C485 Exam IV Fall ’14 Answer key
Name___________________
Legible please!
Do not use acronyms. Use structures whenever they are asked for, or appropriate. Your
explanations should be brief. Overly lengthy answers with irrelevant or erroneous
material will receive deductions. GOOD LUCK
1. (10 Pts) The compound shown below is an intermediate in the biosynthesis of
cholesterol that is derived from acetate. Using the numbering system shown below for
acetate, number this compound so it is obvious how it is derived from acetate. Please
draw and number a six carbon intermediate in this pathway.
2. (12pts) There are three pathways for the biosynthesis of phospholipids from
phosphatidic acid. Outline the reactions of these pathways (structures please) and give an
example of a lipid synthesized via each pathway
Synthesis from an activated DAG (p 761)
Synthesis from an activated alcohol (p 763)
Base exchange (p 763)
3. 10. (8 Pts) How many electrons are involved in the oxidations shown below?
a)
4
6
4. (10 pts) Draw the mechanism for thymidilate synthase. What molecule would
function as a useful suicide substrate for this enzyme? Explain how this inhibitor would
work.
5. (14 pts) Draw the mechanism for ribonucleotide reductase. Also, summarize how this
enzyme is regulated.
Regulation p 752
Regeneration of reduced TS p 747
6. (16 pts) Starting with simple sugars, amino acids and one carbon donors, draw the
biosynthetic pathway for GMP biosynthesis. You must show all reactions and include all
reactants and products.
Figure 25.6 and 25.7
7. (12 pts) The carbon backbone of ceramide and sphingosines is assembled in a carboncarbon bond forming reaction. Show the precursors for this reaction, the cofactor
required for this conversion, and a mechanism for any C-C bond forming or C-C bond
making events that take place in this conversion. You must show the entire mechanism
starting from the resting state of the cofactor and regenerating it.
8. (12 Pts) Starting with cholesterol, outline the biosynthesis of the major sex hormones
(estrogen and testosterone). You must use structures. What are the actual sex hormones
that are most active in stimulating a receptor response? Explain how receptors might
differentiate between two molecules that are so similar.
Figure 26.30 and 26.31
You must also show conversion of testosterone to DHT. You may show alternative
pathway through DHEA.
Most active sex hormone are estradiol (E2) and DHT.
Receptors differentiate the molecules base on the A ring, since the D ring is the same.
Differences in the A ring: OH in E2 vs ketone in DHT. Aromatic ring vs. aliphatic ring,
so both sterics and pi stacking will be an issue. Methyl group in DHT will probably not
fit in estrogen binding site of estrogen receptor (exclusionary selectivity).
9. (8pts) Explain the regulatory strategy used to control purine biosynthesis. Make sure
you specifically state which reaction is affected, and what is causing the effect. Explain
the rationale for this type of effect.
Figure 25.15
10. (5 pts total)
a. (1 pt.) Please name the key regulatory step in cholesterol biosynthesis. (may show
enzyme or reaction) HMGCoA reductase
b. (3 pts) State three ways in which the concentration of this enzyme is regulated.
Section 26.3
c. (1 pt) Please describe a way in which the specific activity of the enzyme is regulated.
Section 26.3
11. (10 pts) Nandrolone (structure shown below) is widely used by strength athletes.
What steroid(s) does this molecule mimic? There is one very obvious difference between
this molecule and its natural congeners that gives nandrolone a property that the natural
steroids lack. What is this difference and what is the property? (Hint, identify one of the
structural differences between male and female sex hormones and this may help you.)
Mimics testosterone, but because it lacks a methyl group, cannot be converted in an
estrogen.