Transcobalamin serum

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). 

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... 

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

The measurement of holotranscobalamin II is potentially useftil as a specific marker of biologically available vitamin Bi2, because only cobalamin bound to Tell is specifically available for uptake by aU cells. Other methods have been described for the measurement of holotranscobalamin in serum, one using an immobilized monoclonal antibody to human transcobalamin, followed by measurement of released cobalamin by CPB, This method is currently available as a commercial kit. The other method uses magnetic beads coated with cobalamin to precipitate apotranscobalamin followed by measurement of the holotranscobalamin in the supernatant by ELISA. Though these methods are claimed to be precise and simple to perform, there remains doubt over the interpretation of the measured concentrations, and over their sensitivity and specificity in the diagnosis of vitamin B deficiency. ... 

Irjala K, Isoaho R et al. RIA for serum holo-transcobalamin method evaluation in the clinical laboratory and reference interval. Clin Chem 2003 49 455-62. 

The serum cobalophilins, transcobalamin I and III (TCI and TCIII), are immunologically identical and may differ only in their carbohydrate content. TCI moves as an a ] -globulin in standard serum protein electrophoresis, while TCIII moves as an a2-globuIin owing to its lower sialic acid content. Plasma TCIII... 

After the stomach s acidic environment facilitates the breakdown of vitamin B12 bound to food, the vitamin B12 binds to the intrinsic factor released by the stomach s parietal cells. The secretion of intrinsic factor generally corresponds to the release of hydrochloric acid and serves as a cell-directed carrier protein similar to transferrin for iron. This complex, resistant to degradation, forms in the duodenum and allows for subsequent absorption of vitamin B12 in the terminal ileum. The cobalamin-intrinsic factor complex is taken up into the ileal mucosal cell, the intrinsic factor is discarded, and the cobalamin is transferred to transcobalamin It, which serves as a transport protein. This complex is secreted into the circulation and is taken up by the fiver, bone marrow, and other cells. Transcobalamin 11 has a short half-fife of 1 hour and is rapidly cleared from the blood. Consequently, most circulating cobalamin is bound to serum haptocorrins (formerly transcobalamin I and transcobalamin IB) whose function is unknown. However, it should be noted that an alternate pathway for vitamin B12 absorption independent of intrinsic factor or an intact ter-... 

Dietary cobalamin is absorbed from animal food sources by a multistage process shown in Figure 42-2. Cobalamin absorption requires the presence of a protein (the intrinsic factor, IF) secreted from the parietal cells of the stomach to bind cobalamin and aid in its absorption in the ileum. The protein is released into the ileum while the cobalamin is transported to the blood stream where it binds specialized serum proteins, the transcobalamins (TC), which transport it to other tissues such as liver where cobalamin can be stored (usually several milligrams are present in liver). In the absence of the intrinsic factor... 

The total amount of cobalamin present in serum is in the magnitude of 400pmol/L. Circulating cobalamins are bound to two proteins. Transcobala-min (TC) carries approximately 20% of the cobalamins in serum and the protein haptocorrin (HC) carries the remaining 80% (Nexo and Andersen 1977). In contrast, the amount of unsaturated (apo) transcobalamin is high compared with that of haptocorrin (Figure 26.1). 

Serum cobalamin consists of picomolar amounts of several forms of the vitamin bound to transcobalamin or haptocorrin. 

Measurement of serum cobalamin includes release of cobalamin from its binding proteins transcobalamin and haptocorrin, conversion of the various forms of cobalamin into one form of the vitamin, and quantification employing microbiological or protein binding assays. 

Cobalamin analogues Cobalamin analogues are cobalamin-related molecules not able to act as coenzymes for the cobalamin dependent human enzymes. In serum, both cobalamin and cobalamin analogues are present. The protein transcobalamin can only bind active forms of cobalamin, whereas the protein haptocorrin can bind both cobalamins and analogues. 

Holotranscobalamin (holoTC) HoloTC is cobalamin bound to transcobalamin and this is the available cobalamin for the cells. There is now a debate as to whether measurement of holoTC is a better marker for identifying individuals with cobalamin deficiency than total serum cobalamin. 

Loikas, S., Lopponen, M., Suominen, P., Moller, J., Irjala, K., Isoaho, R., Kivela, S.L., Koskinen, P., and Pelliniemi, T.T., 2003. RIA for serum holo-transcobalamin method evaluation in the clinical laboratory and reference interval. Clinical Chemistry. 49 455-462. 

Chen, X., Remacha, A.F., Sarda, M.P., and Carmel, R., 2005. Influence of cobalamin deficiency compared with that of cobalamin absorption on serum holo-transcobalamin II. The American Journal of Clinical Nutrition. 81 110-114. 

Ulleland, M., Eilertsen, I., Quadros, E.V., Rothenberg, S.P., Fedosov, S.N., Sun-drehagen, E., and Orning, L., 2002. Direct assay for cobalamin bound to transcobalamin (holo-transcobalamin) in serum. Clinical Chemistry. 48 526-532. 

Once in the blood, hydroxocobalamin, the precursor vitamin, is transported by two different serum globulins, transcobalamins (TC) I and II. Trans-cobalamin II is a /3-globulin and is concerned with the transport of newly absorbed vitamin while transcobalamin I, an a-globulin, carries the majority of the vitamin found in plasma and is also concerned with storage (Rosenberg, 1978). Hydroxocobalamin is transported into the cell bound to transcobalamin II via a specific cell-surface calcium-dependent receptor-mediated endocytic... 

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