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Medicina 2019High serum levels of vitamin B12 or cobalamin, also called hypervitaminemia B12, is a frequently underestimated biological abnormality. According to the literature, some... (Review)
Review
High serum levels of vitamin B12 or cobalamin, also called hypervitaminemia B12, is a frequently underestimated biological abnormality. According to the literature, some of the entities related to this finding are solid neoplasia (primary or metastatic) and acute or chronic hematological diseases. Other causes include liver disorders, monoclonal gammapathy of undetermined significance, renal failure and, less frequently, excess of vitamin B12 intake, inflammatory or autoimmune diseases, and transient hematological disorders (neutrophilia and secondary eosinophilia). This article reports on causes of hypervitaminosis B12, our experience and a review of the literature.
Topics: Acute Kidney Injury; Hematologic Diseases; Humans; Liver Diseases; Neoplasms; Nutrition Disorders; Vitamin B 12
PubMed: 31671389
DOI: No ID Found -
Frontiers in Molecular Biosciences 2016Vitamin B12 (cobalamin, Cbl, B12) is an indispensable water-soluble micronutrient that serves as a coenzyme for cytosolic methionine synthase (MS) and mitochondrial... (Review)
Review
Vitamin B12 (cobalamin, Cbl, B12) is an indispensable water-soluble micronutrient that serves as a coenzyme for cytosolic methionine synthase (MS) and mitochondrial methylmalonyl-CoA mutase (MCM). Deficiency of Cbl, whether nutritional or due to inborn errors of Cbl metabolism, inactivate MS and MCM leading to the accumulation of homocysteine (Hcy) and methylmalonic acid (MMA), respectively. In conjunction with total B12 and its bioactive protein-bound form, holo-transcobalamin (holo-TC), Hcy, and MMA are the preferred serum biomarkers utilized to determine B12 status. Clinically, vitamin B12 deficiency leads to neurological deterioration and megaloblastic anemia, and, if left untreated, to death. Subclinical vitamin B12 deficiency (usually defined as a total serum B12 of <200 pmol/L) presents asymptomatically or with rather subtle generic symptoms that oftentimes are mistakenly ascribed to unrelated disorders. Numerous studies have now established that serum vitamin B12 has limited diagnostic value as a stand-alone marker. Low serum levels of vitamin B12 not always represent deficiency, and likewise, severe functional deficiency of the micronutrient has been documented in the presence of normal and even high levels of serum vitamin B12. This review discusses the usefulness and limitations of current biomarkers of B12 status in newborn screening, infant and adult diagnostics, the algorithms utilized to diagnose B12 deficiency and unusual findings of vitamin B12 status in various human disorders.
PubMed: 27446930
DOI: 10.3389/fmolb.2016.00027 -
Nutrients Nov 2019Vegans are at an increased risk for certain micronutrient deficiencies, foremost of vitamin B. Little is known about the short-term effects of dietary change to... (Randomized Controlled Trial)
Randomized Controlled Trial
Vegans are at an increased risk for certain micronutrient deficiencies, foremost of vitamin B. Little is known about the short-term effects of dietary change to plant-based nutrition on vitamin B metabolism. Systemic biomarkers of vitamin B status, namely, serum vitamin B and holotranscobalamin, may respond quickly to a reduced intake of vitamin B. To test this hypothesis, 53 healthy omnivore subjects were randomized to a controlled unsupplemented vegan diet (VD, = 26) or meat-rich diet (MD, = 27) for 4 weeks. Vitamin B status was examined by measurement of serum vitamin B, holotranscobalamin (holo-TC), methylmalonic acid (MMA) and total plasma homocysteine (tHcy). Holo-TC decreased significantly in the VD compared to the MD group after four weeks of intervention, whereas metabolites MMA and tHcy were unaffected. Body weight remained stable in both groups. VD intervention led to a significant reduction of cholesterol intake, and adequate profiles of nutrient and micronutrient status. Lower intake of vitamin B was observed in VD, which was mirrored by a lower concentration of serum vitamin B and reduced holo-TC after 4 weeks. Plasma holo-TC may be a fast-responding biomarker to monitor adequate supply of vitamin B in plant-based individuals.
