(S)-methylmalonyl-CoA hydrolase

(S)-methylmalonyl-CoA hydrolase, also known as methylmalonyl CoA racemase, is an enzyme (EC 5.1.99.1) that catalyzes the racemization of methylmalonyl-CoA, specifically the interconversion between (R)-methylmalonyl-CoA and (S)-methylmalonyl-CoA. This reaction is a crucial step in the metabolic pathway for the degradation of odd-chain fatty acids, branched-chain amino acids (like isoleucine, valine, and methionine), and cholesterol.

The enzyme facilitates the conversion of (S)-methylmalonyl-CoA, which is generated from propionyl-CoA via propionyl-CoA carboxylase and methylmalonyl-CoA epimerase, into its (R) stereoisomer. Only (R)-methylmalonyl-CoA can be further processed by methylmalonyl-CoA mutase, an enzyme that requires vitamin B12 (cobalamin) as a cofactor, to form succinyl-CoA. Succinyl-CoA is then integrated into the citric acid cycle (Krebs cycle) for energy production.

Therefore, (S)-methylmalonyl-CoA hydrolase plays an essential role in ensuring that the substrate is in the correct stereoisomeric form for the subsequent enzymatic reaction in the pathway. A deficiency in this enzyme can lead to methylmalonic acidemia, a metabolic disorder characterized by the accumulation of methylmalonic acid in the blood and urine. The severity of the condition can vary, depending on the extent of the enzyme deficiency.