1.  Keto counterparts. Name the α-ketoacid formed by the transamination of each of the following amino acids. ✓ 1

(a) Alanine

(b) Aspartate

(c) Glutamate

(d) Leucine

(e) Phenylalanine

(f) Tyrosine

2.  A versatile building block. (a) Write a balanced equation for the conversion of aspartate into glucose through the intermediate oxaloacetate. Which coenzymes participate in this transformation? (b) Write a balanced equation for the conversion of aspartate into oxaloacetate through the intermediate fumarate. ✓ 2

3.  Not very discriminating. Glutamate dehydrogenase is considered unusual in that it does not discriminate between NADH and NADPH, at least in some species. Explain why this failure to discriminate is unusual. ✓ 1

4.  Cooperation. How do aminotransferases and glutamate dehydrogenase cooperate in the metabolism of the amino group of amino acids? ✓ 1

5.  Taking away the nitrogen. What amino acids yield citric acid cycle components and glycolysis intermediates when deaminated? ✓ 1

6.  One reaction only. What amino acids can be deaminated directly? ✓ 1

7.  Nitrogen sources. What are the immediate biochemical sources for the two nitrogen atoms in urea? ✓ 1

8.  Counterparts. Match the biochemical on the right with the property on the left. ✓ 1

9.  Completing the cycle. Four high-transfer-potential phosphoryl groups are consumed in the synthesis of urea according to the stoichiometry given in "The Urea Cycle Is linked to Gluconeogenesis", within Section 30.2. In this reaction, aspartate is converted into fumarate. Suppose that fumarate is converted back into aspartate. What is the resulting stoichiometry of urea synthesis? How many high-transfer-potential phosphoryl groups are spent? ✓ 1

10.  A good bet. A friend bets you a bazillion dollars that you can’t prove that the urea cycle is linked to the citric acid cycle and other metabolic pathways. Can you collect? ✓ 1

11.  A precise diagnosis. The result of a reaction between an infant’s urine and 2,4-dinitrophenylhydrazine is positive. 2,4-Dinitrophenylhydrazine reacts with α-ketoacids and suggests the presence of a high concentration of α-ketoacids. Further analysis shows abnormally high blood levels of pyruvate, α-ketoglutarate, and the α-ketoacids of valine, isoleucine, and leucine. Identify a likely molecular defect, and propose a definitive test of your diagnosis. ✓ 2

12.  Line up. Identify structures A–D, and place them in the order that they appear in the urea cycle. ✓ 1

13.  Sweet hazard. Why should phenylketonurics avoid the ingestion of aspartame, an artificial sweetener? (Hint: Aspartame is l-aspartyl-l-phenylalanine methyl ester.) ✓ 1

14.  Déjà vu. N-Acetylglutamate is required as a cofactor in the synthesis of carbamoyl phosphate. How is N-acetylglutamate synthesized from glutamate? ✓ 1

15.  Precursors. Differentiate between ketogenic amino acids and glucogenic amino acids. ✓ 2

16.  Supply lines. The carbon skeletons of the 20 common amino acids can be degraded into a limited number of end products. What are the end products, and in what metabolic pathway are they commonly found? ✓ 2

17.  A sleight of hand. The end products of tryptophan are acetyl CoA and acetoacetyl CoA, yet tryptophan is a gluconeogenic amino acid in animals. Explain.

18.  Negative nitrogen balance. A deficiency of even one amino acid results in a negative nitrogen balance. In this state, more protein is degraded than is synthesized, and so more nitrogen is excreted than is ingested. Why would protein be degraded if one amino acid were missing?

19.  Argininosuccinic aciduria. Argininosuccinic aciduria is a condition that results when the urea-cycle enzyme argininosuccinase is deficient. Argininosuccinate is present in the blood and urine. Suggest how this condition might be treated while still removing nitrogen from the body. ✓ 1

20.  Multiple substrates. In Chapter 8, we learned that there are two types of bisubstrate reactions, sequential and double-displacement. Which type characterizes the action of aminotransferases?

21.  Closely related. Pyruvate dehydrogenase complex and α-ketoglutarate dehydrogenase complex are huge enzymes consisting of three discrete enzymatic activities. Which amino acids require a related enzyme complex for degradation, and what is the name of the enzyme? ✓ 2

22.  Ammonia toxicity. Glutamate is an important neurotransmitter whose levels must be carefully regulated in the brain. Explain how a high concentration of ammonia might disrupt this regulation. How might a high concentration of ammonia alter the citric acid cycle? ✓ 1

23.  Damaged liver. As stated in Chapter 28, excess alcoholic consumption can cause liver damage (cirrhosis). A consequence of liver damage is often ammonia poisoning. Explain. ✓ 1

24.  Inhibitor design. Compound A has been synthesized as a potential inhibitor of a urea-cycle enzyme. ✓ 1



Which enzyme might compound A inhibit?

25.  Fuel choice. Within a few days after a fast begins, nitrogen excretion accelerates to a higher-than-normal level. After a few weeks, the rate of nitrogen excretion falls to a lower level and continues at this low rate. However, after the fat stores have been depleted, nitrogen excretion rises to a high level. ✓ 2

(a) What events trigger the initial surge of nitrogen excretion?

(b) Why does nitrogen excretion fall after several weeks of fasting?

(c) Explain the increase in nitrogen excretion when the lipid stores have been depleted.

26.  Isoleucine degradation. Isoleucine is degraded to acetyl CoA and succinyl CoA. Suggest a plausible reaction sequence, on the basis of reactions discussed in the text, for this degradation pathway. ✓ 2

27.  Enough cycles to have a race. The glucose–alanine cycle is reminiscent of the Cori cycle, but the glucose–alanine cycle can be said to be more energy efficient. Explain.

28.  A serious situation. Pyruvate carboxylase deficiency is a fatal disorder. Patients with pyruvate carboxylase deficiency sometimes display some or all of the following symptoms: lactic acidosis, hyperammonemia (excess NH₄⁺ in the blood), hypoglycemia, and demyelination of the regions of the brain due to insufficient lipid synthesis. Provide a possible biochemical rationale for each of these observations.