Topics: Adult; Biomarkers; Cardiovascular Diseases; Cholesterol; Diet, Vegan; Fatty Acids; Female; Healthy Volunteers; Homocysteine; Humans; Inflammation; Male; Methylmalonic Acid; Micronutrients; Nutritional Status; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 31752105
DOI: 10.3390/nu11112815 -
American Journal of Human Genetics Apr 2009The B vitamins are components of one-carbon metabolism (OCM) that contribute to DNA synthesis and methylation. Homocysteine, a by-product of OCM, has been associated...
The B vitamins are components of one-carbon metabolism (OCM) that contribute to DNA synthesis and methylation. Homocysteine, a by-product of OCM, has been associated with coronary heart disease, stroke and neurological disease. To investigate genetic factors that affect circulating vitamin B6, vitamin B12, folate and homocysteine, a genome-wide association analysis was conducted in the InCHIANTI (N = 1175), SardiNIA (N = 1115), and BLSA (N = 640) studies. The top loci were replicated in an independent sample of 687 participants in the Progetto Nutrizione study. Polymorphisms in the ALPL gene (rs4654748, p = 8.30 x 10(-18)) were associated with vitamin B6 and FUT2 (rs602662, [corrected] p = 2.83 x 10(-20)) with vitamin B12 serum levels. The association of MTHFR, a gene consistently associated with homocysteine, was confirmed in this meta-analysis. The ALPL gene likely influences the catabolism of vitamin B6 while FUT2 interferes with absorption of vitamin B12. These findings highlight mechanisms that affect vitamin B6, vitamin B12 and homocysteine serum levels.
Topics: Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Female; Folic Acid; Fucosyltransferases; Genome-Wide Association Study; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Neoplasm Proteins; Polymorphism, Single Nucleotide; Receptors, Cell Surface; Transcobalamins; Vitamin B 12; Vitamin B 6; Galactoside 2-alpha-L-fucosyltransferase
PubMed: 19303062
DOI: 10.1016/j.ajhg.2009.02.011 -
Journal of Inherited Metabolic Disease May 2023Vitamin B (cobalamin, Cbl) is required as a cofactor by two human enzymes, 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) and methylmalonyl-CoA mutase... (Review)
Review
Vitamin B (cobalamin, Cbl) is required as a cofactor by two human enzymes, 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) and methylmalonyl-CoA mutase (MMUT). Within the body, a vast array of transporters, enzymes and chaperones are required for the generation and delivery of these cofactor forms. How they perform these functions is dictated by the structure and interactions of the proteins involved, the molecular bases of which are only now being elucidated. In this review, we highlight recent insights into human Cbl metabolism and address open questions in the field by employing a protein structure and interactome based perspective. We discuss how three very similar proteins-haptocorrin, intrinsic factor and transcobalamin-exploit slight structural differences and unique ligand receptor interactions to effect selective Cbl absorption and internalisation. We describe recent advances in the understanding of how endocytosed Cbl is transported across the lysosomal membrane and the implications of the recently solved ABCD4 structure. We detail how MMACHC and MMADHC cooperate to modify and target cytosolic Cbl to the client enzymes MTR and MMUT using ingenious modifications to an ancient nitroreductase fold, and how MTR and MMUT link with their accessory enzymes to sustainably harness the supernucleophilic potential of Cbl. Finally, we provide an outlook on how future studies may combine structural and interactome based approaches and incorporate knowledge of post-translational modifications to bring further insights.
