Receptor-mediated endocytosis of cobalamin (vitamin B12)

Dietary cobalamin (Cbl) (vitamin B-12) is utilized as methyl-Cbl and the coenzyme 5'-deoxyadenosyl Cbl by cells of the body that have the enzymes methionine synthase and methyl malonyl CoA mutase, which convert homocysteine to 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 receptor-mediated events. First, dietary and biliary Cbl bound to gastric intrinsic factor (IF) presented apically to the ileal absorptive enterocytes is transported 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 expressed in the plasma membrane of these cells, and in polarized cells via a TC II receptor expressed in the basolateral membranes. This review updates recent work and focuses on (a) the molecular and cellular aspects of Cbl binding protein Ligands, IF and TC II, and their cell-surface receptors, IF-Cbl receptor and TC II receptor; (b) the cellular sorting pathways of internalized Cbl bound to IF and TC II in polarized epithelial cells; and (c) the absorption and transport disorders that cause Cbl deficiency.