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Free vitamin B 12 and transcobalamin II-vitamin B 12 complex uptake by the visceral yolk sac of the sprague-dawley rat: Effect of inhibitors  

Microsoft Academic Search

Exogenous free vitamin B12 or B12 bound to human transcobalamin II (TCII) accumulated in the near-term rat visceral yolk sac. The rates of their uptakes in vitro and in vivo increased rapidly with time then reached a plateau, which supports a saturable transport\\/binding process as the rate-limiting step for the uptake of free and TCII complexed B12. Both uptakes were

Bruno M Polliotti; Maurice Panigel; Richard K Miller



Vitamin B12  


... with other B vitamins, such as niacin, riboflavin, vitamin B6, and magnesium. A prescription form of vitamin B12 ... Nutrition Board. Dietary Reference Intakes: Thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline . ...


Vitamin B12  


... vitamin B12 deficiency.Vitamin CEarly research suggests that vitamin C supplements can destroy dietary vitamin B12. It isn' ... but to stay on the safe side, take vitamin C supplements at least 2 hours after meals.


Vitamin B1 and B12 Uptake and Cycling by Plankton Communities in Coastal Ecosystems  

PubMed Central

While vitamin B12 has recently been shown to co-limit the growth of coastal phytoplankton assemblages, the cycling of B-vitamins in coastal ecosystems is poorly understood as planktonic uptake rates of vitamins B1 and B12 have never been quantified in tandem in any aquatic ecosystem. The goal of this study was to establish the relationships between plankton community composition, carbon fixation, and B-vitamin assimilation in two contrasting estuarine systems. We show that, although B-vitamin concentrations were low (pM), vitamin concentrations and uptake rates were higher within a more eutrophic estuary and that vitamin B12 uptake rates were significantly correlated with rates of primary production. Eutrophic sites hosted larger bacterial and picoplankton abundances with larger carbon normalized vitamin uptake rates. Although the >2??m phytoplankton biomass was often dominated by groups with a high incidence of vitamin auxotrophy (dinoflagellates and diatoms), picoplankton (<2??m) were always responsible for the majority of B12-vitamin uptake. Multiple lines of evidence suggest that heterotrophic bacteria were the primary users of vitamins among the picoplankton during this study. Nutrient/vitamin amendment experiments demonstrated that, in the Summer and Fall, vitamin B12 occasionally limited or co-limited the accumulation of phytoplankton biomass together with nitrogen. Combined with prior studies, these findings suggest that picoplankton are the primary producers and users of B-vitamins in some coastal ecosystems and that rapid uptake of B-vitamins by heterotrophic bacteria may sometimes deprive larger phytoplankton of these micronutrients and thus influence phytoplankton species succession.

Koch, Florian; Hattenrath-Lehmann, Theresa K.; Goleski, Jennifer A.; Sanudo-Wilhelmy, Sergio; Fisher, Nicholas S.; Gobler, Christopher J.



The kidney in vitamin B12 and folate homeostasis: characterization of receptors for tubular uptake of vitamins and carrier proteins.  


Over the past 10 years, animal studies have uncovered the molecular mechanisms for the renal tubular recovery of filtered vitamin and vitamin carrier proteins. Relatively few endocytic receptors are responsible for the proximal tubule uptake of a number of different vitamins, preventing urinary losses. In addition to vitamin conservation, tubular uptake by endocytosis is important to vitamin metabolism and homeostasis. The present review focuses on the receptors involved in renal tubular recovery of folate, vitamin B12, and their carrier proteins. The multiligand receptor megalin is important for the uptake and tubular accumulation of vitamin B12. During vitamin load, the kidney accumulates large amounts of free vitamin B12, suggesting a possible storage function. In addition, vitamin B12 is metabolized in the kidney, suggesting a role in vitamin homeostasis. The folate receptor is important for the conservation of folate, mediating endocytosis of the vitamin. Interaction between the structurally closely related, soluble folate-binding protein and megalin suggests that megalin plays an additional role in the uptake of folate bound to filtered folate-binding protein. A third endocytic receptor, the intrinsic factor-B12 receptor cubilin-amnionless complex, is essential to the renal tubular uptake of albumin, a carrier of folate. In conclusion, uptake is mediated by interaction with specific endocytic receptors also involved in the renal uptake of other vitamins and vitamin carriers. Little is known about the mechanisms regulating intracellular transport and release of vitamins, and whereas tubular uptake is a constitutive process, this may be regulated, e.g., by vitamin status. PMID:16760376

Birn, Henrik



Vitamin B12  


... Vitamin B12 supplements (along with folic acid and vitamin B6) do not reduce the risk of getting heart ... the blood. Vitamin B12 (with folic acid and vitamin B6) can lower homocysteine levels, but scientists don't ...


Genetic Analysis of Components Involved in Vitamin B12 Uptake in Escherichia coli  

PubMed Central

The products of three genes are involved in cyanocobalamin (B12) uptake in Escherichia coli. btuB (formerly bfe), located at min 88 on the Escherichia coli linkage map, codes for a protein component of the outer membrane which serves as receptor for B12, the E colicins, and bacteriophage BF23. Four phenotypic classes of mutants varying in response to these agents were found to carry mutations that, based on complementation and reversion analyses, reside in the single btuB cistron. In one mutant class, ligand binding to the receptor appeared to be normal, but subsequent B12 uptake was defective. The level of receptor and rate of uptake were responsive to btuB gene dosage. Previous studies showed that the tonB product was necessary for energy-dependent B12 uptake but not for its binding. Other than those in tonB, no mutations that conferred insensitivity to group B colicins affected B12 utilization. The requirement for the btuB and tonB products could be bypassed by elevated levels of B12 (>1 ?M) or by mutations compromising the integrity of the outer membrane as a permeability barrier. Utilization of elevated B12 concentrations in strains lacking the btuB-tonB uptake system was dependent on the function of the btuC product. This gene was located at 37.7 min on the linkage map, with the order pps-btuC-pheS. Strains altered in btuC but with an intact btuB-tonB system were only slightly impaired in B12 utilization, being defective in its accumulation. This defect was manifested as inability to retain B12, such that intracellular label was almost completely lost by exchange or efflux. It is proposed that btuC encodes a transport system for B12 in the periplasm.

Bassford, Philip J.; Kadner, Robert J.



Vitamin B12 benefits (image)  


Vitamin B12 is important for metabolism. Metabolism within the body includes the processes of energy generation and use; including nutrition, digestion, absorption, elimination, respiration, circulation, and temperature ...


Biosynthesis of Vitamin B 12  

Microsoft Academic Search

Vitamin B12 (cyanocobalamin) is the normal isolated form of coenzyme B12 (adenosylcobalamin), a structure of marvellous architecture and amazing biological activity. It belongs to the family of\\u000a tetrapyrroles which includes inter alia the haems and the chlorophylls. This review begins with a brief overview of the biosynthesis\\u000a of tetrapyrroles in general but then concentrates on recent research on B12 biosynthesis.

Alan R. Battersby; Finian J. Leeper


Functional implications of vitamin B(12) deficiency.  


Vitamin B(12) deficiency is a common but underrecognized problem in older adults. Historically, B(12) deficiency was diagnosed once a severe pernicious anemia developed. Scientific developments have led to a new understanding of a broader spectrum of B(12) deficiency and identification of a milder form of deficiency associated with food/vitamin B(12) malabsorption. Using an individual example, this article describes the functional impact of vitamin B(12) deficiency and highlights modern approaches to diagnosis and treatment. PMID:20506933

Cadogan, Mary P



Improved vitamin B(12) production by step-wise reduction of oxygen uptake rate under dissolved oxygen limiting level during fermentation process.  


Effects of different oxygen transfer rates (OTR) on the cell growth and vitamin B(12) biosynthesis of Pseudomonas denitrificans were first investigated under dissolved oxygen limiting conditions. The results demonstrated that high OTR accelerated cell growth and initial vitamin B(12) biosynthesis rate, while lower OTR was critical for higher productivity in the late fermentation process. The oxygen uptake rates (OUR) corresponded well with OTR. Based on the metabolic intermediate analysis, a step-wise OUR control strategy was proposed. The strategy was successfully implemented in scale-up to an industrial fermenter (120,000 l). A stable maximum vitamin B(12) production of 208 + or - 2.5 mg/l was achieved, which was increased by 17.3% compared with the control. Furthermore, the glucose consumption coefficient to vitamin B(12) was 34.4% lower than that of the control. An efficient and economical fermentation process based on OUR criterion was established for industrial vitamin B(12) fermentation by P. denitrificans. PMID:20022743

Wang, Ze-Jian; Wang, Hui-Yuan; Li, Yong-Liang; Chu, Ju; Huang, Ming-Zhi; Zhuang, Ying-Ping; Zhang, Si-Liang



Serum vitamin B12 not reflecting vitamin B12 status in patients with type 2 diabetes.  


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 sex distribution. We measured vitamin B12 markers [MMA, total serum vitamin B12, holoTC, total homocysteine (tHcy)], red blood cell (RBC)-B12, and the plasma concentrations of the methylation markers [S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH)]. In comparison to controls, diabetic patients showed significantly higher concentrations of plasma SAH (median 15.1 vs. 11.8 nmol/L; p < 0.001) and lower SAM/SAH ratio (9.1 vs. 8.2; p = 0.006). Concentrations of total vitamin B12 and holoTC did not differ significantly between the groups, but plasma MMA concentrations were significantly higher in diabetics (250 vs. 206 nmol/L). However, RBC-B12 was lower in diabetics compared to controls (median 230 vs. 260 pmol/L; p = 0.001). The inverse correlation between MMA and RBC-B12 was stronger in the controls compared to that in the patients (correlation coefficient in controls R = -0.446, p = 0.001; in patients R = -0.289, p = 0.022). Metformin treatment was associated with a lower total serum vitamin B12, but a comparable RBC-B12 and a slightly lower MMA and better methylation index. In conclusion, patients with type 2 diabetes showed normal extracellular vitamin B12, but disturbed intracellular B12-dependent biochemical reactions. Metformin treatment was associated with low serum vitamin B12 and improved intracellular vitamin B12 metabolism despite low serum vitamin B12. PMID:23168250

Obeid, Rima; Jung, John; Falk, Julia; Herrmann, Wolfgang; Geisel, Jürgen; Friesenhahn-Ochs, Bettina; Lammert, Frank; Fassbender, Klaus; Kostopoulos, Panagiotis



Assay for vitamin B12 absorption and method of making labeled vitamin B12  


The invention provides methods for labeling vitamin B12 with .sup.14C, .sup.13C, tritium, and deuterium. When radioisotopes are used, the invention provides for methods of labeling B12 with high specific activity. The invention also provides labeled vitamin B12 compositions made in accordance with the invention.

Anderson, Peter J. (Davis, CA); Dueker, Stephen (Davis, CA); Miller, Joshua (Davis, CA); Green, Ralph (Elmacero, CA); Roth, John (Davis, CA); Carkeet, Colleen (Silver Spring, MD); Buchholz,; Bruce A. (Orinda, CA)



Molecular Structure of Vitamin B12  

NSDL National Science Digital Library

Vitamin B12 (cyanocobalamin) has many uses as a nutritional supplement in both humans and livestock. It is used in humans to treat pernicious anemia, hepatitis, cirrhosis of the liver, and to help maintain the body's metabolism. In its long-effect form (hydroxocobalamin), vitamin B12 is used to treat anemia, growth impediment, improvement in the function of the heart, liver, kidneys and nerves, and general strengthening of the body. In livestock, it is used to improve feed production.



Indications for Vitamin B12 Therapy  

PubMed Central

A retrospective chart audit was undertaken to determine the clinical reasons for vitamin B12 therapy in family practice. Abnormal laboratory tests and symptoms were the most common reasons for initiating therapy. The high proportion of cases with little supporting evidence of B12 deficiency suggests that other factors influence treatment decisions.