Topics: Humans; Vitamin B 12; Methylmalonyl-CoA Mutase; Biological Transport; Molecular Chaperones; ATP-Binding Cassette Transporters; Oxidoreductases
PubMed: 36680553
DOI: 10.1002/jimd.12593 -
Animals : An Open Access Journal From... Apr 2023Cobalamin is a water-soluble molecule that has an important role in cellular metabolism, especially in DNA synthesis, methylation, and mitochondrial metabolism.... (Review)
Review
Cobalamin is a water-soluble molecule that has an important role in cellular metabolism, especially in DNA synthesis, methylation, and mitochondrial metabolism. Cobalamin is bound by intrinsic factor (IF) and absorbed in the ileal tract. The IF in cats is synthesized exclusively by pancreatic tissue. About 75% of the total plasma cobalamin in cats is associated with transcobalamin II, while in this species, transcobalamin I is not present. In cats, the half-life of cobalamin is 11-14 days. Diagnostic biomarkers for B12 status in cats include decreased levels of circulating total cobalamin and increased levels of methylmalonic acid. The reference interval for serum cobalamin concentrations in cats is 290-1500 ng/L, and for the serum methylmalonic acid concentration, it is 139-897 nmol/L. Therapy for hypocobalaminemia mainly depends on the underlying disease. In some cases, subcutaneous or intramuscular injection of 250 μg/cat is empirically administered. In recent years, it has been demonstrated that oral cobalamin supplementation can also be used successfully in dogs and cats as a less invasive alternative to parental administration. This review describes the current knowledge regarding B12 requirements and highlights improvements in diagnostic methods as well as the role of hypocobalaminemia in its associated diseases.
PubMed: 37174511
DOI: 10.3390/ani13091474 -
JDS Communications May 2021In human nutrition, bovine milk is an essential source of bioavailable vitamin B and B-binding proteins, including transcobalamin. In this study, we estimated genetic...
In human nutrition, bovine milk is an essential source of bioavailable vitamin B and B-binding proteins, including transcobalamin. In this study, we estimated genetic parameters for milk content of vitamin B and transcobalamin using milk samples from 341 and 663 Danish Holstein cows, respectively. Additionally, we conducted whole-genome association analysis to identify SNP and genes associated with vitamin B and transcobalamin. Our results indicated moderate to high heritability for vitamin B (0.37 ± 0.18) and transcobalamin (0.61 ± 0.13) content in the Danish Holstein. With a significance threshold of -log -value > 5.87, significant associations were detected between SNP in autosome (BTA)17 and the log-transformed transcobalamin content of milk; no significant association was detected for vitamin B. The significant region in BTA17 was imputed to full sequence for further fine mapping, and the SNP with the most significant associations to transcobalamin were assigned to the transcobalamin 2 () gene.
PubMed: 36339496
DOI: 10.3168/jdsc.2020-0048 -
Biochimie Jul 2016Cobalamin/Vitamin B12 (Cbl) is an essential vitamin, supplied mainly as hydroxocobalamin (OHCbl) by animal products, including cows' milk. Cyanocobalamin (CNCbl) is the...
INTRODUCTION
Cobalamin/Vitamin B12 (Cbl) is an essential vitamin, supplied mainly as hydroxocobalamin (OHCbl) by animal products, including cows' milk. Cyanocobalamin (CNCbl) is the usual form in vitamin pills. The aim was to explore absorption and tissue accumulation of two Cbl forms, administered alone or bound to milk protein.
MATERIALS AND METHODS
We synthesized labeled OH[(57)Co]Cbl from commercially available CN[(57)Co]Cbl. Recombinant bovine transcobalamin (rbTC) was produced in yeast and skimmed milk obtained off the shelf. Male Wistar rats (250-300 g) received labeled Cbl by gastric gavage. First, we administered CN[(57)Co]Cbl, free or rbTC-bound (n = 15 in each group). Rats were sacrificed after two, 24, and 48 h. In the following studies, rats were sacrificed after 24 h. We compared absorption of free or rbTC-bound CN[(57)Co]Cbl added to cows' milk and analogous absorption of OH[(57)Co]Cbl, free or rbTC-bound, to absorption of free CN[(57)Co]Cbl, (n = 10 in each group). Blood, tissues, 24-h urine and feces were collected. Labeled Cbl was measured using a gamma counter. Results are expressed as percentage of administered dose.
