methylmalonyl CoA epimerase

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.{{cite web|url=https://www.uniprot.org/uniprot/Q96PE7|title=MCEE - Methylmalonyl-CoA epimerase, mitochondrial precursor - Homo sapiens (Human) - MCEE gene & protein|website=www.uniprot.org}} Several natural variants in amino acid sequences exist. The structure of the MCEE protein has been resolved by X-ray crystallography{{cite web|url=http://www.ebi.ac.uk/pdbe/entry/pdb/3RMU|title=PDB 3rmu structure summary ‹ Protein Data Bank in Europe (PDBe) ‹ EMBL-EBI|first=Protein Data Bank in|last=Europe|website=www.ebi.ac.uk}} at 1.8-angstrom resolution.

The MCEE gene encodes an enzyme that interconverts D- and L- methylmalonyl-CoA during the degradation of branched-chain amino acids, odd chain-length fatty acids, and other metabolites. In biochemistry terms, it catalyses the chemical reaction that converts (S)-methylmalonyl-CoA to the (R) form:{{cite journal | vauthors = Mazumder R, Sasakawa T, Kaziro Y, Ochoa S | title = Metabolism of propionic acid in animal tissues. IX. Methylmalonyl coenzyme A racemase | journal = The Journal of Biological Chemistry | volume = 237 | pages = 3065–8 | date = October 1962 | issue = 10 | doi = 10.1016/S0021-9258(18)50121-6 | pmid = 13934211 | doi-access = free }}{{cite journal | vauthors = Overath P, Kellerman GM, Lynen F, Fritz HP, Keller HJ | title = [On the mechanism of the rearrangement of methylmalonyl-Co A into succinyl-Co A. II. Experiments on the mechanism of action of methylmalonyl-Co A isomerase and methylmalonyl-Co A racemase] | journal = Biochemische Zeitschrift | volume = 335 | pages = 500–18 | date = 1962 | pmid = 14482843 }}

: (S)-methylmalonyl-CoA $\backslash rightleftharpoons$ (R)-methylmalonyl-CoA

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 (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|date=March 2019}} 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.

Mutations in the MCEE gene causes methymalonyl-CoA epimerase deficiency (MCEED),{{cite journal | vauthors = Bikker H, Bakker HD, Abeling NG, Poll-The BT, Kleijer WJ, Rosenblatt DS, Waterham HR, Wanders RJ, Duran M | title = A homozygous nonsense mutation in the methylmalonyl-CoA epimerase gene (MCEE) results in mild methylmalonic aciduria | journal = Human Mutation | volume = 27 | issue = 7 | pages = 640–3 | date = July 2006 | pmid = 16752391 | doi = 10.1002/humu.20373 | s2cid = 5821956 | doi-access = free }} a rare autosomal recessive inborn error of metabolism in amino acid metabolisms involving branched-chain amino acids valine, leucine, and isoleucine. Patients with MCEED may present with life-threatening neonatal metabolic acidosis, hyperammonemia, feeding difficulties, and coma.

{{Reflist}}

• {{MeshName|methylmalonyl-CoA+epimerase}}

{{Amino acid metabolism enzymes}}

{{Racemases and epimerases}}

{{Enzymes}}

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Category:EC 5.1.99