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At least 73 records · Page 4Linked to original sources
PubMed1991

Studies on the transcobalamin receptor in hog kidney.

The binding of the cobalamin-transcobalamin complex by its solubilized receptor from hog kidney membrane was studied. The receptor bound the complex in a system containing bivalent cations, and the affinity was dependent on the NaCl concentration but not on temperature. The binding of cobalamin-transcobalamin to the receptor had an association constant of approximately 4.6 x 10(9) liter/mol and it was saturable and highly specific as competition by other proteins was not observed. The receptor had higher affinity for the cobalamin-transcobalamin complex (holo-TC) than for transcobalamin (apo-TC). Basic amino compounds known to interfere with tubular reabsorption of proteins did not inhibit the binding. Studies on subcellular fractions supported the view that the receptor was located on the brush border membrane of the kidney.

Animals↗
PubMed1976

A familial abnormality of circulating vitamin B12 binding proteins: occurrence in a family of high serum concentrations of transcobalamin II.

A family is described in which two members (a father and a daughter), both with quiescent ulcerative colitis, had abnormally high serum concentrations of a vitamin B12 binding protein. This protein had the molecular weight of transcobalamin II on gel filtration, and behaved like transcobalamin II with respect to its elution from DE-23 cellulose, its inhibition at acid pH, its absorption by uncoated charcoal, its binding by anti-TC II antibodies, and its ability to transfer vitamin B12 to transformed lymphocytes. Its plasma clearance and tissue distribution when injected into rabbits was indistinguishable from that of transcobalamin II from normal subjects. It migrated on electrophoresis in the beta, gamma region. This is the first case report of related subjects in whom high serum concentrations of transcobalamin II have been observed.

Blood Proteins↗
PubMed1986

Increased levels of apo-transcobalamins I and II in amniotic fluid from pregnant women with previous neural tube defect offspring.

In an attempt to identify biochemical components of the genetic predisposition to neural tube defects (NTDs), levels of folate, cobalamin, apo-transcobalamins I and II and alpha-fetoprotein were studied in midtrimester amniotic fluid from 24 pregnant women who had previously had a child with NTD. The control group consisted of 76 mothers, subjected to amniocentesis for reasons other than risk of NTD in offspring. Only pregnancies with normal outcome were included. No differences were found between groups for levels of folate, cobalamin or alpha-fetoprotein. Folate intake or metabolism did not appear to differ between groups. In contrast, the level of apo-transcobalamin I was doubled and the level of apo-transcobalamin II tripled in amniotic fluid from women who had had a child with NTD compared with the control group. Since the variation in apo-transcobalamin II in adults is to a high degree genetically determined, the present results may suggest that the genetic predisposition to NTD is associated with variation in this protein. Further studies are needed to substantiate or reject this possibility.

Adult↗
PubMed1975

Role of transcobalamins I, II, and III in the transfer of vitamin B12 to human bone marrow cells in vitro.

A study of the uptake of transcobalamin-bound 57Co-cyanocobalamin by suspensions of human bone marrow cells has indicated that these cells can take up vitamin B12 from all 3 transcobalamins (I, II, and III). Similar transport processes were involved in the uptake from the 3 transcobalamins; uptake was dependent on the presence of calcium ions, cellular respiration and free sulphydryl groups. These results suggest that contrary to current belief, all 3 transcobalamins play a role in the transfer of vitamin B12 to tissue cells.

Biological Transport↗
PubMed1986

Uptake of transcobalamin II-bound cobalamin by isolated rat kidney tubule cells.

The uptake and intracellular processing of transcobalamin II-bound cobalamin by isolated rat kidney tubule cells were studied. The cells absorbed the complex in a temperature-and calcium-dependent process, which could be inhibited by monensin, an inhibitor of endocytosis. Cells, loaded with a mixture of 125I- and 57Co-labelled transcobalamin II-vitamin B12, released 125I-labelled protein-degradation products, while keeping the 57Co-labelled vitamin. Protein degradation was inhibited by chloroquine and monensin, which is further evidence for a process of endocytosis, followed by intralysosomal hydrolysis of the transport protein. Transcobalamin II-vitamin B12 uptake was not fully saturable and other proteins, for example, haemoglobin, inhibited the uptake in a concentration-dependent way. Apparently the uptake proceeds through relatively unspecific protein-binding sites, probably involved in the reabsorption of filtrated proteins, although the affinity for transcobalamin II seems relatively high. Consequently, elevated urinary excretion of cobalamin is expected in patients with overflow proteinuria, and was indeed found in a patient with paroxysmal nocturnal haemoglobinuria.

