2XIJ, 2XIQ, 3BIC459417850ENSG00000146085ENSMUSG00000023921P22033P16332NM_000255NM_008650NP_000246NP_000246.2NP_032676Methylmalonyl-CoA mutase (EC 5.4.99.2, MCM), mitochondrial, also known as methylmalonyl-CoA isomerase, is a protein that in humans is encoded by the MUT gene.

Upon entry to the mitochondria, the 32 amino acid mitochondrial leader sequence at the N-terminus of the protein is cleaved, forming the fully processed monomer.

[6] MCM resides in the mitochondria, where a number of substances, including the branched-chain amino acids isoleucine and valine, as well as methionine, threonine, thymine and odd-chain fatty acids, are metabolized via methylmalonate semialdehyde (MMlSA) or propionyl-CoA (Pr-CoA) to a common compound - methylmalonyl-CoA (MMl-CoA).

MCM catalyzes the reversible isomerisation of l‐methylmalonyl‐CoA to succinyl‐CoA, requiring cobalamin (vitamin B12) in the form of adenosylcobalamin (AdoCbl) as a cofactor.

MMA is an autosomal recessive inherited inborn error of metabolism, characterized by recurrent episodes of vomiting, lethargy, profound ketoacidosis, hyperammonemia, and pancytopenia in infancy, and may cause early death.

[6] The murine model has proven an adequate and accurate way of studying the effects of MMA, and potential treatment methods.

The C-Co(III) bond is weak, with a dissociation energy = 109 kJ/mol, and appears to be further weakened through steric interactions with the enzyme.

[16] Binding of histidine-610 residue increases the rate of homolytic β-axial ligand – Co bond breakage by a factor of 1012.

[12][23] MMAA protein favors association with the MCM apoenzyme, and allows for the transfer of the AdoCbl cofactor to the enzyme active site.