MCEE Human

The MCEE gene encodes a protein that is approximately 18 kDa in size and is located in the mitochondrial matrix . The enzyme catalyzes the interconversion of D- and L-methylmalonyl-CoA, which is an essential step in the degradation of branched-chain amino acids, odd chain-length fatty acids, and other metabolites . Specifically, it converts (S)-methylmalonyl-CoA to ®-methylmalonyl-CoA .

Methylmalonyl CoA Epimerase is vital for the catabolism of fatty acids with odd-length carbon chains. During the breakdown of even-chain saturated fatty acids, the β-oxidation pathway shortens fatty acyl-CoA molecules by two carbons per cycle, yielding acetyl-CoA . However, for odd-chain fatty acids, the process results in the formation of propionyl-CoA, which must be converted to succinyl-CoA through a series of reactions . Methylmalonyl CoA Epimerase facilitates one of these critical steps by rearranging (S)-methylmalonyl-CoA to the ® form .

Defective activity of Methylmalonyl CoA Epimerase in humans can lead to severe metabolic disorders, such as methylmalonic acidemia. This condition is characterized by the accumulation of methylmalonic acid in the body, leading to severe acidosis and potential damage to the central nervous system . Current treatments for methylmalonic acidemia include dietary management and, in severe cases, liver or combined liver-kidney transplantation .

The recombinant form of Methylmalonyl CoA Epimerase is used in various research applications to study its structure, function, and role in metabolism. The enzyme’s structure has been resolved by X-ray crystallography, providing insights into its catalytic mechanism and potential therapeutic targets .