Transcobalamins

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. 

Other plasma vitamin B 2 proteins, transcobalamines I and III, appear to have primarily a storage function and only a lesser role in transport. 

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... 

Enterocytes Maternal IgG, dimeric IgA, transcobalamine-Bi2/ intrinsic factor... 

Mammalian intestinal absorption requires the presence of two receptors and two transporters, which is itself a unique feature. Specific transporters such as intrinsic factor, transcobalamin, and haptocorrin have been characterized,1113 as well as a number of receptors for passage across cell membranes. A number of biochemical studies on cell uptake1114 and receptors1115,1116 of cobala-mins have been reported. Genetic disorders that impair the synthesis, transport, or transmembrane passage of cobalamins and their consequences have been reviewed.1117,1118... 

Vitamin B12 (cyanocobalamin) is produced by bacteria B12 generated in the colon, however, is unavailable for absorption (see below). liver, meat, fish, and milk products are rich sources of the vitamin. The minimal requirement is about 1 pg/d. Enteral absorption of vitamin B 2 requires so-called intrinsic factor from parietal cells of the stomach. The complex formed with this glycoprotein undergoes endocytosis in the ileum. Bound to its transport protein, transcobalamin, vitamin B12 is destined for storage in the liver or uptake into tissues. 

P-Globulins Lipoprotein (LDL) Transferrin Fibrinogen Sex hormonebinding globulin Transcobalamin C-reactive protein... 

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. 

Once absorbed, vitamin B12 is transported to the various cells of the body bound to a family of specialized glycoproteins, transcobalamin I, II, and III. Excess vitamin B12 is transported to the liver for storage. 

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. 

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. 

Approximately 90% of the unsaturated vitamin B12 binding capacity of sonicates of peripheral blood granulocytes appears to be TC III, while the remainder is TC I (S6). Granulocytes have not been found to contain TC II. Studies on the delivery of vitamin B12 to human lymphocytes by TC I, TC II, and TC III have shown that in lymphocyte cultures the uptake of [57Co]B12 from its complex with TC II was substantially higher than from complexes with other binders. It was concluded from these experiments that TC III, like TC I, did not promote uptake of vitamin B12 by human hemopoietic cells and that these two transcobalamins appear to be storage proteins (M2). 

B2. Burger, R. L., Mehlman, C. S., and Allen, R. H., Human plasma R-type vitamin B12 binding proteins. I. Isolation and characterisation of transcobalamin I, transcobalamin III and the normal granulocyte vitamin B12 binding protein. J. Biol. Chem. 250, 7700-7706 (1975). 

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). 

F3. Frater-Schr der, M., Hitzig, W. H., and Butler, R. Studies on transcobalamin (TC). 1. Detection of TCII isoproteins in human serum. Blood 53, 193-203 (1979). 

H6. Hippe, E., Haber, E., and Olsen, H., Nature of vitamin B12 binding. II. Steric orientation of vitamin B12 on binding and number of combining sites of human intrinsic factor and the transcobalamins. Biochim. Biophys. Acta 243, 75-82 (1971). 

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