Cobalamin (Cbl, vitamin B12) transport and metabolism

Stable Identifier
R-HSA-196741
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Pathway
Species
Homo sapiens
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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.

Literature References
PubMed ID Title Journal Year
19832808 Advances in the understanding of cobalamin assimilation and metabolism

Quadros, EV

Br. J. Haematol. 2010
33797888 Redox-Linked Coordination Chemistry Directs Vitamin B12 Trafficking

Gouda, H, Pillay, S, Banerjee, R

Acc Chem Res 2021
22547309 Vitamin B12 transport from food to the body's cells--a sophisticated, multistep pathway

Rasmussen, MR, Moestrup, SK, Andersen, CB, Nielsen, MJ, Nexø, E

Nat Rev Gastroenterol Hepatol 2012
20185591 Ins and outs of cellular cobalamin transport

Green, R

Blood 2010
10448521 Receptor-mediated endocytosis of cobalamin (vitamin B12)

Seetharam, B

Annu. Rev. Nutr. 1999
21114891 Genetic disorders of vitamin B12 metabolism: eight complementation groups--eight genes

Froese, DS, Gravel, RA

Expert Rev Mol Med 2010
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