Corrinoid adenosyltransferase (MMAB) (MMAB)

Corrinoid adenosyltransferase, encoded by the MMAB gene, is a mitochondrial enzyme essential for the conversion of vitamin B12 into its active coenzyme form. It specifically catalyzes the adenosylation of cob(I)alamin to form adenosylcobalamin (AdoCbl) using ATP as the donor (UniProt: Q96EY8). AdoCbl is a mandatory cofactor for methylmalonyl-CoA mutase, an enzyme involved in the metabolic breakdown of certain amino acids and fats. Genetic mutations in MMAB result in cblB-type methylmalonic acidemia, a severe metabolic disorder (NCBI Gene: 326625). This condition leads to the accumulation of methylmalonic acid, causing metabolic acidosis, neurological impairment, and multi-organ failure if untreated. While not a traditional target for inhibition, MMAB is a primary focus for therapeutic restoration via gene therapy or mRNA-based interventions (PubMed: 25533962). Current clinical management involves high-dose hydroxocobalamin to drive any residual enzymatic activity. The enzyme's structure and its interaction with ATP and cobalamin are critical for understanding the molecular basis of the disease and developing targeted stabilizers.

Other names

Cob(I)alamin adenosyltransferaseMitochondrial cobalamin adenosyltransferaseATRcblB

Substrate supplementation to enhance residual enzyme activity or gene/mRNA therapy to restore functional protein levels.