Animals↗
PubMed1993

Transcobalamin II mediated delivery of albumin-bound hydroxocobalamin to human liver cells.

We show that hydroxocobalamin bound to human serum albumin can dissociate and bind to transcobalamin II present in serum. Human liver cells in culture exposed to hydroxocobalamin bound to albumin incorporated less of the vitamin than when similar amounts of unbound hydroxocobalamin or cyanocobalamin were present. In the presence of transcobalamin II, a 4.5-fold increase in cellular uptake occurred, but this amount was less than when hydroxocobalamin or cyanocobalamin were added to transcobalamin II. These results indicate that albumin, by binding hydroxocobalamin, can alter the dynamics of binding to transcobalamin II and the subsequent cellular incorporation of this form of the vitamin.

Humans↗
PubMed1975

Turnover in humans of iodine- and cobalamin-labeled transcobalamin I and of iodine-labeled albumin.

Purified transcobalamin I labeled with radioactive iodine and cobalamin was used for turnover studies in 17 humans. Mean fractional catabolic rate was 0.15 d-1 and mean distribution ratio was 0.57. No difference was observed between the turnover in a control group and in patients with vitiligo or pernicious anemia. The plasma curves of the iodine and the cobalamin label were identical, indicating that cobalamin was liberated from transcobalamin I only when this protein was degraded. It was further concluded that transcobalamin I was of minor importance for the transport of cobalamin from the gut to the tissues. The turnover of transcobalamin I was correlated to the turnover of albumin in 9 patients studied with both proteins.

Adult↗
PubMed1980

Adherence of L1210 murine leukemia cells to sephacryl-aminopropylcobalamin beads treated with transcobalamin-II.

Sephacryl beads containing an immobilized aminopropylcobalamin-transcobalamin-II complex serve as foci for the adherence of L1210 murine leukemia cells. Bead-cell interaction does not occur when (A) nonderivatized beads are used; (B) transcobalamin-II is omitted or presaturated with cyanocobalamin in the preparation of the bead complex; (C) intrinsic factor replaces transcobalamin-II; and (D) the complex is removed from beads by photolysis. These observations suggest that adherence results from the ability of transcobalamin-II to form a bridge between immobilized cobalamin on the bead and receptors in the plasma membrane of the cell.

Acrylic Resins↗
PubMed1983

Clinical significance of serum transcobalamins in protein-energy malnutrition.

The serum concentrations of Unsaturated Vitamin B(12) binding (UBBC) capacity and the three individual transcobalamins were measured in 34 malnourished children aged 9 months-5 y. Levels of serum vitamin B12, aspartate aminotransferase, alanine aminotransferase, albumin and total proteins were also estimated. The serum UBBC, Transcobalamin I (TC I), Transcobalamin III (TC III), vitamin B12 and the enzyme activities were significantly higher in the kwashiorkor children when compared with both the marasmic and control children. There was also a marked reduction of serum Transcobalamin II (TC II), albumin and total proteins in the kwashiorkor children. In contrast with kwashiorkor, there was a slight increase of serum TC II in the marasmic children. Their serum UBBC, TC I, TC III and B12 were also raised but not as high as in kwashiorkor. These results are discussed in the light of the hepatic dysfunction in kwashiorkor affecting the production of TC II in the liver, while the elevated serum B12 in Protein-energy malnutrition (PEM) may be due to both hepatic damage and intensified release of TC I as a result of infection.

Journal Article↗
PubMed1979

Purification of human transcobalamin II-cyanocobalamin by affinity chromatography using thermolabile immobilization of cyanocobalamin.

Transcobalamin II-cyanocobalamin was isolated from Cohn fraction III of pooled human plasma by affinity chromatography on cyanocobalamin-Sepharose and some conventional separation methods. The affinity ligand cyanocobalamin was coupled to AH-Sepharose by a thermolabile linkage. The unsaturated binding protein was absorbed at 4 degrees C and eluted from the column at 37 degrees C as transcobalamin II-cyanocobalamin complex. The final preparation had a specific cyanocobalamin-binding capacity of 0.98 mol cyanocobalamin/mol transcobalamin II, the yield was 55% and the purification index amounted to 1.1 . 10(6). In dodecyl sulphate polyacrylamide gel electrophoresis one major protein band was observed at a molecular weight of 37 000 and a faint band at a molecular weight of 29 000. In polyacrylamide gel isolectric focusing the pure preparation turned out to be heterogeneous with isoelectric points ranging from pH 6.2 to 6.8, possibly by the occurrence of isoproteins.

