Methylmalonyl CoA epimerase

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methylmalonyl CoA epimerase
Methylmalonyl-CoA epimerase 1JC5.png
Ribbon diagram of methylmalonyl-CoA epimerase from Propionibacterium shermanii. From PDB 1JC5.
EC number
IntEnz IntEnz view
ExPASy NiceZyme view
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
methylmalonyl CoA epimerase
Symbol MCEE
Entrez 84693
HUGO 16732
OMIM 608419
RefSeq NM_028626
UniProt Q96PE7
Other data
EC number
Locus Chr. 2 p13.3

Methylmalonyl CoA epimerase (EC, 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.[1][2] This enzyme catalyses the following chemical reaction

(R)-methylmalonyl-CoA \rightleftharpoons (S)-methylmalonyl-CoA

Role in Fatty Acid Catabolism[edit]

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 B12 cofactor and a resonance-stabilized carbanion intermediate. The (S)-methylmalonyl-CoA is then converted to succinyl-CoA in a reaction catalyzed by methylmalonyl-CoA mutase.

Reaction Mechanism[edit]

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.


  1. ^ 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. PMID 13934211. 
  2. ^ 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. PMID 14482843. 

External links[edit]