Reactome: A Curated Pathway Database

Cobalamin (Cbl, vitamin B12) transport and metabolism

Stable Identifier
Homo sapiens
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Vitamin B12 (cobalamin, Cbl) is a water-soluble vitamin with a key role in blood formation and normal functioning of the brain and nervous system. Cbl consists 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 while a number of different species can coordinate with the cobalt atom in the upper axial position. It is the cobalt-corrin ring complex that gives all Cbls a deep red colour. Only bacteria and archaea are able to synthesise Cbl thus humans need a dietary intake to prevent deficiency (Green 2010, Quadros 2010, Watkins & Rosenblatt 2011). A common semi-synthetic form of the vitamin, cyanocobalamin (CNCbl, where a cyanide group is in the upper axial position), is produced from bacterial hydroxocobalamin and used in many pharmaceuticals, supplements and as a food additive. In mammalian cells, Cbl or CNCbl is converted to two active coenzyme derivatives; methylcobalamin (MetCbl) and adenosylcobalamin (AdoCbl). MetCbl is required for activity of the cytoplasmic enzyme methionine synthase, which converts homocysteine to methionine. AdoCbl is required for activity of the mitochondrial enzyme methylmalonyl CoA mutase, which converts L-methylmalonyl-CoA to succinyl-CoA (Seetharam 1999). This pathway outlines the intake, transport and metabolism of Cbl and is assumed to be equally applicable to CNCbl.

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