Blood Proteins↗
PubMed1989

Uptake of transcobalamin II-bound cobalamin by HL-60 cells: effects of differentiation induction.

Binding and uptake of transcobalamin II-bound cobalamin by HL-60 promyelocytic leukemia cells proceed through receptor-mediated endocytosis. The affinity constant of the receptor for transcobalamin II-cobalamin was found to be 6.1 liter/nmol and the maximal rate of uptake 12 pmol/10(9) cells/h. This uptake is mediated by about 3000 receptor sites per cell. Evidence is presented that the receptor recirculates from the cell surface to the lysosomes and vice versa. Upon differentiation induction of the cells by either DMSO in granulocytic direction or by 1,25-dihydroxy-vitamin D3 in monocytic direction a rapid decline in cellular uptake and cell surface binding of the protein-bound vitamin ensues. In particular the internalization of the complex decreases faster than all other observed signs of the ongoing differentiation process, such as reduction in the OKT9-reactive transferrin receptor, increase in lineage-specific surface markers, and decrease in [3H]thymidine incorporation and actual cell proliferation. The transcobalamin II receptor on the cell surface appears to be a proliferation-associated membrane component in human leukemic cells.

Calcitriol↗
PubMed1992

Transcobalamin II--cobalamin binding sites are present on rabbit germ cells.

Specific binding sites for rabbit transcobalamin II have been found on isolated adult rabbit germ cells. Scatchard analysis revealed a single class of binding sites for [57Co]cyanocobalamin-transcobalamin II with an association constant (Ka) of 1.3 x 10(10) M-1 and 700 sites per cell. Binding was reversible, saturable and calcium dependent. Electron microscope radioautography following incubation with iodinated transcobalamin II at 4 degrees C led to a detectable labeling mainly restricted to the plasma membrane.

Animals↗
PubMed1988

Separation of transcobalamin II isoproteins by means of chromatofocusing.

Transcobalamin II, the principal cobalamin-binding protein in human plasma, expresses a genetic polymorphism. Four more or less common alleles, denoted by X, S, M and F, have been defined earlier by means of gel electrophoretic techniques followed by autoradiography. This technique is less suitable for the analysis of individual samples and requires long exposure times. This paper describes the analysis of transcobalamin II phenotypes by means of fast protein liquid chromatofocusing. This technique has the advantage that the results of the analysis of several samples can be obtained within a day, and it also seems applicable to the preparative separation of transcobalamin II isoproteins. The sequence of elution of the isoproteins was in complete accordance with the banding pattern obtained by electrophoretic separation. The characteristic doublet bands found with polyacrylamide gel electrophoresis were less obvious in the chromatofocusing elution pattern.

Chromatography, Liquid↗
PubMed1979

Distribution of endogenous cobalamin between the transcobalamins in various mammals.

1. Plasma samples from ten mammals were chromatographed on Sephadex G-200 columns and the total cobalamin content of each fraction was determined. 2. Unlike the situation in man, the bulk of the endogenous plasma cobalamin was found attached to a transcobalamin II-like protein in all ten animals. Transcobalamin 0 carried between 3 and 20% and this proportion appeared to be inversely related to the plasma total cobalamin. No endogenous cobalamin peak corresponding to transcobalamin I was detected in any species, though in the rabbit 5.3% of the plasma total cobalamin was attached to a protein of apparent molecular weight 176 000.

Animals↗
PubMed1996

In vitro and in vivo inactivation of transcobalamin II receptor by its antiserum.

Rabbits injected with pure human placental transcobalamin II-receptor (TC II-R) failed to thrive with no apparent tissue or organ damage, but a 2-fold elevation of the metabolites, homocysteine, methylmalonic acid, and the ligand, transcobalamin II, in their plasma. Exogenously added transcobalamin II-[57Co]cyanocobalamin bound very poorly (2-5%) to the affected rabbit liver, kidney, and intestinal total or intestinal basolateral membrane extracts relative to the binding by membrane extracts from normal rabbit tissues. The activity was restored to normal values following a wash of affected rabbit tissue membranes with pH 3 buffer containing 200 mM potassium thiocyanate. Immunoblot analysis of normal and affected rabbit kidney and liver total membranes revealed similar amounts of 124-kDa TC II-R dimer protein. The neutralized and dialyzed extract from the affected rabbit membranes inhibited the binding of the ligand to pure TC II-R and the harvested affected rabbit serum inhibited the uptake of TC II-[57Co]cobalamin (Cbl) from the basolateral side of human intestinal epithelial (Caco-2) cells and decreased the utilization of [57Co]Cbl as coenzymes by the Cbl-dependent enzymes. The loss of exogenously added ligand binding or the binding of 125I-protein A occurred with the intestinal basolateral, but not the apical membranes. Based on these results, we suggest that circulatory antibodies to TC II-R cause its in vivo functional inactivation, suppress Cbl uptake by multiple tissues, and thus cause severe Cbl deficiency and the noted failure to thrive.

