Receptor for vitamin B12-IF complex is located in
Methyl-B12 is absorbed by two processes. The first is an intestinal mechanism using intrinsic factor through which 1-2 micrograms can be absorbed every few hours. The second is a diffusion process by which approximately 1% of the remainder is absorbed. The human physiology of vitamin B12 is complex, and therefore is prone to mishaps leading to vitamin B12 deficiency. Protein-bound vitamin B12 must be released from the proteins by the action of digestive proteases in both the stomach and small intestine. Gastric acid releases the vitamin from food paicles; therefore antacid and acid-blocking medications (especially proton-pump inhibitors) may inhibit absorption of B12. B12 taken in a low-solubility, non-chewable supplement pill form may bypass the mouth and stomach and not mix with gastric acids, but acids are not necessary for the absorption of free B12 not bound to protein; acid is necessary only to recover naturally-occurring vitamin B12 from foods. R-protein (also known as haptocorrin and cobalophilin) is a B12 binding protein that is produced in the salivary glands. It must wait to bind food-B12 until B12 has been freed from proteins in food by pepsin in the stomach. B12 then binds to the R-protein to avoid degradation of it in the acidic environment of the stomach. This pattern of B12 transfer to a special binding protein secreted in a previous digestive step, is repeated once more before absorption. The next binding protein for B12 is intrinsic factor (IF), a protein synthesized by gastric parietal cells that is secreted in response to histamine, gastrin and pentagastrin, as well as the presence of food. In the duodenum, proteases digest R-proteins and release their bound B12, which then binds to IF, to form a complex (IF/B12). B12 must be attached to IF for it to be efficiently absorbed, as receptors on the enterocytes in the terminal ileum of the small bowel only recognize the B12-IF complex; in addition, intrinsic factor protects the vitamin from catabolism by intestinal bacteria. Once the IF/B12 complex is recognized by specialized ileal receptors, it is transpoed into the poal circulation. The vitamin is then transferred to transcobalamin II (TC-II/B12), which serves as the plasma transpoer. Hereditary defects in production of the transcobalamins and their receptors may produce functional deficiencies in B12 and infantile megaloblastic anemia, and abnormal B12 related biochemistry, even in some cases with normal blood B12 levels. For the vitamin to serve inside cells, the TC-II/B12 complex must bind to a cell receptor, and be endocytosed. The transcobalamin-II is degraded within a lysosome, and free B12 is finally released into the cytoplasm, where it may be transformed into the proper coenzyme, by ceain cellular enzymes.Ref: Ganong&;s review of medical physiology 23rd edition Page no: 458
Ileum
Colon
Jejunum
Duodenum
G.I.T