Choose the ONE best answer.
9.1. In this transamination reaction (right), which of the following are the products X and Y?
A. Alanine, α-ketoglutarate
B. Aspartate, α-ketoglutarate
C. Glutamate, alanine
D. Pyruvate, aspartate
Correct answer = B. Transamination reactions always have an amino acid and an α-keto acid as substrates. The products of the reaction are also an amino acid (corresponding to the α-keto substrate) and an α-keto acid (corresponding to the amino acid substrate). Three amino acid α-keto acid pairs commonly encountered in metabolism are alanine/pyruvate, aspartate/oxaloacetate, and glutamate/α-ketoglutarate. In this question, glutamate is deaminated to form αketoglutarate, and oxaloacetate is aminated to form aspartate.
9.2. Which one of the following statements about amino acids and their metabolism is correct?
A. Free amino acids are taken into the enterocytes by a single proton-linked transport system.
B. In healthy, well-fed individuals, the input to the amino acid pool exceeds the output.
C. The liver uses ammonia to buffer protons.
D. Muscle-derived glutamine is metabolized in liver and kidney tissue to ammonia + a gluconeogenic precursor.
E. The first step in the catabolism of most amino acids is their oxidative deamination.
F. The toxic ammonia generated from the amide nitrogen of amino acids is transported through blood as arginine.
Correct answer = D. Glutamine, produced by the catabolism of branched-chain amino acids in muscle, is deaminated by glutaminase to ammonia + glutamate. The glutamate is deaminated by glutamate dehydrogenase to ammonia + αketoglutarate, which can be used for gluconeogenesis. Free amino acids are taken into enterocytes by several different sodium-linked transport systems. Healthy, well-fed individuals are in nitrogen balance, in which nitrogen input equals output. The liver converts ammonia to urea, and the kidneys use ammonia to buffer protons. Amino acid catabolism begins with transamination that generates glutamate. The glutamate undergoes oxidative deamination. Toxic ammonia is transported as glutamine and alanine. Arginine is synthesized and hydrolyzed in the hepatic urea cycle.
For Questions 19.3–19.5, use the following scenario.
A female neonate appeared healthy until age ~24 hours, when she became lethargic. A sepsis workup proved negative. At 56 hours, she started showing focal seizure activity. The plasma ammonia level was found to be 887 µmol/l (normal 5–35 µmol/l). Quantitative plasma amino acid levels revealed a marked elevation of citrulline but not argininosuccinate.
9.3. Which one of the following enzymic activities is most likely to be deficient in this patient?
A. Arginase
B. Argininosuccinate lyase
C. Argininosuccinate synthetase
D. Carbamoyl phosphate synthetase I
E. Ornithine transcarbamylase Correct answer = C. Genetic deficiencies of each of the five enzymes of the urea cycle, as well as deficiencies in N-acetylglutamate synthase, have been described. The accumulation of citrulline (but not argininosuccinate) in the plasma of this patient means that the enzyme required for the conversion of citrulline to argininosuccinate (argininosuccinate synthetase) is defective, whereas the enzyme that cleaves argininosuccinate (argininosuccinate lyase) is functional.