Animals↗
PubMed2005

Transcobalamin 776C->G polymorphism negatively affects vitamin B-12 metabolism.

BACKGROUND: A common genetic polymorphism [transcobalamin (TC) 776C-->G] may affect the function of transcobalamin, the protein required for vitamin B-12 cellular uptake and metabolism. Remethylation of homocysteine is dependent on the production of 5-methyltetrahydrofolate and adequate vitamin B-12 for the methionine synthase reaction. OBJECTIVES: The objectives were to assess the influence of the TC 776C--> G polymorphism on concentrations of the transcobalamin-vitamin B-12 complex (holo-TC) and to determine the combined effects of the TC 776C-->G and methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphisms and vitamin B-12 status on homocysteine concentrations. DESIGN: Healthy, nonpregnant women (n = 359; aged 20-30 y) were screened to determine plasma vitamin B-12, serum holo-TC, and plasma homocysteine concentrations and TC 776C-->G and MTHFR 677C-->T genotypes. RESULTS: The serum holo-TC concentration for women with the variant TC 776 GG genotype was significantly different (P = 0.0213) from that for subjects with the CC genotype (74 +/- 37 and 87 +/- 33 pmol/L, respectively). An inverse relation was observed between plasma homocysteine concentrations and both serum holo-TC (P </= 0.0001) and plasma vitamin B-12 (P </= 0.0001) concentrations, regardless of genotype. CONCLUSIONS: These data suggest that the TC 776C-->G polymorphism negatively affects the serum holo-TC concentration and provide additional evidence that vitamin B-12 status modulates the homocysteine concentration in this population.

Adult↗
PubMed1991

Effect of the cobalt-N coordination on the cobamide recognition by the human vitamin B12 binding proteins intrinsic factor, transcobalamin and haptocorrin.

The binding of several corrinoids to the binding site of human intrinsic factor, transcobalamin or haptocorrin was investigated, p-Cresolyl cobamide and 2-amino-vitamin B12 are complete corrinoids, whose nucleotide at the lower face of the corrin ring is not coordinated to the cobalt. These corrinoids were greater than or equal to 10(3) times less efficiently recognized by intrinsic factor or transcobalamin than vitamin B12, which contains a Co-coordinated nucleotide. Pseudovitamin B12, with a weak Co-N coordination bond, revealed only moderate affinity to intrinsic factor. From these findings it is concluded that the cobamide binding to intrinsic factor and transcobalamin is strongly affected by the Co-N coordination bonds of their lower cobalt nucleotide ligands. We suggest that the Co-N coordination bond positions the nucleotide at a critical distance to the corrin ring, which is recognized by the binding proteins. Human haptocorrin, however, disclosed to distinctive selectivity regarding the different corrinoid structures. The protein bound all corrinoids with similar efficiency, independent of the strength of their Co-N coordinations, or the structures of their lower Co alpha ligands. Hence, the corrin ring, rather than a structural feature induced by the Co-N coordination, has to be considered responsible for the corrinoid binding to haptocorrin.

Binding Sites↗
PubMed1982

Serum transcobalamins in healthy Nigerian children.

The unsaturated vitamin B12-binding capacity (UB12BC) and the three transcobalamins (TC I, TC II, TC III) have been studied in the serum of normal healthy Nigerian children. The serum UB12BC level was very high in the children: TC I accounted for 39.5% of UB12BC, TC II accounted for 49.5% and TC III accounted for 11%. The results are discussed in the light of the variations in the distribution of transcobalamins in children from what has been previously reported among the African adults. The high percentage of TC I in the children is discussed in the light of a possible immunological role of this transcobalamin. There was an inverse relationship between TC I and TC II levels. A sex difference in UB12BC and TC I levels was observed. The girls had higher UB12BC and this was due to higher TC I, but the advantage of this is not clear.

Black People↗