A newborn experiences lethargy, vomiting, and tachypnea soon after birth. Laboratory examination reveals a metabolic acidosis with a large anion gap, ketosis, and hypoglycemia. The methylmalonic acid concentration is markedly increased in both the plasma and the urine. Which of the following reactions is most likely deficient in this patient:
Ans. D. Isomerization
Explanation: Catabolism of isoleucine, valine, threonine, methionine, cholesterol, and odd-chain fatty acids leads to formation of propionic acid, which is then converted to methylmalonic acid by biotin-dependent carboxylation. lsomerization of methylmalonyl CoA forms succinyl CoA, which subsequently enters the TCA cycle. Defects in this isomerization reaction lead to the development of methylmalonic acidemia.