Delva, M. Dianne; Anderson, J.E.



Placental transport of vitamin B12 in the pregnant rat  

PubMed Central

Placental transport of vitamin B12 was studied in the pregnant rat in two series of experiments. In the first series animals were given cyanocobalamin-57Co intravenously at various stages of gestation. High specific activity tracer was used and doses of B12 were 1-2 ng per animal. The rats were killed from 15 min to 24 hr after injection and the fetuses, placentas, and serum were assayed for radioactivity. In the second series using uninjected animals, absolute amounts of vitamin B12 in fetuses and placentas were measured at stages of gestation from day 12 through day 20. There was a progressive increase in B12 transferred to the fetus during gestation. Although the quantity of vitamin B12 transported per 24 hr was proportional to fetal weight, the amount transported per gram of placenta increased tenfold from day 10 through day 19. Uptake of tracer B12 by placenta was initially rapid; however, no radioactivity appeared in the fetus until 2 hr after injection. The actual amount of B12 in placenta increased throughout gestation, and the placental concentration of B12 was greater than maternal plasma and fetal tissue concentrations at all times measured. These data suggest that the ability of placenta to transport B12 increased throughout gestation, and that the rate-limiting step in the transport process was either the passage of B12 from the maternal to the fetal side of placenta or the transfer from placenta into fetal plasma.

Graber, Stanley E.; Scheffel, Ursula; Hodkinson, Barbara; McIntyre, Patricia A.



[Folate, vitamin B12 and human health].  


During the past decade the role of folate and vitamin B12 in human nutrition have been under constant re-examination. Basic knowledge on the metabolism and interactions between these essential nutrients has expanded and multiple complexities have been unraveled. These micronutrients have shared functions and intertwined metabolic pathways that define the size of the "methyl donor" pool utilized in multiple metabolic pathways; these include DNA methylation and synthesis of nucleic acids. In Chile, folate deficiency is virtually nonexistent, while vitamin B12 deficiency affects approximately 8.5-51% depending on the cut-off value used to define deficiency. Folate is found naturally mainly in vegetables or added as folic acid to staple foods. Vitamin B12 in its natural form is present only in foods of animal origin, which is why deficit is more common among strict vegetarians and populations with a low intake of animal foods. Poor folate status in vulnerable women of childbearing age increases the risk of neural tube birth defects, so the critical time for the contribution of folic acid is several months before conception since neural tube closure occurs during the first weeks of life. The absorption of vitamin B12 from food is lower in older adults, who are considered to have higher risk of gastric mucosa atrophy, altered production of intrinsic factor and acid secretion. Deficiency of these vitamins is associated with hematological disorders. Vitamin B12 deficiency can also induce clinical and sub-clinical neurological and of other disorders. The purpose of this review is to provide an update on recent advances in the basic and applied knowledge of these vitamins relative to human health. PMID:23677195

Brito, Alex; Hertrampf, Eva; Olivares, Manuel; Gaitán, Diego; Sánchez, Hugo; Allen, Lindsay H; Uauy, Ricardo



Production of vitamin B 12 in genetically engineered Propionibacterium freudenreichii  

Microsoft Academic Search

Since the chemical synthesis of vitamin B12 requires more than 70 steps, the production of vitamin B12 has been achieved by microorganism fermentation with additional brief chemical modifications. In an effort to increase the productivity of vitamin B12, we tried to express 10 genes belonging to the hem, cob and cbi gene families involved in the synthesis of vitamin B12

Yongzhe Piao; Mitsuo Yamashita; Nami Kawaraichi; Ryo Asegawa; Hisayo Ono; Yoshikatsu Murooka



Effect of bile on vitamin B12 absorption.  

PubMed Central

The standard double-isotope Schilling test was used to study vitamin B12 absorption in seven patients with obstructive jaundice and 10 with T-tube bile duct drainage after cholecystectomy and bile duct exploration. In three and five of these patients respectively absorption was impaired. In the second group six patients were restudied after removal of the T tube, and in each case absorption was improved. Similar results were obtained after bile duct ligation in rats. Bile exclusion produced a 50-60% reduction in renal and hepatic uptake of vitamin B12 from the intestinal lumen. The malabsorption was corrected by replacing bile. These studies suggest that bile plays a part in the normal absorption of vitamin B12.

Teo, N H; Scott, J M; Neale, G; Weir, D G



Content and characteristics of vitamin B12 in some seaweeds.  


The vitamin B12 (B12) content in seven species of seaweed that are consumed frequently in Hokkaido, Japan, was microbiologically measured using Escherichia coli 215. Asakusanori (Porphyra tenera), maruba-amanori (Porphyra suborbiculata) and akaba-gin-nansou (rhodo-glossum pulcherum) showed higher B12 content than the other species, although the content varied greatly among samples in the same species. A bioautography on a thin-layer plate holding a mixture of silica gel and cellulose, differentiation of B12 and its analogues using a binding specificity of intrinsic factor and haptocorrin, and comparison of the B12 concentration determined by the radioisotope dilution assay method using the intrinsic factor as the B12-binding protein with that by the bioassay method, predominantly showed B12 in maruba-amanori and B12 analogues in wakame (Undaria pinnatifida) and akaba-gin-nansou. The B12 uptake of akaba-gin-nansou from artificial seawater was similar to that of asakusanori that contained only B12. PMID:9089476

Yamada, S; Shibata, Y; Takayama, M; Narita, Y; Sugawara, K; Fukuda, M



The Soluble Receptor for Vitamin B12 Uptake (sCD320) Increases during Pregnancy and Occurs in Higher Concentration in Urine than in Serum  

PubMed Central

Background Cellular uptake of vitamin B12 (B12) demands binding of the vitamin to transcobalamin (TC) and recognition of TC-B12 (holoTC) by the receptor CD320, a receptor expressed in high quantities on human placenta. We have identified a soluble form of CD320 (sCD320) in serum and here we present data on the occurrence of this soluble receptor in both serum and urine during pregnancy. Methods We examined serum from twenty-seven pregnant women (cohort 1) at gestational weeks 13, 24 and 36 and serum and urine samples from forty pregnant women (cohort 2) tested up to 8 times during gestational weeks 17-41. sCD320, holoTC, total TC and complex formation between holoTC and sCD320 were measured by in-house ELISA methods, while creatinine was measured on the automatic platform Cobas 6000. Size exclusion chromatography was performed on a Superdex 200 column. Results Median (range) of serum sCD320 increased from 125 (87-839) pmol/L (week 15) to reach a peak value of 199 (72-672) pmol/L (week 35) then dropped back to its baseline level just before birth (week 40). Around one third of sCD320 was precipitated with holoTC at all-time points studied. The urinary concentration of sCD320 was around two fold higher than in serum. Urinary sCD320/creatinine ratio correlated with serum sCD320 and reached a peak median level of 53 (30–101) pmol/mmol creatinine (week 35). sCD320 present in serum and urine showed the same elution pattern upon size exclusion chromatography. Conclusion We report for the first time that sCD320 is present in urine and in a higher concentration than in serum and that serum and urine sCD320 increase during pregnancy. The high urinary concentration and the strong correlation between urinary and serum sCD320 suggests that sCD320 is filtered in the kidney.

Abuyaman, Omar; Andreasen, Birgitte H.; Kronborg, Camilla; Vittinghus, Erik; Nexo, Ebba



Pulse-Radiolysis Studies of the Vitamin B12 System.  

National Technical Information Service (NTIS)

The mechanisms and rates of some reduction processes in the vitamin B12 system were investigated by the technique of pulsed-electron radiolysis. In this way, it was shown that vitamin B12 and B12a (cyano- and hydroxocobalamin) react in rather different wa...

A. Y. Erkol



Genetic variation in vitamin B-12 content of bovine milk and its association with SNP along the bovine genome.  


Vitamin B-12 (also called cobalamin) is essential for human health and current intake levels of vitamin B-12 are considered to be too low. Natural enrichment of the vitamin B-12 content in milk, an important dietary source of vitamin B-12, may help to increase vitamin B-12 intake. Natural enrichment of the milk vitamin B-12 content could be achieved through genetic selection, provided there is genetic variation between cows with respect to the vitamin B-12 content in their milk. A substantial amount of genetic variation in vitamin B-12 content was detected among raw milk samples of 544 first-lactation Dutch Holstein Friesian cows. The presence of genetic variation between animals in vitamin B-12 content in milk indicates that the genotype of the cow affects the amount of vitamin B-12 that ends up in her milk and, consequently, that the average milk vitamin B-12 content of the cow population can be increased by genetic selection. A genome-wide association study revealed significant association between 68 SNP and vitamin B-12 content in raw milk of 487 first-lactation Dutch Holstein Friesian cows. This knowledge facilitates genetic selection for milk vitamin B-12 content. It also contributes to the understanding of the biological mechanism responsible for the observed genetic variation in vitamin B-12 content in milk. None of the 68 significantly associated SNP were in or near known candidate genes involved in transport of vitamin B-12 through the gastrointestinal tract, uptake by ileum epithelial cells, export from ileal cells, transport through the blood, uptake from the blood, intracellular processing, or reabsorption by the kidneys. Probably, associations relate to genes involved in alternative pathways of well-studied processes or to genes involved in less well-studied processes such as ruminal production of vitamin B-12 or secretion of vitamin B-12 by the mammary gland. PMID:23626813

Rutten, Marc J M; Bouwman, Aniek C; Sprong, R Corinne; van Arendonk, Johan A M; Visker, Marleen H P W



Vitamin B12-Containing Plant Food Sources for Vegetarians  

PubMed Central

The usual dietary sources of Vitamin B12 are animal-derived foods, although a few plant-based foods contain substantial amounts of Vitamin B12. To prevent Vitamin B12 deficiency in high-risk populations such as vegetarians, it is necessary to identify plant-derived foods that contain high levels of Vitamin B12. A survey of naturally occurring plant-derived food sources with high Vitamin B12 contents suggested that dried purple laver (nori) is the most suitable Vitamin B12 source presently available for vegetarians. Furthermore, dried purple laver also contains high levels of other nutrients that are lacking in vegetarian diets, such as iron and n-3 polyunsaturated fatty acids. Dried purple laver is a natural plant product and it is suitable for most people in various vegetarian groups.

Watanabe, Fumio; Yabuta, Yukinori; Bito, Tomohiro; Teng, Fei



Synthesis and biological activity of ribose-5'-carbamate derivatives of vitamin B(12).  


Twelve biologically active derivatives of vitamin B(12) (cyanocobalamin) have been synthesized in which spacers were attached to the ribose-5'-hydroxyl group of vitamin B(12). Their potential to act as oral delivery agents for proteins, nanospheres, or immunogens using the vitamin B(12) uptake system was evaluated by determining their affinity for intrinsic factor (IF) and non-IF. The ribose-5'-hydroxyl group of vitamin B(12) was activated through the use of 1,1'-carbonyldiimidazole (CDI), 1,1'-carbonyldi(1,2, 4-triazole) (CDT), or di(1-benzotriazolyl) carbonate (DBTC). Subsequent addition of an aminoalkane, diaminoalkane, or alkane diacid dihydrazide gave rise to vitamin B(12) derivatives suitable for attachment to various proteins, peptides, or nanospheres to enable oral delivery utilizing the vitamin B(12) uptake system. The ribose-5'-carbamate derivatives were found to possess similar affinity for intrinsic factor as that of the e-monocarboxylic acid of vitamin B(12). The affinity for non-IF was similar to cyanocobalamin or even higher for some of the smaller derivatives. Polysciences nanoparticles derivatized with vitamin B(12) 5'-carbamate adipic dihydrazide into CaCo-2 cells showed significantly higher levels of transport of the particles, when compared to unmodified particles. PMID:10563784

McEwan, J F; Veitch, H S; Russell-Jones, G J



Vitamin B 12 absorption and exocrine pancreatic insufficiency in childhood  

Microsoft Academic Search

The absorption of vitamin B12, labelled with radioactive 58Co, was measured in 19 patients with cystic fibrosis and one child with the Shwachman-Diamond syndrome using the whole body counting technique. We found vitamin B12 absorption reduced to 7.97% on average, compared to 59.2% for the control group. The low vitamin B12 absorption correlated well with the reduced fat retention coefficients.

