Chapter Summary, Questions Answers - Amino Acid Degradation and Synthesis

CHAPTER SUMMARY

Amino acids whose catabolism yields pyruvate or one of the intermediates of the tricarboxylic acid cycle are termed glucogenic (Figure 20.23). They can give rise to the net formation of glucose in the liver and the kidney. The solely glucogenic amino acids are glutamine, glutamate, proline, arginine, histidine, alanine, serine, glycine, cysteine, methionine, valine, threonine, aspartate, and asparagine. Amino acids whose catabolism yields either acetoacetate or one of its precursors, acetyl coenzyme A (CoA) or acetoacetyl CoA, are termed ketogenic. Leucine and lysine are solely ketogenic. Tyrosine, phenylalanine, tryptophan, and isoleucine are both ketogenic and glucogenic. Nonessential amino acids can be synthesized from metabolic intermediates or from the carbon skeletons of essential amino acids. Essential amino acids need to be obtained from the diet. They include histidine, methionine, threonine, valine, isoleucine, phenylalanine, tryptophan, leucine, and lysine. Phenylketonuria (PKU) is caused by a deficiency of phenylalanine hydroxylase (PAH), the enzyme that converts phenylalanine to tyrosine. Hyperphenylalaninemia may also be caused by deficiencies in the enzymes that synthesize or regenerate the coenzyme for PAH, tetrahydrobiopterin. Untreated patients with PKU suffer from severe intellectual disability, developmental delay, microcephaly, seizures and a characteristic mousey smell of the urine. Treatment involves controlling dietary phenylalanine. Tyrosine becomes an essential dietary component for people with PKU. Maple syrup urine disease is caused by a partial or complete deficiency in branched-chain α-keto acid dehydrogenase, the enzyme that decarboxylates leucine, isoleucine, and valine. Symptoms include feeding problems, vomiting, ketoacidosis, changes in muscle tone, and a characteristic sweet smell of the urine. If untreated, the disease leads to neurologic problems that result in death. Treatment involves controlling dietary leucine, isoleucine, and valine. Other important genetic diseases associated with amino acid metabolism include albinism, homocystinuria, methylmalonyl CoA mutase deficiency, alkaptonuria, histidinemia, tyrosinemia, and cystathioninuria.

Figure 20.23 Key concept map for amino acid metabolism. CoA = coenzyme A.

 
Study Questions:
Choose the ONE best answer.

For Questions 20.1–20.3, match the deficient enzyme with the associated clinical sign or laboratory finding in urine.

A. Black pigmentation of cartilage

B. Cabbage-like odor of fluids

C. Cystine crystals in urine

D. White hair, red eye color

E. Increased branched-chain amino acids

F. Increased homocysteine

G. Increased methionine

H. Increased phenylalanine

20.1 Cystathionine β-synthase

20.2 Homogentisic acid oxidase

20.3 Tyrosinase

Correct answers = F, A, D. A deficiency in cystathionine β-synthase of methionine degradation results in a rise in homocysteine. A deficiency in homogentisic acid oxidase of tyrosine degradation results in a rise in homogentisic acid, which forms a black pigment that is deposited in connective tissue. A deficiency in tyrosinase results in decreased formation of melanin from tyrosine in skin, hair, and eyes. A cabbage-like odor is characteristic of isovaleryl coenzyme A dehydrogenase deficiency. Cystine crystals in urine are seen with cystinuria, a defect in intestinal and renal cystine absorption. Increased branched-chain amino acids are seen in maple syrup urine disease, increased methionine is seen in defects in homocysteine metabolism, and increased phenylalanine is seen in phenylketonuria.

20.4 A 1-week-old infant, who was born at home in a rural area, has undetected classic phenylketonuria. Which statement about this baby and/or her treatment is correct?

A. A diet devoid of phenylalanine should be initiated immediately.

B. Dietary treatment will be recommended to be discontinued in adulthood.

C. Supplementation with vitamin B6 is required.

D. Tyrosine is an essential amino acid.

Correct answer = D. In patients with phenylketonuria, tyrosine cannot be synthesized from phenylalanine and, hence, becomes essential and must be supplied in the diet. Phenylanine in the diet must be controlled but cannot be eliminated entirely because it is an essential amino acid. Dietary treatment must begin during the first 7–10 days of life to prevent intellectual disability, and life-long restriction of phenylalanine is recommended to prevent cognitive decline. Additionally, elevated levels of phenylalanine are teratogenic to a developing fetus.

20.5 Which one of the following statements concerning amino acids is correct?

A. Alanine is ketogenic.

B. Amino acids that are catabolized to acetyl coenzyme A are glucogenic.

C. Branched-chain amino acids are catabolized primarily in liver.

D. Cysteine is essential for individuals consuming a diet severely limited in methionine.

Correct answer = D. Methionine is the precursor of cysteine, which becomes essential if methionine is severely restricted. Alanine is the primary glucogenic amino acid. Acetyl coenzyme A (CoA) cannot be used for the net synthesis of glucose. Amino acids catabolized to acetyl CoA are ketogenic. Branched-chain amino acids are catabolized primarily in skeletal muscle.

20.6 In an individual with the Enzyme 3–deficient form of maple syrup urine disease, why would lactic acidosis be an expected finding?

The three α-keto acid dehydrogenase complexes (pyruvate dehydrogenase [PDH], α-ketoglutarate dehydrogenase, and branched-chain α-keto acid dehydrogenase [BCKD]) have a common Enzyme 3 (E3) (dihydrolipoyl dehydrogenase). In E3-deficient maple syrup urine disease, in addition to the branched-chain amino acids and their α-keto acid derivatives accumulating as a result of decreased activity of BCKD, lactate will also be increased because of decreased activity of PDH.

20.7 In contrast to the vitamin B6-derived pyridoxal phosphate required in most enzymic reactions involving amino acids, what coenzyme is required by the aromatic amino acid hydroxylases?

Tetrahydrobiopterin, made from guanosine triphosphate, is the required coenzyme