Cobalamin adenosyltransferase (MMAB)

Cobalamin adenosyltransferase, primarily encoded by the MMAB gene in humans, is a critical mitochondrial enzyme responsible for the final step in the synthesis of adenosylcobalamin (AdoCbl), an active coenzyme form of vitamin B12 (MedlinePlus, 2011). It catalyzes the transfer of a 5-deoxyadenosyl moiety from ATP to cob(I)alamin and subsequently acts as a molecular chaperone to deliver the newly formed AdoCbl directly to methylmalonyl-CoA mutase (MCM) (UniProt, 2024; PNAS, 2020). This process is essential for the catabolism of branched-chain amino acids, odd-chain fatty acids, and cholesterol within the mitochondria (Wikipedia, 2024). Genetic mutations in the MMAB gene result in the cblB complementation type of methylmalonic aciduria, a life-threatening metabolic disorder characterized by the accumulation of toxic metabolites like methylmalonic acid and homocysteine (MedlinePlus, 2011; NIH, 2023). While current treatment relies on high-dose cobalamin supplementation, such as hydroxocobalamin, to drive residual enzyme activity, research into pharmacological chaperones like Compound V aims to provide more targeted restoration of enzyme stability (Human Molecular Genetics, 2013). Furthermore, gene therapy approaches are being explored to deliver functional copies of the MMAB gene to the liver, potentially offering a long-term cure for affected patients (NIH, 2022). The enzyme's role in lipid homeostasis has also linked its genetic polymorphisms to variations in HDL-cholesterol levels and susceptibility to coronary heart disease (NIH, 2026). In the context of drug development, the enzyme is also being investigated for its ability to process cobalamin-drug conjugates, which could be used for targeted delivery of chemotherapeutics to tumor cells (NIH, 2008). Monitoring of biomarkers such as methylmalonic acid and homocysteine is crucial for assessing the efficacy of these therapeutic interventions (NIH, 2010). Overall, cobalamin adenosyltransferase represents a vital metabolic node with significant implications for both rare genetic diseases and broader cardiovascular health.

Other names

ATP:cob(I)alamin adenosyltransferaseATRcblBCob(I)yrinic acid a,c-diamide adenosyltransferaseMethylmalonic aciduria type B proteinCorrinoid adenosyltransferase MMAB

Catalyzes the ATP-dependent adenosylation of cob(I)alamin to form adenosylcobalamin and facilitates its transfer to methylmalonyl-CoA mutase.