Physiological and molecular aspects of cobalamin transport

Abstract

Minute doses of a complex cofactor cobalamin (Cbl, vitamin B12) are essential for metabolism. The nutritional chain for humans includes: (1) production of Cbl by bacteria in the intestinal tract of herbivores; (2) accumulation of the absorbed Cbl in animal tissues; (3) consumption of food of animal origin. Most biological sources contain both Cbl and its analogues, i.e. Cbl-resembling compounds physiologically inactive in animal cells. Selective assimilation of the true vitamin requires an interplay between three transporting proteins - haptocorrin (HC), intrinsic factor (IF), transcobalamin (TC) - and several receptors. HC is present in many biological fluids, including gastric juice, where it assists in disposal of analogues. Gastric IF selectively binds dietary Cbl and enters the intestinal cells via receptor-mediated endocytosis. Absorbed Cbl is transmitted to TC and delivered to the tissues with blood flow. The complex transport system guarantees a very efficient uptake of the vitamin, but failure at any link causes Cbl-deficiency. Early detection of a negative B12 balance is highly desirable to prevent irreversible neurological damages, anaemia and death in aggravated cases. The review focuses on the molecular mechanisms of cobalamin transport with emphasis on interaction of corrinoids with the specific proteins and protein-receptor recognition. The last section briefly describes practical aspects of recent basic research concerning early detection of B12-related disorders, medical application of Cbl-conjugates, and purification of corrinoids from biological samples.