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.
Identifiers
EC number 5.1.99.1
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
methylmalonyl CoA epimerase
Identifiers
Symbol MCEE
Entrez 84693
HUGO 16732
OMIM 608419
RefSeq NM_028626
UniProt Q96PE7
Other data
Locus Chr. 2 p13.3

Methylmalonyl CoA epimerase (EC 5.1.99.1, 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.

References[edit]

  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]