Methylmalonyl-CoA epimerase (MCEE)

Methylmalonyl-CoA epimerase (MCEE) is an enzyme located in the mitochondrial matrix that catalyzes the reversible interconversion of D-methylmalonyl-CoA and L-methylmalonyl-CoA, a critical step in the catabolism of branched-chain amino acids, odd-chain fatty acids, and cholesterol. This reaction enables the formation of succinyl-CoA for entry into the tricarboxylic acid (TCA) cycle. The gene encoding MCEE is located on chromosome 2p13. Deficiency of MCEE due to pathogenic genetic mutations leads to a rare autosomal recessive form of methylmalonic acidemia (MMAuria), typically milder than forms caused by other defects in the pathway. Patients may present with metabolic acidosis, developmental delay, hyperammonemia, and potentially life-threatening metabolic crises in the neonatal period. MCEE is structurally related to the vicinal oxygen chelate (VOC) superfamily and functions as a metalloenzyme, using a divalent metal ion in its active site. There are currently no drugs that specifically target this enzyme[1][2][3]. Additional notes: - While sometimes referred to as a "racemase," this is incorrect; it is properly classified as an epimerase because it interconverts stereoisomers differing at a single chiral carbon and not a simple enantiomeric pair[1]. - Variant forms of the enzyme (missense/nonsense mutations) have been structurally and functionally characterized and correlate with patient phenotypes[3]. - MMA due to MCEE deficiency is rare, and clinical expression can range from asymptomatic to severe metabolic disturbance[2][3].

Other names

Methylmalonyl-CoA epimerase, mitochondrialGLOD2MCEMMCEDL-methylmalonyl-CoA racemase (not accurate, see below)glyoxalase domain containing 2methylmalonyl CoA isomerase

Not applicable; there are no drugs specifically targeting MCEE. Mechanisms in the context of MCEE mutations relate to loss of function, protein misfolding, and impaired d/l-methylmalonyl-CoA interconversion[3].