H. K. Harms; O. Kennel; R. M. Bertele; F. Bidlingmeier; A. Böhne



Vitamin B12 Deficiency due to Chlorofluorocarbon: A Case Report  

PubMed Central

Background. Vitamin B12 is vital for optimal functioning of various organ systems but more importantly the central nervous system and the hematological system. Deficiency of vitamin B12 clinically manifests as excessive daytime fatigue, memory difficulties, encephalopathy, myelopathy, peripheral neuropathy, and optic neuropathy. In occupational medicine, vitamin B12 deficiency has been reported with exposure to nitrous oxide in health care workers. However, not much is known about exposure to Freons in other industries and vitamin B12 deficiency. Aim. We are reporting a case of vitamin B12 deficiency in the setting of exposure to chlorofluorocarbon (CFC) gases. Case Report. A 55-year-old male refrigerator mechanic experienced recurrent visual symptoms, which included diplopia and blurring. A complete workup was done and was significant of vitamin B12 deficiency. However, his B12 levels were refractory to supplementation. Appropriate precautions at workplace improved patient's symptoms and were associated with significant improvement in B12 levels. Conclusion. To the best of our knowledge, this is the first reported case of vitamin B12 deficiency (that remains refractory to supplementation) in the setting of exposure to Freon gases.

Bhaskar, Hemlata; Chaudhary, Rekha



Metabolic Changes Associated with Recovery from Vitamin B12 Deficiency.  

National Technical Information Service (NTIS)

After vitamin B12 therapy for deficiency of vitamin B12 in four cases of pernicious anemia, the following changes were observed in sequence: a decline in plasma folate, a decline in plasma iron, a rise in red cell folate coincident with the appearance of ...

C. E. Butterworth C. W. Scott E. Magnus R. Santini H. Dempsey



21 CFR 184.1945 - Vitamin B12.  

Code of Federal Regulations, 2010 CFR

...SAFE Listing of Specific Substances Affirmed as GRAS § 184.1945 Vitamin B12. (a) Vitamin B12 , also known as cyanocobalamin (C63 H88 CoN14 O14 P, CAS Reg. No. 68-0919-099), is produced commercially from cultures of...



Production of vitamin B12 in genetically engineered Propionibacterium freudenreichii.  


Since the chemical synthesis of vitamin B12 requires more than 70 steps, the production of vitamin B12 has been achieved by microorganism fermentation with additional brief chemical modifications. In an effort to increase the productivity of vitamin B12, we tried to express 10 genes belonging to the hem, cob and cbi gene families involved in the synthesis of vitamin B12 in Propionibacterium freudenreichii, which is a known producer of vitamin B12. In a recombinant P. freudenreichii clone that harbored the expression vector containing a cobA, cbiLF, or cbiEGH, we obtained an increase in vitamin B12 production of 1.7-, 1.9-, and 1.5-fold higher, respectively, than that in the microorganism without any cloned genes in the expression vector pPK705. The cobU and cobS genes caused a slight increase in the production of vitamin B12. Furthermore, we achieved multigene expression in P. freudenreichii. In a recombinant P. freudenreichii clone that harbored an exogenous gene, hemA, from Rhodobacter sphaeroides and endogenous hemB and cobA genes, we successfully achieved the production of about 1.7 mg/l vitamin B12, 2.2-fold higher than that produced by P. freudenreichii harboring pPK705. PMID:16233685

Piao, Yongzhe; Yamashita, Mitsuo; Kawaraichi, Nami; Asegawa, Ryo; Ono, Hisayo; Murooka, Yoshikatsu



Vitamin B12 content in raw and cooked beef.  


The aim of this work was to evaluate the vitamin B12 content and profile of cobalamin bioactive forms in raw and cooked beef. The study showed that vitamin B12 distribution is unequal among beef muscles. The content of this nutrient ranges from 0.7 to 1.5 ?g/100 g of tissue. In beef, three biologically active forms of vitamin B12 were determined, i.e.: methylcobalamin, adenosylcobalamin and hydroxycobalamin; the dominating form of vitamin B12 was adenosylcobalamin (68% of total cobalamins). The process of roasting and grilling had little effect on the vitamin B12 content in the final product as compared to the raw meat. The fried product was characterised by about a 32% lower content of cobalamins than in raw meat. PMID:24361556

Czerwonka, Ma?gorzata; Szterk, Arkadiusz; Waszkiewicz-Robak, Bo?ena



Cobalamin (Vitamin B12) and B12 Binding Proteins in Hypereosinophilic Syndromes and Secondary Eosinophilia  

Microsoft Academic Search

Serum cobalamin (vitamin B12) and unsaturated B12 binding capacity (UBBC) have been measured in 24 cases of hyper- eosinophilia: 1 6 were cases of hypereosinophilic syndrome (HES) and 8 of secondary eosinophilia. The two groups were similar with respect to absolute eosinophil counts. Serum cobalamin and UBBC were found to be markedly increased in most cases of HES and normal

Jacqueline Zittoun; Jean Pierre Farcet; Jeanine Marquet; Claude Sultan; Robert Zittoun



Microsoft Academic Search

Much attention has been focused on recent reports in which crude vitamin B12 (animal protein factor) supplements, as well as pure vitamin B12 and antibiotics, have been included in rations for chickens and swine, the claim being made, as a result of this work, that the animals gained weight more rapidly and usually more efficiently than did other animals consuming



Bioavailability of dietary cyanocobalamin (vitamin B12) in growing pigs.  


The present project aimed to estimate bioavailability of dietary vitamin B(12), for which little information is available in growing pigs. Two approaches, each using 2 quantities of dietary cyanocobalamin, were compared; the first was based on whole body retention for 8 d and the second was based on nycthemeral portal net flux of vitamin B(12). In the first trial, 15 blocks of 3 pigs (31.7 ± 0.5 kg of BW) were formed according to their vitamin B(12) status. Within each block, 1 pig (CONT) was killed and tissues were sampled for vitamin B(12) determination. The remaining 2 piglets were fed 25 (B(12)-25) or 250 (B(12)-250) ?g daily of cyanocobalamin for 8 d. Urine was sampled twice daily, and the pigs were killed and sampled as CONT pigs. The total content of vitamin B(12) in the carcass, urine, and intestinal tract was affected by the dietary treatments (P < 0.01) but not in the liver (P > 0.019). The whole body retention of vitamin B(12) was greater (P = 0.02) in B(12)-250 than B(12)-25 pigs, but the corresponding bioavailability was estimated to be 5.3 and 38.2%, respectively. In trial 2, 11 pigs (35.1 ± 4.0 kg of BW and 75.4 ± 5.9 d of age) fed a diet unsupplemented with vitamin B(12) from weaning at 28 d of age were surgically equipped with catheters in the portal vein and carotid artery and an ultrasonic flow probe around the portal vein. Each pig received 3 boluses of 0 (B(12)-0), 25, and 250 ?g of dietary vitamin B(12) according to a crossover design. Postprandial nycthemeral arterial plasma concentrations of vitamin B(12) reached minimum values (P < 0.01) between 15 and 18 h postmeal that were 29.6, 15.6, and 10.0% less than the premeal values for B(12)-0, B(12)-25, and B(12)-250 pigs, respectively (linear, P < 0.01). The cumulative net flux of vitamin B(12) for 24 h corresponded to 2.4 and 5.1 µg for B(12)-25 and B(12)-250 treatments, respectively, and the corresponding bioavailability was estimated to be 9.7 and 2.0%, respectively. Although bioavailability estimates varied according to approaches, both showed the inverse relationship between dietary vitamin B(12) and bioavailability of the vitamin. The dietary supplement of 25 µg was sufficient to maximize hepatic vitamin B(12) retention and to attenuate the nycthemeral decrease of arterial plasma concentration of the vitamin. PMID:20709870

Matte, J J; Guay, F; Le Floc'h, N; Girard, C L



Regiospecificity of Chlorophenol Reductive Dechlorination by Vitamin B12s  

PubMed Central

Vitamin B12, reduced by titanium (III) citrate to vitamin B12s, catalyzes the reductive dechlorination of chlorophenols. Reductive dechlorination of pentachlorophenol and of all tetrachlorophenol and trichlorophenol isomers was observed. Reaction of various chlorophenols with vitamin B12 favored reductive dechlorination at positions adjacent to another chlorinated carbon, but chlorines ortho to the hydroxyl group of a phenol were particularly resistant to reductive dechlorination, even if they were also ortho to a chlorine. This resulted in a reductive dechlorination pattern favoring removal of para and meta chlorines, which differs substantially from the pattern exhibited by anaerobic microbial consortia.

Smith, Mark H.; Woods, Sandra L.



[Biosynthesis, fermentation and application of vitamin B12--a review].  


Vitamin B12 is an important nutrient widely used in feed, food and medicine field. China is the primary producing area and the VB12 production is 27 t in 2007, 77% of total production in the world. VB12 is the most complex small molecule difficult to chemosynthesize. It ismanufactured by bacteria and archaea via two alternative routes, aerobic or anaerobic pathway. The main strains used in industry fermentation are Propionibacterium freudenrechii and Pseudomonas denitrificans. The basic characteristics, biosynthesis and fermentation of vitamin B12 are reviewed. The vitamin B12 application and market are also summarized. PMID:18807971

Ma, Hui; Wang, Lili; Zhang, Chunxiao; Yi, Hong



Neuroenhancement with Vitamin B12--Underestimated Neurological Significance  

PubMed Central

Vitamin B12 is a cofactor of methionine synthase in the synthesis of methionine, the precursor of the universal methyl donor S-Adenosylmethionine (SAMe), which is involved in different epigenomic regulatory mechanisms and especially in brain development. A Vitamin B12 deficiency expresses itself by a wide variety of neurological manifestations such as paraesthesias, skin numbness, coordination disorders and reduced nerve conduction velocity. In elderly people, a latent Vitamin B12 deficiency can be associated with a progressive brain atrophy. Moderately elevated concentrations of homocysteine (>10 µmol/L) have been associated with an increased risk of dementia, notably Alzheimer’s disease, in many cross-sectional and prospective studies. Raised plasma concentrations of homocysteine is also associated with both regional and whole brain atrophy, not only in Alzheimer’s disease but also in healthy elderly people. Clinician awareness should be raised to accurately diagnose and treat early Vitamin B12 deficiency to prevent irreversible structural brain damage.

Grober, Uwe; Kisters, Klaus; Schmidt, Joachim



Vitamin B 12 deficiency in untreated celiac disease  

Microsoft Academic Search

OBJECTIVES:Iron and folate malabsorption are common in untreated celiac disease as the proximal small intestine is predominantly affected. Vitamin B12 deficiency is thought to be uncommon, as the terminal ileum is relatively spared. This study aims to investigate the prevalence of vitamin B12 deficiency in patients with untreated celiac disease.METHODS:Prospective study of 39 consecutive biopsy-proven celiac disease patients (32 women,

Anna Dahele; Subrata Ghosh



Vitamin B12 deficiency in untreated celiac disease  

Microsoft Academic Search

OBJECTIVES:Iron and folate malabsorption are common in untreated celiac disease as the proximal small intestine is predominantly affected. Vitamin B12 deficiency is thought to be uncommon, as the terminal ileum is relatively spared. This study aims to investigate the prevalence of vitamin B12 deficiency in patients with untreated celiac disease.METHODS:Prospective study of 39 consecutive biopsy-proven celiac disease patients (32 women,

Anna Dahele; Subrata Ghosh



Proteomics of vitamin B12 processing.  


