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Choose the ONE correct answer.
9.1. The products X and Y in this transamination reaction (right) are:
A. Alanine, α-ketoglutarate
B. Aspartate, α-ketoglutarate
C. Glutamate, alanine
D. Pyruvate, aspartate

Correct answer = B. Transamination reactions involve an amino acid and an α-keto acid as substrates. The resulting products are also an amino acid (related to the α-keto substrate) and an α-keto acid (related to the amino acid substrate). Commonly encountered amino acid α-keto acid pairs in metabolism include alanine/pyruvate, aspartate/oxaloacetate, and glutamate/α-ketoglutarate. In this particular reaction, glutamate undergoes deamination to form α-ketoglutarate, while oxaloacetate is aminated to produce aspartate.

9.2. The correct statement regarding amino acids and their metabolism is:
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, which is produced by the breakdown of branched-chain amino acids in muscle, is deaminated by glutaminase to form ammonia + glutamate. The glutamate then undergoes deamination by glutamate dehydrogenase, resulting in ammonia + α-ketoglutarate, which can be used for gluconeogenesis. Free amino acids are transported into enterocytes via several different sodium-linked transport systems. In individuals who are healthy and well-fed, the nitrogen input equals the output, maintaining nitrogen balance. The liver converts ammonia to urea, and the kidneys utilize ammonia to buffer protons. Amino acid catabolism commences with transamination, leading to the formation of glutamate. Subsequently, oxidative deamination occurs. Toxic ammonia is transported in the form of 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 initially appeared healthy but became lethargic at approximately 24 hours of age. A sepsis workup yielded negative results. At 56 hours, she began experiencing focal seizure activity. The plasma ammonia level was determined to be 887 µmol/l (normal range: 5–35 µmol/l). Quantitative plasma amino acid measurements indicated a significant elevation in citrulline but not argininosuccinate.

9.3. The most likely enzymatic activity deficient in this patient is:
A. Arginase
B. Argininosuccinate lyase
C. Argininosuccinate synthetase
D. Carbamoyl phosphate synthetase I
E. Ornithine transcarbamylase

Correct answer = C. Genetic deficiencies have been documented for each of the five enzymes involved in the urea cycle, as well as deficiencies in N-acetylglutamate synthase. The presence of elevated citrulline (but not argininosuccinate) in the patient's plasma indicates a defect in the enzyme responsible for converting citrulline to argininosuccinate (argininosuccinate synthetase), while the enzyme that cleaves argininosuccinate (argininosuccinate lyase) remains functional.

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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.