Methylmalonyl CoA epimerase (EC18.104.22.168, methylmalonyl-CoA racemase, methylmalonyl coenzyme A racemase, DL-methylmalonyl-CoA racemase, 2-methyl-3-oxopropanoyl-CoA 2-epimerase [incorrect]) is an enzyme that converts (S)-methylmalonyl-CoA to the (R) form. This enzyme catalyses the following chemical reaction
Methylmalonyl CoA epimerase plays an important role in the catabolism of fatty acids with odd-length carbon chains. In the catabolism of even-chain saturated fatty acids, the β-oxidation pathway breaks down fatty acyl-CoA molecules in repeated sequences of four reactions to yield one acetyl CoA per repeated sequence. This means that, for each round of β-oxidation, the fatty acyl-Co-A is shortened by two carbons. If the fatty acid began with an even number of carbons, this process could break down an entire saturated fatty acid into acetyl-CoA units. If the fatty acid began with an odd number of carbons, however, β-oxidation would break the fatty acyl-CoA down until the three carbon propionyl-CoA is formed. In order to convert this to the metabolically useful succinyl-CoA, three reactions are needed. The propionyl-CoA is first carboxylated to (R)-methylmalonyl-CoA by the enzyme Propionyl-CoA carboxylase. Methylmalonyl CoA epimerase then catalyzes the rearrangement of (R)-methylmalonyl-CoA to the (S) form in a reaction that uses a vitamin B12cofactor and a resonance-stabilized carbanionintermediate. The (S)-methylmalonyl-CoA is then converted to succinyl-CoA in a reaction catalyzed by methylmalonyl-CoA mutase.
Acting as a general base, the enzyme abstracts a proton from the β-carbon of (R)-methylmalonyl-CoA. This results in the formation of a carbanion intermediate in which the α-carbon is stabilized by resonance. The enzyme then acts as a general acid to protonate the β-carbon, resulting in the formation of (S)-methylmalonyl-CoA.
^Mazumder, R., Sasakawa, T., Kaziro, Y. and Ochoa, S. (1962). "Metabolism of propionic acid in animal tissues. IX. Methylmalonyl coenzyme A racemase". J. Biol. Chem.237: 3065–3068. PMID13934211.
^Overath, P., Kellerman, G.M., Lynen, F., Fritz, H.P. and Keller, H.J. (1962). "Zum Mechanismus der Umlagerung von Methylmalonyl-CoA in Succinyl-CoA. II. Versuche zur Wirkungsweise von Methylmalonyl-CoA-Isomerase and Methylmalonyl-CoA-Racemase". Biochem. Z.335: 500–518. PMID14482843.