The causes of cobalamin (B12, Cbl) deficiency are multifactorial. Whether nutritional due to poor dietary intake, or functional due to impairments in absorption or intracellular processing and trafficking events, the major symptoms of Cbl deficiency include megaloblastic anemia, neurological deterioration and in extreme cases, failure to thrive and death. The common biomarkers of Cbl deficiency (hyperhomocysteinemia and methylmalonic acidemia) are extremely valuable diagnostic indicators of the condition, but little is known about the changes that occur at the protein level. A mechanistic explanation bridging the physiological changes associated with functional B12 deficiency with its intracellular processers and carriers is lacking. In this article, we will cover the effects of B12 deficiency in a cblC-disrupted background (also referred to as MMACHC) as a model of functional Cbl deficiency. As will be shown, major protein changes involve the cytoskeleton, the neurological system as well as signaling and detoxification pathways. Supplementation of cultured MMACHC-mutant cells with hydroxocobalamin (HOCbl) failed to restore these variants to the normal phenotype, suggesting that a defective Cbl processing pathway produces irreversible changes at the protein level. PMID:23241609

Hannibal, Luciana; DiBello, Patricia M; Jacobsen, Donald W



The electronic structure and chemical bonding of vitamin B12  

NASA Astrophysics Data System (ADS)

The electronic structure and chemical bonding of vitamin B12 (cyanocobalamin) and B12-derivative (methylcobalamin) are studied by means of X-ray emission (XES) and photoelectron (XPS) spectroscopy. The obtained results are compared with ab initio electronic structure calculations using the orthogonalized linear combination of the atomic orbital method (OLCAO). We show that the chemical bonding in vitamin B12 is characterized by the strong Co-C bond and relatively weak axial Co-N bond. It is further confirmed that the Co-C bond in cyanocobalamin is stronger than that of methylcobalamin resulting in their different biological activity.

Kurmaev, E. Z.; Moewes, A.; Ouyang, L.; Randaccio, L.; Rulis, P.; Ching, W. Y.; Bach, M.; Neumann, M.



Two newborns with nutritional vitamin B12 deficiency: challenges in newborn screening for vitamin B12 deficiency.  


Vitamin B12 deficiency causes decreased Methionine Synthase and L-Methylmalonyl-CoA Mutase activity and results in accumulation of Homocysteine, Methylmalonic acid and Propionylcarnitine. Propionylcarnitine is included in tandem mass spectrometry-based newborn screening programs for detection of certain inborn errors of metabolism. We report two asymptomatic newborns with Vitamin B12 deficiency due to maternal deficiencies. One was detected incidentally at 3 weeks of age; the second on supplemental newborn screening based on elevated Propionylcarnitine at 2 days of age. This illustrates the potential for false negative results for Vitamin B12 deficiency screening by acylcarnitine profiling in newborn screening. Homocysteine and Methylmalonic acid may be better markers of Vitamin B12 deficiency. In conclusion, we suggest measuring Methylmalonic acid, Propionylcarnitine and Homocysteine levels in blood spots in expanded newborn screening in order to detect asymptomatic newborns with Vitamin B12 deficiency. Further studies are needed to establish the sensitivity of these three markers in screening for Vitamin B12 deficiency. PMID:16464760

Campbell, C D; Ganesh, J; Ficicioglu, C



Idiopathic hypoparathyroidism with impaired vitamin B12 absorption and neuropathy  

PubMed Central

A 68-year-old man presenting with chronic intermittent diarrhea and progressive ataxia was found to have idiopathic hypoparathyroidism. Intrinsic factor-resistant vitamin B12 malabsorption was demonstrated. Both the diarrhea and vitamin malabsorption were reversed by correction of hypocalcemia. His neurological profile was a combination of peripheral nerve, posterior column and cerebellar deficits. He had calcifications in the dentate nuclei of the cerebellum. Possible etiological factors such as vitamin B12 deficiency, folic acid deficiency and steatorrhea have been excluded. Posterior column and cerebellar abnormalities improved with treatment. It is postulated that hypocalcemia causes functional, reversible spinal cord and cerebellar dysfunction. ImagesFIG. 1

Gay, John D. L.; Grimes, J. David



Vitamin B12 Status in Metformin Treated Patients: Systematic Review  

PubMed Central

Objective Randomized controlled trials and observational studies have yielded inconsistent results on the effects of metformin on vitamin B12 reduction. We therefore performed a systematic review to analyze the effects of metformin on vitamin B12 concentration. Methods PubMed, Medline, Embase, and the Cochrane central registry of controlled trials were searched to identify randomized controlled trials and observational studies exploring the association between metformin and vitamin B12 concentration in patients with type 2 diabetes mellitus or polycystic ovary syndrome. The main outcome measure was changes in serum vitamin B12 concentration after 6–208 weeks of treatment with metformin, as compared with placebo or other anti-hyperglycemic therapy. Results Six randomized controlled trials met the inclusion criteria. Serum vitamin B12 concentrations were significantly lower in patients treated with metformin than in those who received placebo or rosiglitazone (mean difference [MD], ?53.93 pmol/L; 95% confidence interval [CI], ?81.44 to ?26.42 pmol/L, P?=?0.0001). Subgroup analysis identified four trials in which patients received a lower dose of metformin (<2000 mg/d) and two in which they received a higher dose (?2000 mg/d), with MDs in vitamin B12 concentration after metformin treatment of ?37.99 pmol/L (95% CI, ?57.44 to ?18.54 pmol/L, P?=?0.0001) and ?78.62 pmol/L (95% CI, ?106.37 to ?50.86 pmol/L, P<0.00001), respectively. Conclusions The reduction of vitamin B12 may be induced by metformin in a dose dependent manner.

Quan, Heng; Li, Jianwei



Methylmalonic acidemia controlled with oral administration of vitamin B12.  

PubMed Central

A 3-month-old male infant had two episodes of fever, projectile vomiting, dehydration, generalized fine tremors and gross metabloic ketoacidosis. Methylmalonic acid was found in high concentration in both serum and urine, although the concentration of serum vitamin B12 was normal. A therapeutic trial of vitamin B12, administered parenterally, reduced greatly the methylmalonic aciduria. The patient has since been given vitamin B12 supplements continuously, initially 1 mg intramuscularly every other day, then 15 mg/d orally, and the protein in his diet was subsequently restricted. The most effected control of the methylmalonic aciduria was achieved with the combined regimen of oral vitamin therapy and dietary protein restriction. His physical and intellectual development have progressed normally and he has survived several acute respiratory tract infections without recurrence of metabolic acidosis.

Gordon, B. A.; Carson, R. A.



Thermotoga lettingae Can Salvage Cobinamide To Synthesize Vitamin B12  

PubMed Central

We recently reported that the Thermotogales acquired the ability to synthesize vitamin B12 by acquisition of genes from two distantly related lineages, Archaea and Firmicutes (K. S. Swithers et al., Genome Biol. Evol. 4:730–739, 2012). Ancestral state reconstruction suggested that the cobinamide salvage gene cluster was present in the Thermotogales' most recent common ancestor. We also predicted that Thermotoga lettingae could not synthesize B12 de novo but could use the cobinamide salvage pathway to synthesize B12. In this study, these hypotheses were tested, and we found that Tt. lettingae did not synthesize B12 de novo but salvaged cobinamide. The growth rate of Tt. lettingae increased with the addition of B12 or cobinamide to its medium. It synthesized B12 when the medium was supplemented with cobinamide, and no B12 was detected in cells grown on cobinamide-deficient medium. Upstream of the cobinamide salvage genes is a putative B12 riboswitch. In other organisms, B12 riboswitches allow for higher transcriptional activity in the absence of B12. When Tt. lettingae was grown with no B12, the salvage genes were upregulated compared to cells grown with B12 or cobinamide. Another gene cluster with a putative B12 riboswitch upstream is the btuFCD ABC transporter, and it showed a transcription pattern similar to that of the cobinamide salvage genes. The BtuF proteins from species that can and cannot salvage cobinamides were shown in vitro to bind both B12 and cobinamide. These results suggest that Thermotogales species can use the BtuFCD transporter to import both B12 and cobinamide, even if they cannot salvage cobinamide.

Butzin, Nicholas C.; Secinaro, Michael A.; Swithers, Kristen S.; Gogarten, J. Peter



Assessment of the Vitamin B12 Status of Pregnant Women in Nigeria Using Plasma Holotranscobalamin  

PubMed Central

Maternal vitamin B12 deficiency during pregnancy is an independent risk factor for neural tube defects and other neurological problems in infants. We determined the vitamin B12 status of 143 pregnant women in Nigeria representing all trimesters who presented to an antenatal clinic in Jos, Nigeria, using holotranscobalamin II levels (holoTCII), which is a measure of the vitamin B12 that is available for uptake into tissues. The holoTCII concentration ranged from 13 to 128?pmol/L. Using a cutoff of 40?pmol/L, 36% of the women were classified as vitamin B12-deficient. HoloTCII concentrations correlated negatively with plasma homocysteine levels (r = ?0.24, P = 0.003) and positively with red blood cell folate concentrations (r = 0.28, P < 0.001). These data underscore the importance of supplementing pregnant women in Nigeria with vitamin B12 in order to ensure adequate vitamin B12 status and decrease the risk for neural tube defects.

VanderJagt, Dorothy J.; Ujah, Innocent A. O.; Ikeh, Eugene I.; Bryant, Jessica; Pam, Victor; Hilgart, Amelia; Crossey, Michael J.; Glew, Robert H.



Seasonal distribution of vitamin B12 in Lake Kinneret.  

PubMed Central

Vitamin B12 is formed in Lake Kinneret in the hypolimnion and in the sediment. The highest value of B12 recorded in the lake water was about 100 ng/liter in November and December of 1975 at a 40-m depth. The vitamin was liberated from the hypolimnion during the turnover period. This supply of the vitamin to the photic zone was accompanied by increasing biomass of Dinoflagellates, Bacillariophyta, and Chlorophyta. The decrease in the vitamin concentration, followed by an increase, is correlated with a decline and subsequent rise in the algal biomass, respectively. Cyanophyta biomass, on the other hand, increased when the vitamin concentration in the photic zone was at its lowest level.

Cavari, B; Grossowicz, N



Oral contraceptives: effect of folate and vitamin B12 metabolism.  

PubMed Central

Women who use oral contraceptives have impaired folate metabolism as shown by slightly but significantly lower levels of folate in the serum and the erythrocytes and an increased urinary excretion of formiminoglutamic acid. The vitamin B12 level in their serum is also significantly lower than that of control groups. However, there is no evidence of tissue depletion of vitamin B12 associated with the use of oral contraceptives. The causes and clinical significance of the impairment of folate and vitamin B12 metabolism in these women is discussed in this review of the literature. Clinicians are advised to ensure that women who shop taking "the pill" because they wish to conceive have adequate folate stores before becoming pregnant.

Shojania, A. M.



