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BACKGROUND INFORMATION

Cobalamin is the general term used to describe a group of cobalt-containing compounds (corrinoids) that have a particular structure that contains the sugar ribose, phosphate, and a base (5, 6-dimethyl benzimidazole) attached to the corrin ring. Vitamin B12 can be converted to either of the two cobalamin coenzymes that are active in human metabolism: methylcobalamin and 5-deoxyadenosylcobalamin. Although the preferred scientific use of the term vitamin B12 is usually restricted to cyanocobalamin, in this report, B12 will refer to all potentially biologically active cobalamins.

In the United States, cyanocobalamin is the only commercially available B12 preparation used in supplements and pharmaceuticals. It is also the principal form used in Canada (B. A. Cooper, Department of Hematology, Stanford University, personal communication, 1997). Another form, hydroxocobalamin, has been used in some studies of B12. Compared with hydroxocobalamin, cyanocobalamin binds to serum proteins less well and is excreted more rapidly (Tudhope et al., 1967).

Function

B12 is a cofactor for two enzymes: methionine synthase and L-methylmalonyl-CoA mutase. Methionine synthase requires methylcobalamin as a cofactor for the methyl transfer from methyltetrahydrofolate to homocysteine to form methionine and tetrahydrofolate. L-Methymalonyl-CoA mutase requires adenosylcobalamin to convert L-methymalonyl-CoA to succinyl-CoA in an isomerization reaction. In B12 deficiency, folate may accumulate in the serum as a result of slowing of the B12-dependent methyltransferase. An adequate supply of B12 is essential for normal blood formation and neurological function.

Physiology of Absorption, Metabolism, Storage, and Excretion

Small amounts of B12 are absorbed via an active process that requires an intact stomach, intrinsic factor (a glycoprotein that the parietal cells of the stomach secrete after being stimulated by food), pancreatic sufficiency, and a normally functioning terminal ileum. In the stomach, food-bound B12 is dissociated from proteins in the presence of acid and pepsin. The released B12 then binds to R proteins (haptocorrins) secreted by the salivary glands and the gastric mucosa. In the small intestine, pancreatic proteases partially de-



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