Inborn errors of cobalamin absorption, transport and metabolism

Abstract

Cobalamin (Cbl, vitamin B12) is a cobalt-containing vitamin which is synthesized by bacteria and archaea. It can be taken up from food of animal origin, but not from higher plants. Various cobalamins differ in the residue R in the upper axial position of the molecule. In adenosylcobalamin (AdoCbl) R is a 5’-deoxyadenosyl moiety, in methylcobalamin (MeCbl) a methyl group. Common vitamin B12 supplements contain hydroxocobalamin (OHCbl, labelled “the natural form of the vitamin”, with R = OH) or cyanocobalamin (CNCbl, with R = CN). CNCbl does not occur naturally, but is formed during the isolation of bacterial cobalamin (Watkins & Rosenblatt, 2011a). Nominations such as cblA- cblG and cblJ do not refer to special forms of cobalamin, but to enzymes and transport proteins involved in intracellular cobalamin metabolism. Each of those designations refers to a different complementation group and to a defect in cobalamin metabolism caused by mutations in the gene identified for this particular complementation group (Fowler et al., 2008).