Folate and vitamin B12 in idiopathic male infertility  

Microsoft Academic Search

Although methylenetetrahydrofolate reductase, a folate enzyme gene, has been associated with idiopathic male infertility, few studies have examined other folate-related metabolites and genes. We investigated whether idiopathic male infertility is associated with variants in folate, vitamin B12 (B12) and total homocysteine (tHcy)-related genes and measured these metabolites in blood. We conducted a case–control study that included 153 men with idiopathic

Laurel E Murphy; James L Mills; Anne M Molloy; Cong Qian; Tonia C Carter; Helena Strevens; Dag Wide-Swensson; Aleksander Giwercman; Richard J Levine



Vitamin B12 deficit and development of geriatric syndromes  

PubMed Central

Vitamin B12 deficiency or cyanocobalamin is a common condition in the elderly. It is repeatedly overlooked due to multiple clinical manifestations that can affect the blood, neurological, gastrointestinal, and cardiovascular systems, skin and mucous membranes. The various presentations of vitamin B12 deficiency are related to the development of geriatric syndromes like frailty, falls, cognitive impairment, and geriatric nutritional syndromes like protein-energy malnutrition and failure to thrive, in addition to enhancing aging anorexia and cachexia. Therefore, interventions must be developed to include their screening and diagnosis to make early and appropriate treatment to prevent its complications before they become irreversible.



Two outer membrane transport systems for vitamin B12 in Salmonella typhimurium.  

PubMed Central

The involvement of an outer membrane transport component for vitamin B12 uptake in Salmonella typhimurium, analogous to the btuB product in Escherichia coli, was investigated. Mutants of S. typhimurium selected for resistance to bacteriophage BF23 carried mutations at the btuB locus (butBS) (formerly called bfe, at the analogous map position as the E. coli homolog) and were defective in high-affinity vitamin B12 uptake. The cloned E. coli btuB gene (btuBE) hybridized to S. typhimurium genomic DNA and restored vitamin B12 transport activity to S. typhimurium btuBS mutants. An Mr-60,000 protein in the S. typhimurium outer membrane was repressed by growth with vitamin B12 and was eliminated in a btuBS mutant. The btuBS product thus appears to play the same role in vitamin B12 transport by S. typhimurium as does the E. coli btuBE product. A second vitamin B12 transport system that is not present in E. coli was found by cloning a fragment of S. typhimurium DNA that complemented btuB mutants for vitamin B12 utilization. In addition to this plasmid with a 6-kilobase insert of S. typhimurium DNA, vitamin B12 utilization by E. coli btuB strains required the btuC and btuD products, necessary for transport across the cytoplasmic membrane, but not the btuE or tonB product. The plasmid conferred low levels of vitamin B12-binding and energy-dependent transport activity but not susceptibility to phage BF23 or utilization of dicyanocobinamide. The cloned S. typhimurium DNA encoding this new transport system did not hybridize to the btuBE gene or to E. coli chromosomal DNA and therefore does not carry the S. typhimurium btuBS locus. Increased production of an Mr -84,000 polypeptide associated with the outer membrane was seen. The new locus appears to be carried on the large plasmid in most S. typhimurium strains. Thus S. typhimurium possesses both high- and low-affinity systems for uptake of cobalamins across the outer membrane. Images

Rioux, C R; Kadner, R J



High-dose compared with low-dose vitamin B-12 supplement use is not associated with higher vitamin B-12 status in children, adolescents, and older adults.  


Over-the-counter vitamin supplements on the Canadian market are permitted to contain a daily vitamin B-12 dose of up to 1000 ?g. Our objective was to determine the association between total daily vitamin B-12 supplement dose and markers of vitamin B-12 status in Canadians. Blood collected from a nationally representative sample aged 6-79 y (n = ?5600) in the Canadian Health Measures Survey (2007-2009) was analyzed for serum vitamin B-12 and plasma total homocysteine (tHcy). Total daily intake of vitamin B-12 from single and multivitamin supplements was calculated. Individuals that indicated proton pump inhibitor or vitamin B-12 injection treatment were excluded from the supplement dose and tHcy analyses; folate-deficient individuals were also excluded from the tHcy analysis. Twenty-three percent of children, 12.3% of adolescents, and 25.5% of adults consumed a vitamin B-12-containing supplement. Supplement users had 33% higher serum vitamin B-12 and 4.2% higher prevalence of adequacy than did non-supplement users. Children and adolescents consuming >10 ?g/d supplemental vitamin B-12 did not demonstrate higher serum vitamin B-12, higher prevalence of serum vitamin B-12 adequacy, or lower tHcy than did those consuming >0-10 ?g/d. The association between serum vitamin B-12 reached a plateau at doses of >25 and >10-25 ?g/d in adults aged 46-59 and 60-79 y, respectively. The prevalences of serum vitamin B-12 adequacy and normal tHcy, and tHcy did not differ by vitamin B-12 supplement dose in adults >45 y. In this cross-sectional study, vitamin B-12 supplement doses >10-25 ?g/d were not associated with higher vitamin B-12 status in children, adolescents, or older adults compared with lower doses. PMID:24699807

MacFarlane, Amanda J; Shi, Yipu; Greene-Finestone, Linda S



An amphiphilic, catalytically active, vitamin B12 derivative.  


We performed the reaction of vitamin B12 with N,N-dimethylformamide dimethyl acetal for primary amide activation, and added MeOH as a nucleophile, to afford cobalester, the first amphiphilic cobalamin derivative. The unique combination of redox properties and solubility represents an asset for its use as a catalyst in C-C bond forming reactions. PMID:24623153

Giedyk, M; Fedosov, S N; Gryko, D



Transport of vitamin B12 in Escherichia coli: cloning of the btuCD region.  

PubMed Central

The transport of vitamin B12 in Escherichia coli requires a specific vitamin B12 receptor protein in the outer membrane and the tonB gene product. In addition, the btuC gene, located at min 38 on the genetic map, has been found to influence vitamin B12 uptake or utilization. The btuC function is required for the growth response to vitamin B12 when the outer membrane transport process (btuB or tonB function) is defective. However, even in a wild-type strain, btuC is required for proper transport of vitamin B12. Additional mutations in the vicinity of btuC were isolated as lac fusions that produced a phenotype similar to that of a btuC mutant. The btuC region was cloned by selection for complementation of a btuC mutation. Complementation testing with plasmids carrying various deletions or transposon Tn1000 insertions demonstrated that the new mutations defined a separate, independently expressed locus, termed btuD. The coding regions for both genes were identified on a 3.4-kilobase HindIII-HincII fragment and were 800 to 1,000 base pairs in length. They were separated by a 600- to 800-base-pair region. The gene order in this portion of the chromosome map was found to be pps-zdh-3::Tn10-btuD-btuC-pheS. Expression of beta-galactosidase in the btuD-lac fusion-bearing strains, whether proficient or defective in vitamin B12 transport, was not regulated by the presence of vitamin B12 in the growth medium.

DeVeaux, L C; Kadner, R J



How prevalent is vitamin B(12) deficiency among vegetarians?  


Vegetarians are at risk for vitamin B(12) (B12) deficiency due to suboptimal intake. The goal of the present literature review was to assess the rate of B12 depletion and deficiency among vegetarians and vegans. Using a PubMed search to identify relevant publications, 18 articles were found that reported B12 deficiency rates from studies that identified deficiency by measuring methylmalonic acid, holo-transcobalamin II, or both. The deficiency rates reported for specific populations were as follows: 62% among pregnant women, between 25% and almost 86% among children, 21-41% among adolescents, and 11-90% among the elderly. Higher rates of deficiency were reported among vegans compared with vegetarians and among individuals who had adhered to a vegetarian diet since birth compared with those who had adopted such a diet later in life. The main finding of this review is that vegetarians develop B12 depletion or deficiency regardless of demographic characteristics, place of residency, age, or type of vegetarian diet. Vegetarians should thus take preventive measures to ensure adequate intake of this vitamin, including regular consumption of supplements containing B12. PMID:23356638

Pawlak, Roman; Parrott, Scott James; Raj, Sudha; Cullum-Dugan, Diana; Lucus, Debbie



Oral cobalamin (vitamin B(12)) treatment. An update.  


The objective of this review was to evaluate oral cobalamin (vitamin B(12)) therapy in adult and elderly patients, from the perspective of a hematologist. PubMed was systematically searched for English and French articles published from January 1990 to January 2007. Data from our working group, the 'Groupe d'étude des carences en vitamine B(12)des Hôpitaux Universitaires de Strasbourg', have also been included. Several prospective studies in well-determined population (n = 4), prospective randomized studies (n = 3) and a systematic review by the Cochrane group (n = 1) provide evidence that oral cobalamin therapy may adequately treat cobalamin deficiency, particularly hematological abnormalities or manifestations. These studies suggest that at least 1000 microg/day of oral cyanocobalmin are needed for pernicious anemia and a mean daily dose of 250 microg for food-cobalamin malabsorption. This present review confirms the previously reported efficacy of oral cobalamin treatment in adult and elderly patients. PMID:19032377

Andrès, E; Dali-Youcef, N; Vogel, T; Serraj, K; Zimmer, J



Dietary folate and vitamin B12 supplementation and consequent vitamin deposition in chicken eggs.  


We determined the effects of dietary supplementation with folate and vitamin B(12) on lipid metabolism and the deposition of these vitamins in eggs of laying hens (age 64-72 weeks). Four levels of folate (0, 0.5, 4 and 10 mg/kg) and three levels of vitamin B(12) (0, 0.01 and 0.08 mg/kg) were added to the basal diet for 8 weeks in a 4 x 3 factorial completely randomized design study. No significant physiological interaction between folate and vitamin B(12) was evident under our experimental conditions. There was no effect of vitamins supplementation on egg production or feed intake. Supplementation with folate significantly elevated serum (p < 0.01) and yolk (p < 0.05) folate levels. Supplementation with vitamin B(12) did not significantly affect serum or egg yolk vitamin B(12) levels. Supplementation with folate or vitamin B(12) did not significantly affect triglyceride or total phospholipid levels in serum or egg yolk although a positive relationship was observed between dietary folate supplementation and total serum phospholipid (r(2) = 0.68, p < 0.05). The study showed that it is possible to produce folate-enriched eggs. An increase in serum total phospholipids due to dietary supplementation with folate may provide physiological benefits to hens, although we did not observe any strong effects of these vitamins on lipid composition. PMID:19396565

Bunchasak, Chaiyapoom; Kachana, Sompong



Characterization and bioavailability of vitamin B12-compounds from edible algae.  


Substantial amounts of vitamin B12 were found in some edible algae (green and purple lavers) and algal health food (chlorella and spirulina tablets) using the Lactobacillus delbrueckii subsp. lactis ATCC7830 microbiological assay method. Corrinoid-compounds were purified and characterized from these algae to clarify the chemical properties and bioavailability of the algal vitamin B12. True vitamin B12 is the predominate cobamide of green and purple lavers and chlorella tablets. Feeding the purple laver to vitamin B12-deficient rats significantly improved the vitamin B12 status. The results suggest that algal vitamin B12 is a bioavailable source for mammals. Pseudovitamin B12 (an inactive corrinoid) predominated in the spirulina tablets, which are not suitable for use as a vitamin B12 source, especially for vegetarians. algal health food, bioavailability, cobalamin, edible algae, vitamin B12 PMID:12656203

Watanabe, Fumio; Takenaka, Shigeo; Kittaka-Katsura, Hiromi; Ebara, Shuhei; Miyamoto, Emi



Very low oral doses of vitamin B-12 increase serum concentrations in elderly subjects with food-bound vitamin B-12 malabsorption.  


