Methylmalonyl CoA epimerase

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methylmalonyl CoA epimerase
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methylmalonyl CoA epimerase
Chr. 2 p13.3
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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 involved in fatty acid catabolism that is encoded in human by the "MCEE" gene located on chromosome 2. It is routinely and incorrectly labeled as "methylmalonyl-CoA racemase". It is not a racemase because the CoA moiety has 5 other stereocenters.

Structure

The "MCEE" gene is located in the 2p13 region and contains 4 exons, and encodes for a protein that is approximately 18 kDa in size and located to the mitochondrial matrix.[1] Several natural variants in amino acid sequences exist. The structure of the MCEE protein has been resolved by X-ray crystallography[2] at 1.8-angstrom resolution.

Function

The MCEE gene encodes an enzyme that interconverts D- and L- methylmalonyl-CoA during the degradation of

odd chain-length fatty acids, and other metabolites. In biochemistry terms, it catalyzes the reaction that converts (S)-methylmalonyl-CoA to the (R) form.[3][4] This enzyme catalyses the following chemical reaction

(S)-methylmalonyl-CoA (R)-methylmalonyl-CoA

Methylmalonyl CoA epimerase plays an important role in the catabolism of

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 (S)-methylmalonyl-CoA by the enzyme Propionyl-CoA carboxylase. Methylmalonyl CoA epimerase then catalyzes the rearrangement of (S)-methylmalonyl-CoA to the (R) form in a reaction that uses a vitamin B12 cofactor and a resonance-stabilized carbanion intermediate.[citation needed] The (R)-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.

Clinical significance

feeding difficulties, and coma
.

References

  1. ^ "MCEE - Methylmalonyl-CoA epimerase, mitochondrial precursor - Homo sapiens (Human) - MCEE gene & protein". www.uniprot.org.
  2. ^ Europe, Protein Data Bank in. "PDB 3rmu structure summary ‹ Protein Data Bank in Europe (PDBe) ‹ EMBL-EBI". www.ebi.ac.uk.
  3. PMID 13934211
    .
  4. PMID 14482843
    .
  5. S2CID 5821956
    .

External links
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