Receptor-mediated endocytosis of cobalamin (vitamin B-12)

Dietary cobalamin (Cbl) (vitamin B-12) is utilized as methyl-Cbl and the co enzyme 5'-deoxyadenosyl Cbl by cells of the body that have the enzymes meth ionine synthase and methyl malonyl CoA mutase, which convert homocysteine t o methionine and methyl malonyl CoA to succinyl CoA, respectively. Prior to conversions and utilizations as the active alkyl forms of Cbl, dietary Cbl is absorbed and transported across cellular plasma membranes by two recept or-mediated events. First, dietary and biliary Cbl bound to gastric intrins ic factor (IF) presented apically to the ileal absorptive enterocytes is tr ansported to the circulation by receptor-mediated endocytosis via apically expressed IF-Cbl receptor. Second, Cbl bound to plasma transcobalamin (TC) II is taken up from the circulation by all cells via a TC II receptor expre ssed in the plasma membrane of these cells, and in polarized cells via a TC II receptor expressed in the basolateral membranes. This review updates re cent work and focuses on (a) the molecular and cellular aspects of Cbl bind ing protein Ligands, IF and TC II, and their cell-surface receptors, IF-Cbl receptor and TC II receptor; (b) the cellular sorting pathways of internal ized Cbl bound to IF and TC II in polarized epithelial cells; and (c) the a bsorption and transport disorders that cause Cbl deficiency.