The BOSSANOVA study, a randomized double-blind trial, was designed to test the ability of very low oral doses of vitamin B-12 to increase the serum vitamin B-12 concentration in elderly subjects with food-bound vitamin B-12 malabsorption, and to determine whether there was a dose response. We also aimed to quantitatively assess the most efficient dose to be added to flour in addition to folic acid (flour cofortification with vitamin B-12 and folic acid). Sixty-seven patients were randomly assigned to 1 of 6 groups receiving various daily oral doses of vitamin B-12 (i.e., 2.5, 5, 10, 20, 40, or 80 microg/d) for 30 d. The dose-response was tested for different biological variables using a mixed model, taking into account the variable's initial value (between-subject effect), a linear log-dose effect, and a linear log (dosextime) interaction, where time was d 15 or d 30. We planned to determine the amount of oral vitamin B-12 that would increase the serum vitamin B-12 concentration by 37 pmol/L (50 ng/L). Significant between-subject effects were found for serum vitamin B-12, plasma homocysteine, and methylmalonic acid concentrations, but a log-dose effect was found only for vitamin B-12 (P<0.001). The slope of the line tended to be higher (P=0.07) at d 30 than at d 15. For a mean serum vitamin B-12 increase of 37 pmol/L, a dose of 5.9 (95% CI, 0.9-12.1) microg/d was needed. We concluded that very low oral doses of vitamin B-12 increased serum vitamin B-12 concentrations in elderly subjects with subclinical vitamin B-12 deficiency, following a log-dose pattern. Our results could be beneficial in the design of a public health program for safe flour cofortification with folic acid. PMID:17237314

Blacher, Jacques; Czernichow, Sébastien; Raphaël, Mathilde; Roussel, Christophe; Chadefaux-Vekemans, Bernadette; Morineau, Gilles; Giraudier, Stéphane; Tibi, Annick; Henry, Olivier; Vayssière, Michel; Oudjhani, Moussa; Nadaï, Sophie; Vincent, Jean-Pierre; Bodak, Alexandre; Di Menza, Claude; Ménard, Joël; Zittoun, Jacqueline; Ducimetière, Pierre



Effect of gastrointestinal proteases on purified human intrinsic factor-vitamin B12 (IF-B12) complex.  


Intrinsic factor (IF) from human gastric juice was purified and complexed with vitamin B12 (IF-B12 complex) on Sepharose-vitamin B12 affinity matrix. By labeling studies, using [(57)Co] vitamin B12 and (125)I, the specific B12 binding activity of IF was found to be 23 microg B12/mg protein, and the molecular size by gel filtration 60 kDa. Proteolysis of the IF-B12 complex by sequential treatment with pepsin, trypsin, alpha-chymotrypsin and carboxypeptidase A, followed by chromatography of proteolysed complex and IF-B12 showed higher mobility of proteolysed fraction. Gel filtration, however, showed same molecular size for both proteolysed and the IF-B12 complex. On SDS-PAGE, purified IF-B12 appeared as a single band of 60 kDa. The proteolysed complex had higher mobility on SDS-PAGE and did not bind to zirconium phosphate gel. Immunodiffusion with rabbit antisera had positive reaction with IF-B12, but there was no reaction with the proteolysed sample. PMID:22900303

Srikumar, K; Premalatha, R



Dose-response effects of long-acting injectable vitamin B12 plus selenium (Se) on the vitamin B12 and Se status of ewes and their lambs  

Microsoft Academic Search

AIM: To determine the effect of increasing doses of long-acting injectable vitamin B12 plus selenium (Se) given pre-mating on the vitamin B12 and Se status of ewes and their lambs from birth to weaning.METHODS: Four groups of 24 Poll Dorset ewes each were injected 4 weeks pre-mating with different doses of a long-acting vitamin B12 + Se product, containing 3

ND Grace; SO Knowles



Neonatal vitamin B12 deficiency secondary to maternal subclinical pernicious anemia: identification by expanded newborn screening.  


A neonate with elevated propionylcarnitine on the newborn screen was found to have methylmalonic acidemia due to vitamin B(12) deficiency. The mother was also vitamin B(12)-deficient. This case illustrates the utility of expanded newborn screening for detection of vitamin B(12) deficiency, allowing prompt treatment and prevention of potential sequelae. PMID:18410783

Marble, Michael; Copeland, Sara; Khanfar, Nashat; Rosenblatt, David S



Effect of Vitamin B12 Deficiency on Liver Dehydrogenase Activity in Rats  

Microsoft Academic Search

WEANLING rats born of mothers maintained on a diet deficient in vitamin B12 during pregnancy were fed on a vitamin B12-free ration for twelve weeks and their liver dehydrogenase levels were compared with those of similar animals receiving 2-µgm. supplements of vitamin B12 daily. The basal diet had the composition : whole soya bean flour, 25; groundnut cake flour, 14;

V. Sreenivasa Murthy; H. S. R. Desikachar; M. Swaminathan



Vitamin B12 deficiency presenting as acute ataxia.  


A previously healthy 7-year-old Caucasian boy was hospitalised for evaluation of acute ataxia and failure to thrive, initially suspicious for an intracranial mass. Weight and body mass index were below the third percentile and he demonstrated loss of joint position and vibratory sense on examination. Laboratory studies revealed megaloblastic anaemia while an initial MRI of the brain showed no evidence of mass lesions or other abnormalities. A dietary history revealed the child subscribed to a restrictive vegan diet with little to no intake of animal products or other fortified foods. The child was diagnosed with presumed vitamin B12 deficiency and was treated with intramuscular B12 injections. Neurological symptoms resolved promptly within several days after starting therapy. This case underlines the importance of assessing nutritional status in the evaluation of neurological dysfunction in the pediatric patient. PMID:23536622

Crawford, John Ross; Say, Daphne



The absorption of free vitamin B 12 and R protein-bound vitamin B 12 in the diagnosis of pancreatic exocrine insufficiency in rats  

Microsoft Academic Search

Summary  Vitamin B12 (B12) absorption was studied in rats following biliopancreatic duct ligation. The absorption of free B12, as well as of hog R protein-bound B12, was markedly impaired after both intragastric and intraduodenal administration in these rats. The intraduodenal administration\\u000a of a mixture of pancreatic extract and sodium bicarbonate (NaHCO3) improved the absorption of both free and R protein-bound B12.

Wen-Liang Chen; Reiji Morishita; Tadashi Eguchi; Toshihide Kawai; Haruto Uchino



Biologically active vitamin B12 compounds in foods for preventing deficiency among vegetarians and elderly subjects.  


The usual dietary sources of vitamin B12 are animal-source based foods, including meat, milk, eggs, fish, and shellfish, although a few plant-based foods such as certain types of dried lavers (nori) and mushrooms contain substantial and considerable amounts of vitamin B12, respectively. Unexpectedly, detailed characterization of vitamin B12 compounds in foods reveals the presence of various corrinoids that are inactive in humans. The majority of edible blue-green algae (cyanobacteria) and certain edible shellfish predominately contain an inactive corrinoid known as pseudovitamin B12. Various factors affect the bioactivity of vitamin B12 in foods. For example, vitamin B12 is partially degraded and loses its biological activity during cooking and storage of foods. The intrinsic factor-mediated gastrointestinal absorption system in humans has evolved to selectively absorb active vitamin B12 from naturally occurring vitamin B12 compounds, including its degradation products and inactive corrinoids that are present in daily meal foods. The objective of this review is to present up-to-date information on various factors that can affect the bioactivity of vitamin B12 in foods. To prevent vitamin B12 deficiency in high-risk populations such as vegetarians and elderly subjects, it is necessary to identify plant-source foods that contain high levels of bioactive vitamin B12 and, in conjunction, to prepare the use of crystalline vitamin B12-fortified foods. PMID:23782218

Watanabe, Fumio; Yabuta, Yukinori; Tanioka, Yuri; Bito, Tomohiro



Uptake and transport of B12-conjugated nanoparticles in airway epithelium?  

PubMed Central

Non-invasive delivery of biotherapeutics, as an attractive alternative to injections, could potentially be achieved through the mucosal surfaces, utilizing nanoscale therapeutic carriers. However, nanoparticles do not readily cross the mucosal barriers, with the epithelium presenting a major barrier to their translocation. The transcytotic pathway of vitamin B12 has previously been shown to ‘ferry’ B12-decorated nanoparticles across intestinal epithelial (Caco-2) cells. However, such studies have not been reported for the airway epithelium. Furthermore, the presence in the airways of the cell machinery responsible for transepithelial trafficking of B12 is not widely reported. Using a combination of molecular biology and immunostaining techniques, our work demonstrates that the bronchial cell line, Calu-3, expresses the B12-intrinsic factor receptor, the transcobalamin II receptor and the transcobalamin II carrier protein. Importantly, the work showed that sub-200 nm model nanoparticles chemically conjugated to B12 were internalised and transported across the Calu-3 cell layers, with B12 conjugation not only enhancing cell uptake and transepithelial transport, but also influencing intracellular trafficking. Our work therefore demonstrates that the B12 endocytotic apparatus is not only present in this airway model, but also transports ligand-conjugated nanoparticles across polarised epithelial cells, indicating potential for B12-mediated delivery of nanoscale carriers of biotherapeutics across the airways.

Fowler, Robyn; Vllasaliu, Driton; Falcone, Franco H.; Garnett, Martin; Smith, Bryan; Horsley, Helen; Alexander, Cameron; Stolnik, Snow



Vitamin B-12 Supplementation during Pregnancy and Early Lactation Increases Maternal, Breast Milk, and Infant Measures of Vitamin B-12 Status.  


Pregnant women in resource-poor areas are at risk of multiple micronutrient deficiencies, and indicators of low vitamin B-12 status have been associated with adverse pregnancy outcomes, including anemia, low birth weight, and intrauterine growth retardation. To evaluate whether daily oral vitamin B-12 supplementation during pregnancy increases maternal and infant measures of vitamin B-12 status, we performed a randomized, placebo-controlled clinical trial. Pregnant women <14 wk of gestation in Bangalore, India, were randomly assigned to receive daily oral supplementation with vitamin B-12 (50 ?g) or placebo through 6 wk postpartum. All women were administered iron and folic acid supplements throughout pregnancy. One hundred eighty-three women were randomly assigned to receive vitamin B-12 and 183 to receive placebo. Compared with placebo recipients, vitamin B-12-supplemented women had significantly higher plasma vitamin B-12 concentrations at both the second (median vitamin B-12 concentration: 216 vs. 111 pmol/L, P < 0.001) and third (median: 184 vs. 105 pmol/L, P < 0.001) trimesters. At 6 wk postpartum, median breast milk vitamin B-12 concentration was 136 pmol/L in vitamin B-12-supplemented women vs. 87 pmol/L in the placebo group (P < 0.0005). Among vitamin B-12-supplemented women, the incidence of delivering an infant with intrauterine growth retardation was 33 of 131 (25%) vs. 43 of 125 (34%) in those administered placebo (P = 0.11). In a subset of infants tested at 6 wk of age, median plasma vitamin B-12 concentration was 199 pmol/L in those born to supplemented women vs. 139 pmol/L in the placebo group (P = 0.01). Infant plasma methylmalonic acid and homocysteine concentrations were significantly lower in the vitamin B-12 group as well. Oral supplementation of urban Indian women with vitamin B-12 throughout pregnancy and early lactation significantly increases vitamin B-12 status of mothers and infants. It is important to determine whether there are correlations between these findings and neurologic and metabolic functions. This trial was registered at as NCT00641862. PMID:24598885

Duggan, Christopher; Srinivasan, Krishnamachari; Thomas, Tinku; Samuel, Tinu; Rajendran, Ramya; Muthayya, Sumithra; Finkelstein, Julia L; Lukose, Ammu; Fawzi, Wafaie; Allen, Lindsay H; Bosch, Ronald J; Kurpad, Anura V



Maternal trace elements, vitamin B12, vitamin A, folic acid, and fetal malformations  

Microsoft Academic Search

The demonstrated teratogenicity of maternal zinc deficiency in rats has led to burgeoning interest in zinc and other trace elements as important factors in embryonic development. Levels of zinc, copper, manganese, magnesium, folic acid, vitamin B12 and vitamin A were evaluated at the beginning of pregnancy in the plasma of pregnant women who later delivered a malformed newborn. Fetal chromosomal

Claude Stoll; Béatrice Dott; Yves Alembik; Christian Koehl



Dietary folate and vitamin B 12 supplementation and consequent vitamin deposition in chicken eggs  

Microsoft Academic Search

We determined the effects of dietary supplementation with folate and vitamin B12 on lipid metabolism and the deposition of these vitamins in eggs of laying hens (age 64–72 weeks). Four levels of folate\\u000a (0, 0.5, 4 and 10 mg\\/kg) and three levels of vitamin B12 (0, 0.01 and 0.08 mg\\/kg) were added to the basal diet for 8 weeks in a 4?×?3 factorial completely

Chaiyapoom Bunchasak; Sompong Kachana



Vitamin B12 Deficiency Due to a Strictly Vegetarian Diet in Adolescence  

Microsoft Academic Search

A 14-year-old white girl suffered from severe neurologic disturbances caused by vitamin B12 deficiency, due to failure to provide vitamin B12 supplementation to a strictly vegetarian diet. The disturbances resolved completely following treatment with vatamin B12. Physicians should be alert to the necessity for vitamin B12 supplementation for strict vegetarians, who eat no meat, fish, eggs, or dairy products.

