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Patients treated with metformin exhibit low levels of plasma vitamin B 12 (B 12 ), and are considered at risk for developing B 12 deficiency. In this study, we investigated the effect of metformin treatment on B 12 uptake and distribution in rats.Sprague Dawley rats (n = 18) were divided into two groups and given daily subcutaneous injections with metformin or saline...
Cellular uptake of cobalamin is facilitated by a receptor-mediated endocytosis process involving transcobalamin, a plasma protein that binds cobalamin and a cell surface receptor that specifically binds transcobalamin saturated with cobalamin. Intracellular Cbl concentration is maintained by modulating the expression of the receptor, which is cell cycle associated with highest expression in actively...
Several genome-wide association studies (GWAS) have identified a strong association between serum vitamin B12 and fucosyltransferase 2 (FUT2), a gene associated with susceptibility to Helicobacter pylori infection. Hazra et al. conducted a meta-analysis of three GWAS and found three additional loci in MUT, CUBN and TCN1. Other GWAS conducted in Italy and China confirmed the association for FUT2 gene...
In our pioneering work in 1956, two binders of vitamin B 12 (B 12 ) alias cobalamin (Cbl) were identified in gastric juice, S with slow electrophoretic mobility, a 70 kD protein with intrinsic factor (IF) activity and another rapid (R), not IF active but probable digestion product. Numerous sources contained a protein immunologically identical to R (haptocorrin, Hc). Another IF-active...
Contradictory results for concentrations of vitamin B12, holotranscobalamin (holoTC), and methylmalonic acid (MMA) have been reported. We tested the hypothesis that the extracellular vitamin B12 markers are not reflecting the intracellular vitamin B12-dependent biochemical reactions in individuals with type 2 diabetes. The study included 92 patients with diabetes and 72 controls with similar age and...
Mutations in cobalamin or B 12 trafficking genes needed for cofactor assimilation and targeting lead to inborn errors of cobalamin metabolism. The gene corresponding to one of these loci, cblD, affects both the mitochondrial and cytoplasmic pathways for B 12 processing. We have demonstrated that fibroblast cell lines from patients with mutations in CblD, can dealkylate exogenously...
Since 1975 cells lines from patients with suspected inborn errors of vitamin B 12 metabolism have been referred to our laboratory because of elevations of homocysteine, methylmalonic acid, or both.Cultured fibroblasts from patients were subjected to a battery of tests: incorporation of labelled propionate and methyltetrahydrofolate into cellular macromolecules, to test the functional integrity...
In the past two decades, sensitive biochemical tests have uncovered cobalamin deficiency much more frequently than ever before. Almost all cases involve mild, biochemical changes without clinical manifestations (subclinical cobalamin deficiency; SCCD), whose health impact is unclear. Because the causes of SCCD are most often unknown, nonmalabsorptive, and seldom documented, controversy and confusion...
Intrinsic factor (IF) was first identified as a component of the gastric mucosa that reacted with an extrinsic factor, later discovered to be vitamin B12 (VB12). IF has been extensively characterized, and its cloned cDNA used to produce sufficient IF to produce high quality antibodies, and to elucidate its 3-dimensional structure bound to cobalamin (Cbl, VB12). The absorption of the IF–Cbl complex...
Vitamin B12 (cobalamin, cbl) is a cofactor of methionine synthase (MTR) in the synthesis of methionine, the precursor of the universal methyl donor S-Adenosylmethionine (SAM), which is involved in epigenomic regulatory mechanisms. We have established a neuronal cell model with stable expression of a transcobalamin–oleosin chimer and subsequent decreased cellular availability of vitamin B12, which...
The X-ray crystal structures of several important vitamin B12 binding proteins that have been solved in recent years have enhanced our current understanding in the vitamin B12 field. These structurally diverse groups of B12 binding proteins perform various important biological activities, both by transporting B12 as well as catalyzing various biological reactions. An in-depth comparative analysis...
Vitamin B12 (cobalamin) is a cobalt-containing compound synthesized by bacteria and an essential nutrient in mammals, which take it up from diet. The absorption and distribution of dietary vitamin B12 to the organism is a complex process involving several gene products including carrier proteins, plasma membrane receptors and transporters. Disturbed cellular entry, transit or egress of vitamin B12...
The classic neurological and psychiatric features associated with vitamin B 12 deficiency have been well described and are the subject of many excellent review articles. The advent of sensitive diagnostic tests, including homocysteine and methylmalonic acid assays, has revealed a surprisingly high prevalence of a more subtle ‘subclinical’ form of B 12 deficiency, particularly within...
It is known that cobalamin (Cbl) deficiency damages myelin by increasing tumor necrosis factor (TNF)-α and decreasing epidermal growth factor (EGF) levels in rat central nervous system (CNS), and affects the peripheral nervous system (PNS) morphologically and functionally. It is also known that some polyneuropathies not due to Cbl deficiency are connected with increased TNF-α levels, and that various...
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