fluid mosaic model of membrane structure
BioChem 330 - Course Outline
•  Metabolism and Bioenergetics (II)
–  ENZYME CATALYSIS:
•  kinetic constants kcat, Km
•  Catalytic strategies, the serine proteases
–  CATABOLISM (breakdown)
•  Carbohydrates
–  Glycolysis
–  Tricarboxylic Acid Cycle
–  Electron Transport
–  Chemiosmosis and ATPase
•  Fatty acids and amino acids
BioChem 330 - Course Outline
•  Metabolism and Bioenergetics (II)
–  ANABOLISM (building up)
•  Glucose
•  Lipid
•  Cellular Communication/Signal Transduction (III)
–  Intracellular and short range interactions
•  Neurotransmitters
•  Nitric Oxide
–  Intercellular and long range interactions
•  Hormones
–  Small molecule
–  Peptides and proteins
–  Steroid
BioChem 330 - Course Expectations
•  Overall Evaluation:
–  Exams (midterm, final)
~65%
•  Exams will be open book (VVP), open notes and powerpoint printouts,
•  Midterm (30%) is Thursday, October 20th in class
•  Final (35%) is cumulative during final exam period
–  Discussion Section
~20%
–  Additional work
~15%
•  Attendance
•  Structural WIKI (presentation?)
•  Problem Sets
BioChem 330 - Course Expectations
•  Statement of Intellectual Responsibility
–  Exams – no copying, consultation, electronic media
–  All work submitted without citation is your individual work
–  Work can be used from others with citation.
•  Statement of Respect for Persons
–  Discussion Sections
•  Statement of Individual Rights
BioChem 330 – ACE initiative
•  Adverse Childhood Experiences & Biochemistry
–  One novel aspect of this course is our attempt to link theoretical
concepts from lecture with clinical findings and research discoveries that
directly relate to Childhood Stress. The collection of factors known as
“Adverse Childhood Experiences” have been found to affect almost all
aspects of biology, biochemistry, and cellular physiology.
–  Why is this important?
–  How is this relevant?
–  What can I expect to learn?
BioChem 330 - Course Expectations
•  Discussion Sections – Dr. Aronson
•  In our evening sessions, we will meet to discuss papers that bring
together our abstract concepts from class with applied concepts from the
clinical literature. Our leading paper and the first one we will read is a
landmark study in 1998 called the ACE study in which the health status
of 20,000 patients was correlated with childhood stress. As the semester
progresses, we will move from structure to metabolism, illuminating how
every aspect of biochemistry can be dysregulated by chronic stress.
•  Doctor Aronson and Professor O'Hara will in general assign a paper a
week in advance (whenever possible) and will expect participation in an
on-line group discussion prior to the Thursday evening sessions.
Evening sessions will pick up threads from the on-line discussions.
BioChem 330 - Course Expectations
•  Discussion Sections – Dr. Aronson
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You will all be asked to post an original comment AND to respond to another
student's comment. Each student's comment should have at least one response
before you start a threaded discussion.
Guidelines for Response: Pick out some aspect of the paper that you find
especially notable. What we will especially appreciate when possible are those
comments that relate back to material we are studying in lecture. Your comment
should be no more than 100 words and should be posted by 8 AM Tuesday
Guidelines for Comment on a Peer's Response: The length of your response
is up to you. The purpose is to “listen” to each other and learn from each other
through respect, reflection, integration, and critical thinking.
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Ask a thoughtful question.
Comment on what particularly interested you: what particularly resonated with you, expanded your understanding,
inspired you, and so on. Be very specific. (The best way to do this is to copy the part of the student’s you are
commenting on, and paste it into your text before your own comments. That way we can all see what you are
talking about.)
Disagree respectfully on something your classmate wrote, and explain why you feel the way you do. Be specific.
BioChem 330
General Info
•  Fundamentals of Biochemistry: Life at the Molecular Level
–  Text: 3rd Edition Donald Voet, Judith G. Voet, Charlotte W. Pratt,
Wiley University Press January 2008
–  Publisher’s Website: www.wiley.com/college/voet
•  330 CMS: https://www.amherst.edu/academiclife/departments/courses/1112F/CHEM/CHEM-330-1112F
–  Structure: office hours, times and rooms, class roster,
–  Function: e-links to papers, clinical studies, handout
replacements, announcements, structural wikis, discussion
board (responses and comments)
–  Communication: Check your email and I’ll check mine.