S. Ashkenazi; R. Weitz; I. Varsano; M. Mimouni



Vitamin B12 (cobalamin) deficiency in elderly patients  

PubMed Central

VITAMIN B12 OR COBALAMIN DEFICIENCY occurs frequently (> 20%) among elderly people, but it is often unrecognized because the clinical manifestations are subtle; they are also potentially serious, particularly from a neuropsychiatric and hematological perspective. Causes of the deficiency include, most frequently, food-cobalamin malabsorption syndrome (> 60% of all cases), pernicious anemia (15%–20% of all cases), insufficent dietary intake and malabsorption. Food-cobalamin malabsorption, which has only recently been identified as a significant cause of cobalamin deficiency among elderly people, is characterized by the inability to release cobalamin from food or a deficiency of intestinal cobalamin transport proteins or both. We review the epidemiology and causes of cobalamin deficiency in elderly people, with an emphasis on food-cobalamin malabsorption syndrome. We also review diagnostic and management strategies for cobalamin deficiency.

Andres, Emmanuel; Loukili, Noureddine Henoun; Noel, Esther; Kaltenbach, Georges; Abdelgheni, Maher Ben; Perrin, Anne Elisabeth; Noblet-Dick, Marie; Maloisel, Frederic; Schlienger, Jean-Louis; Blickle, Jean-Frederic



Holotranscobalamin, a marker of vitamin B-12 status: analytical aspects and clinical utility12345  

PubMed Central

Approximately one-quarter of circulating cobalamin (vitamin B-12) binds to transcobalamin (holoTC) and is thereby available for the cells of the body. For this reason, holoTC is also referred to as active vitamin B-12. HoloTC was suggested as an optimal marker of early vitamin B-12 deficiency >20 y ago. This suggestion led to the development of suitable assays for measurement of the compound and clinical studies that aimed to show the benefit of measurement of holoTC rather than of vitamin B-12. Today holoTC can be analyzed by 3 methods: direct measurement of the complex between transcobalamin and vitamin B-12, measurement of vitamin B-12 attached to transcobalamin, or measurement of the amount of transcobalamin saturated with vitamin B-12. These 3 methods give similar results, but direct measurement of holoTC complex is preferable in the clinical setting from a practical point of view. HoloTC measurement has proven useful for the identification of the few patients who suffer from transcobalamin deficiency. In addition, holoTC is part of the CobaSorb test and therefore useful for assessment of vitamin B-12 absorption. Clinical studies that compare the ability of holoTC and vitamin B-12 to identify individuals with vitamin B-12 deficiency (elevated concentration of methylmalonic acid) suggest that holoTC performs better than total vitamin B-12. To date, holoTC has not been used for population-based assessments of vitamin B-12 status, but we suggest that holoTC is a better marker than total vitamin B-12 for such studies.

Hoffmann-Lucke, Elke



The vitamin B12 content of human liver tissue obtained by aspiration biopsy  

PubMed Central

It is possible to estimate the vitamin B12 content of liver specimens obtained by needle biopsy. The liver B12 content is not related to the serum levels of vitamin B12, bilirubin, alkaline phosphatase, glutamic-oxaloacetic transaminase, or albumin. It is reduced in a number of pathological conditions of the liver and the reasons for this are discussed, as also are the factors determining the content of B12 in the normal liver.

Joske, R. A.



Enhanced anaerobic biotransformation of carbon tetrachloride with precursors of vitamin B 12 biosynthesis  

Microsoft Academic Search

Relatively low concentrations of Vitamin B12 are known to accelerate the anaerobic biotransformation of carbon tetrachloride (CT) and chloroform (CF). However, the addition of vitamin B12 for field-scale bioremediation is expected to be costly. The present study considered a strategy to generate vitamin B12 by addition of biosynthetic precursors. One of the precursors, porphobilinogen (PB) involved in the formation of

Claudia Guerrero-Barajas



Persistence of neurological damage induced by dietary vitamin B12 deficiency in infancy  

Microsoft Academic Search

A case is reported of a 14 month old boy with severe dietary vitamin B-12 deficiency caused by his mother’s vegan diet. Cinical, electroencephalography (EEG), and haematological findings are described. Cranial magnetic resonance imaging (MRI) showed severe frontal and frontoparietal cranial atrophy. Vitamin B-12 supplements led to a rapid improvement of haematological and neurological symptoms. Serum vitamin B-12 and urinary

Ursula von Schenck; Christine Bender-Götze; Berthold Koletzko



Imerslund-Gräsbeck syndrome (selective vitamin B12 malabsorption with proteinuria)  

Microsoft Academic Search

Imerslund-Gräsbeck syndrome (IGS) or selective vitamin B12 (cobalamin) malabsorption with proteinuria is a rare autosomal recessive disorder characterized by vitamin B12 deficiency commonly resulting in megaloblastic anemia, which is responsive to parenteral vitamin B12 therapy and appears in childhood. Other manifestations include failure to thrive and grow, infections and neurological damage. Mild proteinuria (with no signs of kidney disease) is

Ralph Gräsbeck



Association of aspirin use with vitamin B12 deficiency (results of the BACH study).  


We examined the prevalence of vitamin B(12) deficiency and its association with medication use and characteristics, including infection with Helicobacter pylori (H. pylori), in 255 patients hospitalized for cardiovascular disease. In almost half of the study population, vitamin B(12) deficiency was found; patients using acetylsalicylic acid were more frequently vitamin B(12) deficient in comparison to nonusers (p = 0.02). Fifty-one percent of the patients were infected with H. pylori, and fewer infected patients were vitamin B(12) deficient. PMID:15464695

van Oijen, Martijn G H; Laheij, Robert J F; Peters, Wilbert H M; Jansen, Jan B M J; Verheugt, Freek W A



Delirium as a result of vitamin B12 deficiency in a vegetarian female patient.  


Vitamin B12 deficiency can manifest with haematological, gastrointestinal and neuropsychiatric signs. The neuropsychiatric symptoms may be concurrent or precede the other symptoms. The reported case is a clinical case of delirium due to vitamin B12 deficiency in a female vegetarian patient. The patient was treated with vitamin B12 supplementation. Initially, it was difficult to diagnose this patient, who presented with delirium that could have been due to multiple causes. The finding underlines the importance of conducting a complete laboratory test panel for delirium, including the blood levels of vitamin B12. PMID:23859997

Mavrommati, K; Sentissi, O



Homocysteine, folate, vitamin B12 and vitamin B6 in patients receiving antiepileptic drug monotherapy  

Microsoft Academic Search

We hypothesized that elevated plasma homocysteine concentrations (hyperhomocysteinemia) exist in patients receiving antiepileptic drugs (AED), and a long-term administration of AED may result in an increased risk of occlusive vascular disease in these patients. A total of 62 patients who received AED monotherapy (phenytoin, lamotrigine, carbamazepine or valproate) participated in this study. Blood concentrations of homocysteine, folate, vitamin B-12 and

Tsunenobu Tamura; Kenji Aiso; Kelley E Johnston; Lori Black; Edward Faught



Vitamin B12 deficiency & levels of metabolites in an apparently normal urban south Indian elderly population  

PubMed Central

Background & objectives: There is no published literature on the extent of vitamin B12 deficiency in elderly Indians as determined by plasma vitamin B12 levels and methylmalonic acid (MMA) levels. Vitamin B12 deficiency is expected to be higher in elderly Indians due to vegetarianism, varied socio-economic strata and high prevalence of Helicobacter pylori infection. We therefore, studied the dietary habits of south Indian urban elderly population and measured vitamin B12, MMA red cell folate and homocysteine (Hcy) levels. Methods: Healthy elderly urban subjects (175, >60 yr) were recruited. Detailed history, physical examination and neurological assessment were carried out. Food Frequency Questionnaire (FFQ) for dietary analysis for daily intake of calories, vitamin B12, folate and detailed psychological assessment for cognitive functions was carried out. Blood samples were analyzed for routine haematology and biochemistry, vitamin B12, red cell folate, MMA and Hcy. Results: The mean age of the study population was 66.3 yr. Median values for daily dietary intake of vitamin B12 and folate were 2.4 and 349.2 ?g/day respectively. Sixty two (35%) participants consumed multivitamin supplements. Plasma vitamin B12 level and the dietary intake of vitamin B12 was significantly correlated (P=0.157). Plasma vitamin B12 and Hcy were inversely correlated (P= -0.509). Red cell folate was inversely correlated with Hcy (P= -0.550). Significant negative correlation was observed between plasma vitamin B12 and MMA in the entire study population (P= -0.220). Subjects consuming vitamin supplements (n=62) had significantly higher plasma vitamin B12 levels, lower MMA levels and lower Hcy levels. There was no significant correlation between plasma vitamin B12, MMA, Hcy and red cell folate and any of the 10 cognitive tests including Hindi Mental Status Examination (HMSE). Interpretation & conclusions: Our study is indicative of higher vitamin B12 (2.4 ?g/day) intakes in urban south Indian population. Thirty five per cent of the study population consumed multivitamin supplements and therefore, low plasma vitamin B12 levels were seen only in 16 per cent of the study subjects. However, MMA was elevated in 55 per cent and Hcy in 13 per cent of the subjects.

Shobha, Vineeta; Tarey, Subhash D.; Singh, Ramya G.; Shetty, Priya; Unni, Uma S.; Srinivasan, Krishnamachari; Kurpad, Anura V.



Vitamin B-12 and homocysteine status among vegetarians: a global perspective.  


Evidence exists that well-planned vegetarian diets provide numerous health benefits and are appropriate for all stages of the life cycle. It is also known that animal foods provide micronutrients that are nonexistent or available only in limited amounts in plant foods. Restriction or exclusion of all animal foods may therefore result in low intake of certain micronutrients such as vitamin B-12, thereby affecting vitamin B-12 status and elevating plasma homocysteine concentrations. Overall, the studies we reviewed showed reduced mean vitamin B-12 status and elevated mean homocysteine concentrations in vegetarians, particularly among vegans. Low vitamin B-12 intake may lead to decreased bioavailability and functional deficiency of cobalamin. Although early noticeable symptoms of vitamin B-12 deficiency are nonspecific (unusual fatigue, digestion problems, frequent upper respiratory infections), the best-known clinical manifestations of cobalamin malabsorption are hematologic (pernicious anemia) and neurologic symptoms. Hyperhomocysteinemia is associated with an increased risk of atherosclerosis and cardiovascular disease. Given these health concerns, vegetarians, particularly vegans, must be advised to carefully plan their diets, to monitor their plasma vitamin B-12 on a regular basis to facilitate early detection of low cobalamin status, and to use vitamin B-12-fortified foods or take vitamin B-12 supplements if necessary. PMID:19357223

Elmadfa, Ibrahim; Singer, Ingrid



Long term use of metformin leading to vitamin B 12 deficiency.  


