Transcobalamin II

Transaminases Transamination Transannular peroxide Transcat process Transcobalamin II Transcortin... 

Food vitamin B 2 appears to bind to a saUvary transport protein referred to as the R-protein, R-binder, or haptocorrin. In the stomach, R-protein and the intrinsic factor competitively bind the vitamin. Release from the R-protein occurs in the small intestine by the action of pancreatic proteases, leading to specific binding to the intrinsic factor. The resultant complex is transported to the ileum where it is bound to a cell surface receptor and enters the intestinal cell. The vitamin is then freed from the intrinsic factor and bound to transcobalamin II in the enterocyte. The resulting complex enters the portal circulation. 

Transport. Transcobalamin II dehvers the absorbed vitamin 3 2 to cells and is the primary plasma vitamin B22-binding transport protein. It is found in plasma, spinal fluid, semen, and extracellular fluid. Many cells, including the bone marrow, reticulocytes, and the placenta, contain surface receptor sites for the transcobalamin II—cobalamin complex. 

Tissue Uptake and Storage. Cell surface receptors take up the transcobalamin II—cobalamin complex, which is internalized into endosomes. The complex is dissociated and the transcobalamin II released. The mechanism by which cobalamin leaves the endosome is uncertain. 

Fibroblasts Transferrin, epidermal growth factor, LDL, mannose-6-phosphate, transcobalamine II, AMPC, mannose... 

Dietary forms of vitamin B12 are converted to active forms in the body. Vitamin B12, mainly from liver, eggs and dairy products, is absorbed in terminal ileum. Intrinsic factor from parietal cells is required for absorption. Vitamin B12 is transported in the blood by transcobalamin II and stored in the liver. These stores are such that generally a patient does not become symptomatic until some years after the onset of vitamin B12 deficiency. 

The Bj 2-binding proteins of human milk have been studied in detail. The principal binding protein (R-type B12-binding protein) has a molecular mass of c. 63 kDa and contains about 35% carbohydrate. Most or all of the B12 in human milk is bound to this protein. A second protein, transcobalamin II, is present at low concentrations. 

Once absorbed, vitamin B12 is transported to the various cells of the body bound to a plasma glycoprotein, transcobalamin II. Excess vitamin Bi2 is transported to the liver for storage. Significant amounts of vitamin B,2 are excreted in the urine only when very large amounts are given parenterally, overcoming the binding capacities of the transcobalamins (50-100 Mg). 

Vitamin B12 can be absorbed when present in physiological amounts only if it is first bound to a specific protein—the so-called intrinsic factor—that tightly binds to the vitamin. The complex then passes through the jejunum to the ileum, which contains receptor sites for the vitamin B12/intrinsic factor complex. Calcium ions are required for the reaction between ileal receptors and the intrinsic factor/vitamin B12 complex. The reaction is inhibited by EDTA and reduced by a pH below 5.4. The vitamin appears to be separated from intrinsic factor at the ileal receptor sites and is then bound to another protein carrier, transcobalamin II, which transports the vitamin and permits its uptake by a number of tissues. The subject has been well reviewed by Jacob and her colleagues (Jl). Removal of 60 cm of ileum may impair vitamin B12 absorption and with the loss of 180 cm absorption is almost always affected. 

C19. Carmel, R., Tatsis, B., and Baril, L., Circulating antibody to transcobalamin II causing retention of vitamin B12 in the blood. Blood 49, 987-1000 (1977). 

D2. Daiger, S. P., Labone, M. L., Parsons, M., Wang, L., andCavalli-Sforza, L. L., Detection of genetic variation with radioactive ligands. III. Genetic polymorphism of transcobalamin II in human plasma. Am. J. Hum. Genet. 30, 202-214 (1978). 

R3. Rachmilewitz, D., Ligumsky, M., Rachmilewitz, B., Rachmilewitz, M., Tarcic, N., and Schlesinger, M., Transcobalamin II level in peripheral blood monocytes. A biochemical marker in inflammatory diseases of the bowel. Gastroenterology 78, 43-46 (1980). 

Savage, C. R., and Green, P. D., Biosynthesis of transcobalamin II by adult rat liver parenchymal cells in culture. Arch. Biochem. Biophys. 173, 691-702 (1976). 

Direct assays for vitamin B12, such as the competitive protein-binding immunoassays, detect all forms of vitamin B12 in the serum, including physiologically inactive analogues. The vitamin B12 bound to transcobalamin II (TCII) has been shown to be the physiologically... 

Figure 28-3. The absorption of vitamin B12 in humans.The sequence of transitions between protein-bound dietary vitamin B12 and circulating B12 bound to TCII. R, R proteins, haptocorrins IF, intrinsic factor TCII, transcobalamin II.

Herzlich B, Herbert V Depletion of serum holo-transcobalamin II. An early sign of negative... 

Within the ileal mucosal cell, the vitamin is released by lysosomal proteolysis of intrinsic factor, and is bound to transcobalamin II, a vitamin B12 binding protein synthesized in the enterocytes. Transcobalamin II is in vesicles destined for export from the enterocytes, and it is assumed that vitamin B12 binds to the apoprotein in these vesicles rather than in the lysosomes, because otherwise newly synthesized transcobalamin would be hydrolyzed by lysosomal proteases (Seetharam, 1999). 

Vitamin B12 enters the circulation bound to transcobalamin II there is a relatively large amount of apotranscobalamin II in the circulation, and par-enterally administered vitamin is also protein-bound. The half-life of holo-transcobalamin II in plasma is of the order of 1.5 hours, and all cells have... 

Altbougb transcobalamin II is tbe metaboUcaUy important pool of plasma vitamin B12, it accounts for only 10% to 15% of tbe total circulating vitamin. Tbe majority is bound to baptocorrin (also known as transcobalamin I). Tbe function of baptocorrin is not well understood it bas a relatively long balf-life (7 to 10 days), and does not seem to be involved in tissue uptake or intertissue transport of tbe vitamin. Altbougb genetic lack of transcobalamin 11 results in severe (and fatal) vitamin B12 deficiency, genetic lack of baptocorrin seems to bave no adverse effects. 

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