Cellular import of cobalamin (Vitamin B-12)

Recent studies have isolated and characterized human gastric intrinsic fact or (I) and transcobalamin II (TC II) genes, whose products mediate the impo rt of cobalamin (Cbl; Vitamin B-12) across cellular plasma membranes. Analy ses of cDNA and genomic clones of IF and TC II have provided some important insights into their sites of expression, structure and function. IF and TC II genes contain the same number, size and position of exons, and four of their eight intron-exon boundaries are identical. In addition, they share h igh homology in certain regions that are localized to different exons, indi cating that IF and TC II may have evolved from a common ancestral gene. Bot h IF and TC II mediate transmembrane transport of Cbl via their respective receptors that function as oligomers in the plasma membrane, If-mediated im port of Cbl is limited to the apical membranes of epithelial cells; it occu rs via a multipurpose receptor recently termed "cubilin," and the imported Cbl is usually exported out of these cells bound to endogenous TC II. On th e other hand, TC II-mediated Cbl import occurs in all cells, including epit helial cells via a specific receptor, and the Cbl imported is usually retai ned, converted to its coenzyme forms, methyl-Cbl and 5'-deoxyadenosyl-Cbl, and utilized.