Figure 1.

Schematic of the absorption of cobalamin by enterocytes in the distal small intestine (ileum). A, In the duodenum cobalamin is bound to intrinsic factor (IF). The cobalamin‐IF complex is then absorbed by receptor‐mediated endocytosis. This cubam receptor is localized at the brush border of the distal small intestine (ileum). The receptor complex is comprised of 2 subunits, the proteins amnionless (AMN) and cubilin (CUBN). Within the lysosomes of the enterocytes, cobalamin is separated from IF and the receptor. Bound to the transport protein transcobalamin II, cobalamin is then transported within the bloodstream to its target tissues. A small amount of circulating cobalamin is bound to transcobalamin I and thus unavailable for cellular uptake. Approximately 1% of dietary cobalamin is absorbed via passive diffusion across the intestinal mucosa. B, Various disorders can impair cobalamin metabolism