Cobalamin deficiency (Proceedings)


Cobalamin deficiency (Proceedings)

Aug 01, 2011

Cobalamin (vitamin B12) is a cyclic tetrapyrrol that contains a corrin ring with a cobalt atom in the center. Cobalamin is actually made up of a group of compounds and is exclusively derived from bacterial sources. The biologically active forms of this vitamin are methylcobalamin (required for methyl-group transfers) and adenosylcobalamin (required for adenosyl-group transfers), but there are other molecules that belong to this group of vitamins, such as hydroxocobalamin or cyanocobalamin. Cyanocobalamin, does not occur naturally, but is manufactured by bacterial fermentation and cyanide incorporation for treatment of cobalamin deficiency. Cobalamin has important functions in amino acid metabolism and DNA synthesis.

Cobalamin function

Cobalamin is an essential cofactor for several enzyme systems in mammalian species. The first enzyme system, methylmalonyl-CoA mutase, is located in the mitochondria and plays a crucial role in the transformation of propionyl-CoA to succinyl-CoA. Thus, cobalamin plays a major role in the metabolism of several amino acids.

Cobalamin is also important in the transformation of the sulfur-containing amino acids methionine and cysteine. Homocysteine is an intermediary amino acid that is being formed from methionine and is not found in the diet. The transformation of homocysteine to methionine is linked to another metabolically crucial process, the generation of the biologically active tetrahydrofolate from N5-methyltetrahydrofolate. Simplistically, the cobalamin-dependant enzyme methionine synthase transfers a methyl group from N5-methyltetrahydrofolate to homocysteine, which results in tetrahydrofolate and methionine. Thus, this enzyme not only plays a role in the transformation of sulfur-containing amino acids, but may be even more important in the generation of the biologically active tetrahydrofolate, which is involved in the synthesis of both purines and pyrimidines.

Cobalamin absorption

Dietary cobalamin is tightly bound to dietary animal-derived protein. In the stomach, dietary protein is partially digested by pepsin and HCl and cobalamin is being released. However, cobalamin immediately binds to a transporter protein called haptocorrin or R-protein. Haptocorrin is mostly synthesized and secreted by the gastric mucosa. Haptocorrin in turn is digested by pancreatic proteases in the small intestine. Free cobalamin binds to intrinsic factor. In humans, intrinsic factor is mostly synthesized and secreted by the parietal cells of the gastric mucosa, but there is good evidence that in dogs and cats most of intrinsic factor is synthesized and secreted by pancreatic acinar cells. Cobalamin/intrinsic factor complexes are being absorbed by a complex receptor in the microvillus pits of the apical brush border membrane of the ileal enterocytes. Thus, the absorption of cobalamin is an extremely complex system that relies on a multitude of factors and processes. As cobalamin is being absorbed into the intestinal epithelial cells, it dissociates from intrinsic factor and free cobalamin is released into the circulation, where most of it binds to yet another protein, transcobalamin II. The main storage compartments for cobalamin in the body are the liver and the kidney, which maintain serum cobalamin concentrations by releasing cobalamin when needed.

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