RESULTS
Absorptions of CNCbl and OHCbl were neither influenced by rbTC-binding nor administration in milk. Absorption increased in the first 24 h with no further tissue accumulation during the subsequent 24 h. Accumulation of free CNCbl and (OHCbl) was 1.4, (4.1) (liver); 20.2, (16.4) (kidney); and 0.05, (0.02) (plasma)% 24 h after administration. Total organ accumulations were 21.6, (20.5)%. While total accumulations of CNCbl and OHCbl were equal, distributions between liver, kidney, and plasma showed significant differences (p < 0.0001; p = 0.01; p < 0.0001).
CONCLUSIONS
Cbl added to milk (spiked with rbTC) has high bioavailability matching that of free Cbl. OHCbl and CNCbl are absorbed equally well, but much more OHCbl accumulated in the liver. Benefits of oral supplementation with OHCbl compared to CNCbl should be investigated.
Topics: Adsorption; Animals; Cattle; Male; Milk Proteins; Rats; Rats, Wistar; Recombinant Proteins; Transcobalamins; Vitamin B 12
PubMed: 26626348
DOI: 10.1016/j.biochi.2015.11.024 -
Biochimie May 2013Cellular uptake of cobalamin is facilitated by a receptor-mediated endocytosis process involving transcobalamin, a plasma protein that binds cobalamin and a cell surface... (Review)
Review
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 proliferating cells and an efflux system that shunts the excess cobalamin out of the cells for mobilization to other tissues where it is most needed. This review describes the process, proteins involved and genes encoding these proteins.
Topics: Animals; Humans; Receptors, Cell Surface; Transcobalamins; Vitamin B 12
PubMed: 23415653
DOI: 10.1016/j.biochi.2013.02.004 -
Caspian Journal of Internal Medicine 2023The changes of plasma transcobalamin-II (TCII) and Zinc (Zn) Levels in epileptic patients are not clearly understood. The aim of the current study was to evaluate the...
BACKGROUND
The changes of plasma transcobalamin-II (TCII) and Zinc (Zn) Levels in epileptic patients are not clearly understood. The aim of the current study was to evaluate the plasma contents of TCII and Zn levels in newly-diagnosed epileptic seizure patients, long-standing grand mal epileptic patients following treatment with sodium valproate and healthy control group.
METHODS
Thirty patients aged 36.76±12.91 years with newly-diagnosed and thirty long-standing grand mal epileptic patients aged 35.56 ±12.77 years were diagnosed based on the clinical symptoms. The control subjects were picked out from healthy individuals and matched to the patients, aged 36.30 ±12.80 years. Plasma Zn and TCN-2 was evaluated via spectrophotometry at 546 nm and 450 nm, respectively, using chimerical kits.
RESULTS
Plasma level of TCII in the newly-diagnosed epileptic seizures patients and long-standing grand mal epileptic patients were significantly increased, compared to the healthy controls [14.89 ±3.24 and 21.84± 2.73 vs. 9.55±1.24, (n=30)], respectively. Plasma level of Zn was decreased in the newly-diagnosed epileptic seizure patients, while it was increased in long-standing grand mal epileptic patients compared to the control group [69.28± 6.41 and 80.56 ±6.12 and vs.75.80±1.59, (n=30)], respectively.
CONCLUSION
This study suggests that sodium valproate may disrupt the homeostatic balance of TCII and Zn, and cause abnormality of their serum level in newly-diagnosed epileptic seizure patients and long-standing grand mal epileptic patients. Further research is recommended to identify the underpinning for these changes.
PubMed: 37223292
DOI: 10.22088/cjim.14.2.199