Chem. 454/97 EXAM 2

75 PTS.

1. Some texts say that the Urea Cycle "costs" 4 ATP equivalents per nitrogen eliminated. I say that you can actually break even or even make a "profit." Explain in detail how (sketch out the pathways). (10)

2. What are two roles of citric acid in fatty acid biosynthesis? What effect do you think feeding an excess of citric acid in the diet (Grapefruit diet) would have on fatty acid synthesis and breakdown? Explain.(10)

3. Explain why drugs like methotrexate (dihydrofolate reductase inhibitors) are especially toxic to cancer cells? What normal cell types might also be killed (accounting for the bad side effects of chemotherapy)?(10)

4. "Ketone sticks" are sold for detecting of acetoacetate and acetone in the urine at the the Atkins Diet official web site. Why does positive stick test mean "success" in the Atkins diet. That is, explain the origin of these ketones and why the Atkins people would claim that it means you are losing weight. What is the down side of this metabolic state?(10) 

5. OTC (ornithine transcarbamylase) deficiency is a genetically-based urea cycle problem and it used to be fatal in childhood. Now there are (expensive) treatment regimens involving drugs and diet. (15)

a. what urea cycle product(s) would you expect to be lacking (name two)

b. what substances (urea cycle products or others) might be present in excess (name two)?

c. name one substance that you think could be fed to these patients to help reduce the dangers of excess ammonia due to this defect. Explain how.

d. what specific dietary recommendations would you make to improve this condition?

6. Propose a mechanism for the ATP dependent synthesis of CAIR to SAICAR in the purine biosynthesis pathway (below). Show potential general functional groups which you might expect to be at the enzyme active site. Propose (show) an experiment using labeled ¹⁸O which could prove your mechanism. (10)

7. Jaundice is not a disease but a symptom. Give at least two disorders or problems which could produce this same symptom.

8. If you were to design a diet consisting solely of amino acids, which would you choose and why? Realistically, what other nutrients might be necessary to sustain life?