Methylmalonyl-CoA mutase, mitochondrial

Methylmalonyl-CoA mutase (MMUT) is a mitochondrial enzyme that catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA, linking branched-chain amino acid and odd-chain fatty acid catabolism to the tricarboxylic acid cycle (UniProt: P22033). The enzyme plays a critical role in organic acid metabolism, and its genetic deficiency causes methylmalonic aciduria (MAMM; MIM 251000), a severe metabolic disorder characterized by neurological dysfunction, developmental delay, and potential early lethality.

In Alzheimer's disease, MMUT expression is upregulated in post-mortem AD brain tissue relative to age-matched controls, with a mean log2 fold-change of +0.61 measured across subcellular fractions in a TMT-labeled proteomics study (Chaparral AD proteomics). This upregulation may reflect altered mitochondrial metabolism or compensatory metabolic shifts associated with neurodegeneration. The elevated levels suggest potential involvement of branched-chain amino acid metabolism dysfunction in AD pathogenesis, though the functional significance of this change requires further investigation.