The exam will be held
Wednesday 12/12, in SL 140, from 10:30 am until 12:30 pm.
Bring a calculator.
I will make myself available as much as I can for office hours Dec 4-7 and Dec 11 (9am-5pm); however, we will be conducting five faculty candidate interviews during that time, so there will be times I am unavailable for office hours. In addition, I will not be available Monday Dec 10th.
It is a good idea to review past midterms, homework and practice problems in addition to the recommended problems from the text. Here is a link to the final exam from last year.
Here is a link to a key which contains brief answers to the practice exam (will be active by mid-week)
Recommended
Homework Assignments for review
V&V
|
Problems |
|
Chapter 2 |
5, 14 |
|
Chapter 8 |
1, 18-21 |
|
Chapter 9 |
4, 6, 7, 12, 13 |
|
Chapter 10 |
3, 4, 6, 8, 10, 12 |
|
Chapter 12 |
1, 2, 6, 11 |
|
Chapter 14 |
2, 3, 5-7 |
|
Chapter 15 |
2, 3, 6, 9, 14, 18, 19 |
This list is not guaranteed to be comprehensive, but it is a very good idea to review the following topics in preparation for the exam. Underlined topics will be emphasized (i.e. the material covered since midterm II) and will make up roughly 60-70% of the points on the exam; however, the final will be comprehensive!
- basic (not detailed) structural features and properties of biopolymers (DNA, membranes)
- DG = DH - TDS (interactions that contribute to DH and DS in biochemical systems)
- know how to set up and solve problems using DG = DG°’ + RTlnQ
- definitions of thermodynamic stability and kinetic stability
- reaction coordinate diagrams: ability to interpret them; draw them
- application of the Henderson-Hasselbalch equation to predicting the charge on a protein at a given pH
- what is pI?
- amino acids (know structures, 1 letter code, general properties [polarity, charges at pH = 7])
- peptide structure (peptide bond,
location of N- & C- termini)
- protein structure (what
are the common secondary structures, what is tertiary structure, what is a
domain, what is quaternary structure, what are macromolecular assembly
principles)
- Immunoglobulin
– focus on: structure of domains and antigen binding (Complementarity
Determining Regions [CDRs])
- Hemoglobin/Myoglobin
– what are the
general structural features of these proteins?, what is allostery?,
how does allosteric regulation work (via binding of:O2,
BPG, CO2, H+), use of Hill equation to calculate
saturation, what is p50?, what is the definition of cooperativity,
what is the Bohr effect?
- Actin/Myosin – what are thin and
thick filaments (i.e., subunit compositions of each)?, how does Ca2+
ion regulate contraction?
- transition state theory: rate constant: k = Ae-(DG‡/RT) (where DG‡ = energy of activation)
- familiarity with the major strategies that enzymes employ to achieve rate enhancements:
- proximity, GABC, covalent catalysis, TS stabilization, electrostatic stabilization as illustrated in the following examples (you need not know the details [e.g., which residues act as GABC etc.]; rather, know how the example illustrates the concept):
- serine proteases: catalytic triad, oxyanion hole
- lysozyme: GABC, strain
- RNase A: GABC
- Carboxypeptidase A: electrostatic, covalent, GABC (note that the handout I gave you and the problem in your textbook differ on the mechanism for this enzyme…don’t worry about that, if presented with one proposal or the other you should be able to correctly identify the strategies used by the enzyme as shown in that particular proposal).
- Michaelis-Menten model, steady-state model (assumptions, application)
- definitions of Vmax, Km and kcat
- what structural features of an enzyme are most likely to affect KM?
- what structural features of an enzyme are most likely to affect kcat?
- If given a detailed mechanism I expect you to be able to predict whether a given mutation would be most likely to affect Km or kcat, or both.
- graphical analysis (Lineweaver-Burk: what do slope and intercept represent?)
- inhibition models (focus on competitive inhibition, know that uncompetitive, non-competitive involve binding of an inhibitor at some site other than the S binding site)
Regulation: allosteric models, feedback inhibition, zymogens, covalent modification (mainly phosphorylation/dephosphorylation)
Lipids: roles in biological systems, composition (polar head, non-polar tails)
Membranes: fluid mosaic model, composition (lipids, proteins), factors affecting fluidity
Big Ideas:
1) proteins are polyelectrolytes and the charge on a protein (or a specific sidechain) can be described by the Henderson-Hasselbalch equation.
a. Sidechain charge determines:
i. Complementarity between receptor and ligand
ii. Stability of folded vs. unfolded states
iii. Function of GABC’s in enzyme active sites
b. pKa can be modulated by alterations in electrostatic environment (e.g., the Bohr effect)
2) Biomolecules self-assemble. This process is thermodynamically favorable and can be understood by considering changes in enthalpy and entropy for the system and the surroundings
a. The hydrophobic effect is a significant driver of protein folding and also of lipid bilayer formation in membranes
3) Proteins recognize their ligands via complementary interactions
a. Shape (geometric) and electrostatic (includes charge-charge, H-bonds and VdW contacts) complementarity
4) Life is characterized by steady-state conditions, rather than equilibrium conditions.
a. Reactions with unfavorable standard free energies can be made favorable by coupling to a favorable process (such as ATP hydrolysis) and/or maintaining Q < Keq.
b. Most reactions inside cells are thermodynamically favorable; yet, they occur with very slow rates in the absence of a specific catalyst because the reactants are kinetically stable (due to large activation energies).
c. Life occurs within a narrow range of environmental conditions (e.g., pH, ionic strength, temperature, concentrations of metabolites, etc.). Regulation of enzyme activity is critically important for maintaining the conditions that support Life.
5) Enzymes achieve rate enhancements by lowering the energy of the transition state. They do this using principles familiar from organic chemistry and general chemistry. They are complementary to the transition state structure for a given reaction.
This “big ideas” might be useful to you as themes around which you can organize the large amount of information you have encountered in this course. I recommend that you attempt to relate the details of biological phenomena discussed over the quarter to one or more of these “big ideas”. Perhaps you will discover a self-consistent network of connections between these details that will help you in formulating arguments in response to review and exam questions.