adenosylcobalamin

Adenosylcobalamin, also known as coenzyme B12, is one of the two biologically active coenzyme forms of vitamin B12. It is the form in which a 5'-deoxyadenosyl group is bound to the cobalt center of cobalamin, enabling catalytic radical chemistry through cleavage of the Co–C bond to generate a 5'-deoxyadenosyl radical.

In humans, adenosylcobalamin is produced in cells from cobalamin by adenosyltransferase enzymes, using ATP as an energy source. It is the essential coenzyme form for the mitochondrial enzyme methylmalonyl-CoA mutase, which catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA, a key step in the metabolism of odd-chain fatty acids, propionate, and certain amino acids such as valine and isoleucine.

AdoCbl operates together with the other active B12 form, methylcobalamin, which serves as a coenzyme for methionine synthase in the cytosol. The interconversion of cobalamin among its various forms allows cellular metabolism to adapt to different biochemical needs. The radical mechanism of AdoCbl involves homolytic cleavage of the cobalt–carbon bond to generate the adenosyl radical required for substrate rearrangement.

B12 is obtained from animal-derived foods and is stored primarily in the liver. Deficiency or impaired absorption can lead to elevated methylmalonic acid levels and metabolic disturbances, reflecting impaired methylmalonyl-CoA mutase activity. AdoCbl deficiency specifically disrupts propionate and odd-chain amino acid metabolism, with clinical manifestations overlapping other forms of B12 deficiency.