Methylmalonyl-CoA mutase (MMUT) (MMUT)

Methylmalonyl-CoA mutase (MMUT) is a nuclear-encoded mitochondrial enzyme that plays a critical role in the catabolism of branched-chain amino acids, odd-chain fatty acids, and cholesterol [1][6]. It catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA, a key step in the propionate pathway that feeds into the tricarboxylic acid (TCA) cycle [6][9]. Mutations in the MMUT gene lead to methylmalonic acidemia (MMA), a severe metabolic disorder characterized by the toxic accumulation of methylmalonic acid and other metabolites, resulting in metabolic acidosis, developmental delays, and organ failure [6][14]. The target "Hepatocyte genomic DNA enabling MMUT expression" refers to therapeutic strategies, such as gene editing or gene therapy, aimed at restoring functional MMUT expression specifically within liver cells [10][16]. For example, the investigational therapy LB-001 uses a promoterless AAV vector to integrate a corrective MMUT gene into the albumin locus of the hepatocyte genome, providing a durable source of the enzyme [10][17]. Other approaches include mRNA-based delivery to hepatocytes to provide transient but repeatable enzyme expression [15][22].

Other names

Methylmalonyl-CoA isomeraseMCMMUTMethylmalonyl-CoA mutase, mitochondrialHepatocyte genomic DNA enabling MMUT expression

Restoration of functional methylmalonyl-CoA mutase enzyme activity through hepatocyte-targeted gene addition, genomic integration, or mRNA-mediated protein expression.