Cob(I)alamin adenosyltransferase (MMAB) (MMAB)

Cob(I)alamin adenosyltransferase (MMAB) is a critical mitochondrial enzyme responsible for the final step in the conversion of vitamin B12 (cobalamin) into its active cofactor form, adenosylcobalamin (AdoCbl) [1]. This enzyme catalyzes the adenosylation of cob(I)alamin, a process essential for the function of methylmalonyl-CoA mutase, which is required for the catabolism of specific amino acids, odd-chain fatty acids, and cholesterol [2]. Mutations in the MMAB gene lead to cblB-type methylmalonic acidemia (MMA), a rare and severe autosomal recessive metabolic disorder characterized by the accumulation of toxic methylmalonic acid and other metabolites [4]. Clinical manifestations include life-threatening metabolic acidosis, hyperammonemia, developmental delays, and progressive organ damage, particularly to the kidneys and brain [4]. While traditional management relies on dietary restriction and vitamin B12 supplementation, modern therapeutic development focuses on restoring enzyme activity through genetic interventions. For example, mRNA-3630 is an investigational mRNA therapy designed to instruct the liver to produce functional MMAB enzyme, thereby addressing the underlying biochemical defect of the disease [3].

Other names

Methylmalonic aciduria (cobalamin deficiency) cblB typeATRCob(I)alamin adenosyltransferase, mitochondrialcblBAdenosylcobalamin transferase

mRNA-based enzyme replacement therapy (e.g., mRNA-3630) delivers the genetic sequence encoding functional MMAB to hepatocytes, allowing the cellular machinery to produce the active enzyme, which restores the synthesis of adenosylcobalamin and facilitates the breakdown of methylmalonyl-CoA [3, 4].