Vitamin B12 (cobalamin) is a water soluble vitamin, consisting of a planar corrin ring coordinating with a cobalt atom through four nitrogen atoms. A 5,6 dimethylbenzamidizole base coordinates with the cobalt atom in the lower axial position. Groups that can coordinate with the cobalt atom in the upper axial position include methyl (methylcobalamin, MetCbl), adenosyl (adenosylcobalamin, AdoCbl) and cyano (cyanocobalamin (CNCbl)). Only bacteria and archaea synthesise cobalamin so humans need a dietary intake to prevent deficiency. Food derived from animals provides cobalamins (RCbl) including MeCbl and AdoCbl. CNCbl, a semi synthetic form of the vitamin produced from bacterial hydroxocobalamin is provided by many pharmaceuticals, supplements, and food additives.
Cbl derivatives function as cofactors in two reactions, AdoCbl in the conversion of homocysteine to methionine and MetCbl in the conversion of L-methylmalonyl CoA to succinyl CoA. Both reactions are essential for normal human function, however, and defects in the steps by which Cbl or CNCbl is taken up from the diet, transported to metabolically active cells, and transformed to AdoCbl and MeCbl are associated with severe defects in blood formation and neural function (Banerjee et al. 2021, Froese & Gravel 2010, Green 2010, Nielsen et al. 2012, Quadros 2010; Seetharam 1999).
The overall process of Cbl utilization is presented here in three parts: its uptake from the diet into gut enterocytes, its release into the blood, circulation within the body (including renal re-uptake), and delivery to the cells where it is used, and its metabolism in those cells to generate AdoCbl and MeCbl.