Structure and function of biologically important
molecules influence phenomena.
•  structure
Function
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Metabolism
Regulation
Catalysis
Transport
Transcription
Translation
Tight Binding
size
shape
charges
charge distribution
hydrophobicity
amphillicity
location in cell
flexibility
•  a
•  b
•  c
A
B
C
PHENOMENA
DIGESTION
IMMUNE RESPONSE
SIGNAL TRANSDUCTION
CELL DIVISION
MUSCLE CONTRACTION
INFECTION
APOTOSIS
PHOTOSYNTHESIS
BLOOD CLOTTING
PHENOMENON
Structure and function of biologically important
molecules influence phenomena.
organism
100 m
Size Scale of Biological Molecules and Organisms
Our study spans at least ten orders of magnitude in size
Structure and function of biologically important
molecules influence phenomena.
Time Scale of Biological Molecules and Organisms
Our study spans at least fifteen orders of magnitude in time
Structure and function of biologically important
molecules influence phenomena.
Energy Scale of Biological Molecules and Organisms
Our study spans at least four orders of magnitude in energy
Intro To Protein Structure
•  Why start with proteins?
•  Historical: 1951 Predictions
Linus Pauling who, with R. B.
Corey and H. R. Branson
predicted all of the elements of
secondary structure (alpha helix
and beta sheet) based on simple
chemical ideas of VSEPR,
resonance, and hydrogen
bonding (Nobel 1954).
Intro To Protein Structure
•  Why start with proteins?
•  Historical: 1957 Solved Crystal
Structures
–  The first three-dimensional protein
structures (myoglobin and hemoglobin)
were determined by M.F.Perutz and J. C.
Kendrew (Mb at 6 A resolution in 1957,
Nobel Prize in Chemistry in 1962). The
entries are included in the PDB (PDB
codes: 1mbn and 2dhb).
–  Dorothy Hodgkin’s early work on peptide
insulin (Nobel Prize in 1964).
Intro To Protein Structure
•  Why start with the structure of proteins?
•  There is more protein in a cell than anything besides water.
•  e. coli
weight percent
–  water
70%
–  proteins
–  RNA
–  DNA
15%
6%
1%
–  Other
8%
•  How many different kinds of these molecules are there?
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e.coli
humans
HIV-1
•  Proteins
•  RNA
•  DNA
3,000
100+
1
100,000
100+
1
<10
101+
0
Structure/Function
•  What role do proteins play in biological phenomena?
–  Structural role of living organisms (keratin protein in skin, hair, silk)
–  Mechanical role in muscle (actin, myosin, tropomyosin)
–  Catalytic role in enzymes of catabolism and anabolism
(dozens of enzymes in glycolysis, TCA cycle)
–  Storage role (ferritin, holds about 5000 Fe atoms)
–  Synthetic Role (reading and writing enzymes: polymerases, ribosomes)
–  Regulatory Role (calcium regulation by calmodulin, insulin)
–  Intercellular Communication (NOS synthase)
Classic Protein Papers
http://www.pnas.org/misc/classics1.shtml
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1. Pauling, L. & Corey, R. B. Atomic Coordinates and Structure Factors for
Two Helical Configurations of Polypeptide Chains. PNAS, 37, 235-240,
(1951). |Article|
2. Pauling, L. & Corey, R. B. The Structure of Synthetic Polypeptides.
PNAS, 37, 241-250, (1951). |Article|
3. Pauling, L. & Corey, R. B. The Pleated Sheet, A New Layer Configuration
of Polypeptide Chains. PNAS, 37, 251-256, (1951). |Article|
4. Pauling, L. & Corey, R. B. The Structure of Feather Rachis Keratin.
PNAS, 37, 256-261, (1951). |Article|
5. Pauling, L. & Corey, R. B. The Structure of Hair, Muscle, and Related
Proteins. PNAS, 37, 261-271, (1951). |Article|
6. Pauling, L. & Corey, R. B. The Structure of Fibrous Proteins of the
Collagen-Gelatin Group. PNAS, 37, 272-281, (1951). |Article|
7. Pauling, L. & Corey, R. B. The Polypeptide-Chain Configuration in
Hemoglobin and Other Globular Proteins. PNAS, 37, 282-285, (1951). |
Article|