Transcobalamins I and II as natural transport proteins of vitamin B12.

Hall, C A

doi:10.1172/jci108187

Cited by 77 publications

(33 citation statements)

References 21 publications

(11 reference statements)

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“…Although the low density lipoprotein receptor appears to be under feedback regulation dependent on intracellular cholesterol content, preliminary results from our laboratory indicate that TC II receptor availability is not modulated by prior exposure to TC II or free Cbl and thus may not be involved in a similar regulatory mechanism. 2 The data with respect to the cbl C mutants show that these cells are comparable to control cells in their binding, uptake, and degradation of TC II. This evidence leads us to conclude that the underlying defect in the cbl C cells must reside at some step beyond the receptor-mediated uptake of Cbl.…”

Section: Resultsmentioning

confidence: 85%

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Binding and Uptake of Transcobalamin II by Human Fibroblasts

Youngdahl-Turner¹,

Rosenberg²,

Allen³

1978

J. Clin. Invest.

135

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A B S T R A C T We have used purified, 125I-labeled human transcobalamin II (TC II), saturated with cobalamin (Cbl), to study the uptake process for the TC II-Cbl complex by intact normal cultured human skin fibroblasts. We have also investigated the possibility that a defect in one step of this process underlies that inborn error of Cbl metabolism-designated cbl C-in which mutant cells are unable to retain Cbl intracellularly or convert it to its coenzyme forms. TC II-Cbl binding at 40C reached a plateau after 3-4 hr; 95% of the bound 1251 was releasable with trypsin. Binding of TC II-Cbl at 40C could be inhibited by human and rabbit TC II-Cbl and human TC II devoid of Cbl but not by other Cbl-binding proteins, albumin, or free Cbl. Specific binding reached saturation at =5 ng TC II/ml (0.13 nM) and could be inhibited by ethylene glycol-bis (,8-aminoethyl ether) N,N,N',N'-tetraacetic acid. At 37°C, the TC II-Cbl complex was internalized as shown by a progressive decrease in the trypsin-releasable fraction of bound 125I. After 2 h at 370C, increasing amounts of acid-soluble 1251 were found in the incubation medium indicating that the labeled TC II was being degraded. Chloroquine, an inhibitor of lysosomal proteolysis, prevented this degradation. The binding, internalization, and degradation of TC II-Cbl by cbl C cells was indistinguishable from that by control cells. Our studies provide additional support for the concepts: (a) that the TC I1-Cbl complex binds to a specific cell surface receptor through a site on the TC II; (b) that the interaction between the receptor and TC II is calcium dependent; (c) that the TC II-Cbl is internalized via

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Section: Resultsmentioning

confidence: 85%

“…It has been shown to facilitate Cbl uptake by a variety of tissues in vivo and by various cell types in vitro (1)(2)(3). Several different lines of experimentation using radioactive Cbl bound to unlabeled TC II have been employed to study the Cbl uptake process.…”

Section: Introductionmentioning

confidence: 99%

Binding and Uptake of Transcobalamin II by Human Fibroblasts

Youngdahl-Turner¹,

Rosenberg²,

Allen³

1978

J. Clin. Invest.

135

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“…Among the few known nonmalabsorptive causes of low cobalamin concentrations is hereditary absence of transcobalamin I/haptocorrin (TC I/HC) 1,2 (11-16 ), which causes low serum cobalamin concentrations because most cobalamin circulates in the blood attached to TC I/HC (17)(18)(19). Neither malabsorption nor cellular deficiency of cobalamin results from the absence of TC I/HC, which unlike transcobalamin II is not needed for cellular uptake of cobalamin.…”

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confidence: 99%

Mild Transcobalamin I (Haptocorrin) Deficiency and Low Serum Cobalamin Concentrations

Carmel

2003

Clinical Chemistry

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Background: Low cobalamin concentrations are common, but their causes are often unknown. Transcobalamin I/haptocorrin (TC I/HC) deficiency, viewed as a rare cause, has not been examined systematically in patients with unexplained low serum cobalamin. Methods: Total TC I/HC was measured by RIA in three subgroups of 367, 160, and 38 patients with different categories of low cobalamin concentrations and three comparison subgroups of 112, 281, and 119 individuals with cobalamin concentrations within the reference interval. Additional studies, including family studies, were done in selected patients found to have low TC I/HC concentrations. Results: Low TC I/HC concentrations suggestive of mild TC I/HC deficiency occurred in 54 of 367 (15%) patients with low cobalamin identified by clinical laboratories and 24 of 160 (15%) patients whose low cobalamin was unexplained after absorption and metabolic evaluation, but in only 2 of 38 patients with malabsorptive causes of low cobalamin concentrations (5%). The prevalence was only 3% (8 of 281 plasma samples) to 5% (6 of 112 sera) in patients with cobalamin concentrations within the reference interval and 3% (4 of 119) in healthy volunteers. Three patients with low cobalamin (0.6%) had severe TC I/HC deficiency with undetectable TC I/HC. Presumptive heterozygotes for severe TC I/HC deficiency in two families had the findings of mild TC I/HC deficiency; mild deficiency was also found in at least three of seven studied families of patients with mild TC I/HC deficiency. Conclusions: Mild TC I/HC deficiency is frequently associated with low cobalamin, is often familial, and its biochemical phenotype appears identical to the heterozygous state of severe TC I/HC deficiency. Severe TC I/HC deficiency also appears to be more common

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“…This is important for the tissue distribution and uptake of potential PS and has implications for the anti-angiogenic properties of PSs [80] . Porphyrins such as the heme cofactor of the glycoprotein hemoglobin are essential for gaseous transport [81] , while the glycoprotein transcobalamin provides facile transport of cofactor vitamin B 12 (cobalamin or hydroxocobalamin) into the body [82] . The detailed interactions of glycoproteins and porphyrin PSs are beyond the scope of this review, however, several documents focusing on this area have been published [83][84][85] .…”

Section: Porphyrin Bioconjugatesmentioning

confidence: 99%

Chemical Synthesis and Medicinal Applications of Glycoporphyrins

Moylan¹,

Scanlan²,

Senge

2015

CMC

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Abstract:This review presents an in-depth overview of the modification of porphyrins with bioconjugates and their applications in medicine today. Porphyrin bioconjugates ranging from nucleotides to steroids are under active scrutiny. However, carbohydrates have been at the forefront of such research in recent years and offer significant potential. This is attributed to their own selectivity to lectins on the surface of cancer cells and their influence on the amphiphilicity of the porphyrin macrocycle. These characteristics and the tendency of porphyrin photosensitizers to accumulate in tumor tissues make glycoporphyrins promising candidates for use as photosensitizers. Thus, a detailed overview of the synthesis and biological evaluation of glycoporphyrins is given with a particular focus on their applications in photodynamic therapy and their future prospects as drug candidates have been reported.

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Transcobalamins I and II as natural transport proteins of vitamin B12.

Cited by 77 publications

References 21 publications

Binding and Uptake of Transcobalamin II by Human Fibroblasts

Binding and Uptake of Transcobalamin II by Human Fibroblasts

Mild Transcobalamin I (Haptocorrin) Deficiency and Low Serum Cobalamin Concentrations

Chemical Synthesis and Medicinal Applications of Glycoporphyrins

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