Metformin is a commonly used oral hypoglycaemic agent worldwide. Gastrointestinal side effects and lactic acidosis related to metformin usage are commonly recognized. However, the associated vitamin B12 deficiency is less well known. We present a case of long term metformin use resulting in vitamin B12 deficiency. PMID:24674102

Tung, Moon Ley; Tan, Lip Kun



Loss of vitamin B(12) in fish (round herring) meats during various cooking treatments.  


The loss of vitamin B(12) in round herring meats during various cooking treatments was evaluated. Although amounts of vitamin B(12) were three times greater in the viscera (37.5 ± 10.6 µg/100 g fresh weight) than in the meats, about 73% of total vitamin B(12) found in the whole fish body (except for head and bones) were recovered in the meats (5.1 ± 1.0 µg of vitamin B(12)). The vitamin B(12) contents of the round herring's meats were significantly decreased up to ~62% during cooking by grilling, boiling, frying, steaming, and microwaving. There was, however, no loss of vitamin B(12) during vacuum-packed pouch cooking. Model experiment using hydroxocobalamin suggest that loss of vitamin B(12) is dependent on the degree of temperature and time used in conventional cooking, and is further affected by the concomitant ingredients of food. Retention of vitamin B(12) was not dependent on vacuum or temperature (or both) used in the vacuum-packed pouch cooking. PMID:22472286

Nishioka, Michiko; Kanosue, Fuki; Yabuta, Yukinori; Watanabe, Fumio



The master key effect of vitamin B12 in treatment of malignancy--a potential therapy?  


Vitamin B12 plays a functional role in a variety of organs and body systems and the list of these organs and body systems is growing. According to our working hypothesis ("Master Key Effect") vitamin B12 has some unique functions, which are still not accepted; vitamin B12 functions to keep body systems in balance, even under the stress of severe pathology. What is the explanation for elevation of cobalamin level in oncological patients? As yet I have not been able to find another explanation for high level of vitamin B12 in oncology patients other than that it is a compensatory mechanism. Perhaps following this body's "warning sign", we should start treatment with high doses of vitamin B12 to try to help the stabilization of normal function of the organs and systems. Laboratory researches should be continued to substantiate introduction of cobalamin as preliminary treatment of particular diseases. PMID:17640826

Volkov, Ilia



Vitamin B12 and ageing: current issues and interaction with folate.  


A compromised vitamin B12 status is common in older people despite dietary intakes that typically far exceed current recommendations. The maintenance of an optimal status of vitamin B12 is not only dependent on adequate dietary intake but more critically on effective absorption which diminishes with age. The measurement of vitamin B12 is complicated by the lack of a gold standard assay. There are a number of direct and functional indicators of vitamin B12 status; however, none of these are without limitations and should be used in combination. Vitamin B12 is of public health importance, not only because deficiency leads to megaloblastic anaemia and irreversible nerve damage, but also because emerging evidence links low B12 to an increased risk of a number of age-related diseases, including cardiovascular disease, cognitive dysfunction, dementia and osteoporosis. Furthermore, there are concerns relating to potential adverse effects for older adults with low vitamin B12 status of over-exposure to folic acid in countries where there is mandatory fortification of food with folic acid. The aim of this review is to examine the known and emerging issues related to vitamin B12 in ageing, its assessment and inter-relationship with folate. PMID:23592803

Hughes, Catherine F; Ward, Mary; Hoey, Leane; McNulty, Helene



Effect of folic acid and vitamin B 12 administration on phenytoin induced toxicity in rats  

Microsoft Academic Search

Folic acid and vitamin B12 are very important vitamins needed for normal cellular metabolic activities. The effects of folic acid and vitamin B12 on liver integrity of growing Wistar albino rats following therapeutic dose of phenytoin administration were investigated.\\u000a The activities of serum AST, ALT, ALP were investigated. Serum total protein level and lipid profile were also measured as\\u000a indices

Itemobong S. Ekaidem; Monday I. Akpanabiatu; Friday E. Uboh; Offiong U. Eka



Folate, Vitamin B6, and B12 Intakes in Relation to Risk of Stroke Among Men  

Microsoft Academic Search

Background and Purpose—Folate, vitamin B6, and B12 deficiency are related to elevated blood homocysteine level. However, the effects of intakes of these vitamins on risk of stroke are still uncertain. This study examines intakes of folate, vitamin B6, and B12 in relation to risk of ischemic and hemorrhagic stroke. Methods—We enrolled 43 732 men, aged 40 to 75 years, who

Ka He; Anwar Merchant; Eric B. Rimm; Bernard A. Rosner; Meir J. Stampfer; Walter C. Willett; Alberto Ascherio


Hyperhomocysteinemia in chronic alcoholism: relations to folic acid and vitamins b 6 and b 12 status  

Microsoft Academic Search

The objective of this review is to present and discuss the current perspectives of homocysteine and one carbon metabolism in chronic alcoholism. Chronic alcoholics frequently suffer from specific micronutrient deficiencies, including vitamins involved in one carbon metabolism, i.e., folate, vitamin B6 and vitamin B12. The possible link between homocysteine and alcoholism stems from the fact that homocysteine metabolism is closely

Mar??lia L Cravo; Maria E Camilo



Amniotic fluid folate, vitamin B12 and transcobalamins in neural tube defects.  


Levels of folate, vitamin B12, the vitamin B12 binding proteins, apotranscobalamin I, II and III (TC I, II and III) and the unsaturated vitamin B12 binding capacity (UBBC) were measured in mid-trimester amniotic fluids from normal pregnancies, and from those where the fetus had open spina bifida, anencephaly or omphalocoele, and where the fetus was normal but the mother had had a previous neural tube defect pregnancy. At 15-19 weeks' gestation, vitamin B12 levels were low in the fluids of all the types of abnormal fetuses, and also of normal fetuses where there had been a previous NTD sib. In contradistinction, TC I, II and III and UBBC levels were generally abnormally high in all these groups. Low vitamin B12 levels in the face of high carrier protein levels suggest deranged vitamin B12 production or transport. Since these abnormalities are present in fluids from normal sibs of NTD individuals as well as from those with midline lesions, an inherited defect is implied. We propose that at least part of the genetic predisposition to NTD, and possibly other midline defects, could reside in an abnormality connected with vitamin B12 production, transport or metabolism, and a mechanism is suggested. PMID:3048802

Gardiki-Kouidou, P; Seller, M J



Vitamin B12 absorption capacity in healthy children  

SciTech Connect

B12 absorption was investigated in 47 healthy children aged 7 months to 15.8 years (median 4.9 years). The patients had either recovered from giardiasis, the post-gastroenteritis syndrome, or had celiac disease in remission (treated with a gluten-free diet). The B12 absorption was measured by a double-isotope technique using /sup 57/CoB12 and /sup 51/CrCl/sub 3/, the latter being the inabsorbable marker. The radiation dose was minimal. The results were presented as fractional absorption of B12 (FAB12). Within the different age groups, the absorption test was performed by means of the following oral amounts of B12: 0- less than 1 year, 0.5 microgram; 1-3 years: 1.7 micrograms, 4-6 years, 2.5 micrograms; 7-10 years; 3.3 micrograms; and 11-15 years, 4.5 micrograms. When using these oral amounts of B12, the medians (and ranges) of FAB12 were found to be: 1-3 years (n = 18), 37% (16-80%); 4-6 years (n = 10), 27% (19-40%); 7-10 years (n = 9), 32% (21-44%); and 11-15 years (n = 8), 27% (19-59%). The FAB12 in two children aged 7 and 11 months was 31% and 32%, respectively. These results may be interpretated as reference values for B12 absorption in children. Further absorption tests were performed in seven children representing the four age groups from 1 to 15 years. When a high oral amount of B12 was given (i.e., three times the saturation dose), the FAB12 ranged from 0 to 20% (median 9%), whereas a low amount (i.e., one-ninth of the saturation dose) produced fractional absorptions from 65 to 82% (median 74%).

Hjelt, K.; Krasilnikoff, P.A.



Most harmful algal bloom species are vitamin B1 and B12 auxotrophs  

PubMed Central

Eutrophication can play a central role in promoting harmful algal blooms (HABs), and therefore many HAB studies to date have focused on macronutrients (N, P, Si). Although a majority of algal species require exogenous B vitamins (i.e., auxotrophic for B vitamins), the possible importance of organic micronutrients such as B vitamins (B1, B7, B12) in regulating HABs has rarely been considered. Prior investigations of vitamins and algae have examined a relatively small number of dinoflagellates (n = 26) and a paucity of HAB species (n = 4). In the present study, the vitamin B1, B7, and B12 requirements of 41 strains of 27 HAB species (19 dinoflagellates) were investigated. All but one species (two strains) of harmful algae surveyed required vitamin B12, 20 of 27 species required B1, and 10 of 27 species required B7, all proportions higher than the previously reported for non-HAB species. Half-saturation (Ks) constants of several HAB species for B1 and B12 were higher than those previously reported for other phytoplankton and similar to vitamin concentrations reported in estuaries. Cellular quotas for vitamins suggest that, in some cases, HAB demands for vitamins may exhaust standing stocks of vitamins in hours to days. The sum of these findings demonstrates the potentially significant ecological role of B-vitamins in regulating the dynamics of HABs.

Tang, Ying Zhong; Koch, Florian; Gobler, Christopher J.



The effects of vitamins C and B12 on human nasal ciliary beat frequency  

PubMed Central

Background This study was designed to investigate the effects of the vitamins C and B12 on the regulation of human nasal ciliary beat frequency (CBF). Methods Human nasal mucosa was removed endoscopically and nasal ciliated cell culture was established. Changes of CBF in response to different concentrations of vitamin C or vitamin B12 were quantified by using high-speed (240 frames per second) digital microscopy combined with a beat-by-beat CBF analysis. Results At the concentrations of 0.01% and 0.10%, vitamin C induced an initial increase, followed by a gradual decrease of CBF to the baseline level, while 1.00% vitamin C induced a reversible decrease of CBF. Vitamin B12, at the concentrations of 0.01% and 0.10%, did not influence CBF during the 20-min observation period, while a 1.00% vitamin B12 treatment caused a time-dependent but reversible decrease of CBF. Conclusions Treatment with vitamin C or vitamin B12 caused a concentration-dependent but reversible decrease of CBF in cultured human nasal epithelial cells. Therefore, it is necessary to choose a concentration that is safe, effective, and non-ciliotoxic when applying these drugs topically in the nasal cavity.



Vitamin B12 could be a "master key" in the regulation of multiple pathological processes.  


Multifunctional systems must maintain homeostasis. Man is an ideal example of a system that constantly aspires to attain optimal regulation, even under the stress of severe disease. We assume that there are universal, interchangeable (as required) biologically active substances that regulate the system and try to keep it in balance. We propose that one of these substances is vitamin B12. Why vitamin B12? The list of organs and body systems in which vitamin B12 plays a functional role is constantly being added to. Vitamin B12 affects the normal growth of children, the peripheral and central nervous systems, bone marrow, skin, mucous membranes, bones, and vessels. It is possible that even when the serum cobalamin level is normal, treatment with vitamin B12 could correct defects caused by other biologically active substances. We call this phenomenon the "Master Key" effect. We suggest that this "Master Key" concept can be tested by treating diseases, such as recurrent stomatitis, various forms of hyperpigmentation, trophic ulcers, and burns, with vitamin B12, even if the B12 serum level is normal. PMID:16641529

Volkov, Ilia; Press, Yan; Rudoy, Inna



Folate and vitamin B12 status of a multiethnic adult population.  

PubMed Central

BACKGROUND: Folic acid and vitamin B12 are of particular interest for their diverse biological functions and preventive roles in many prevalent chronic diseases. However, ethnic differences on the status of these vitamins have not been investigated among multiethnic adult college students. METHODS: A cross-sectional study (n = 177) was conducted to determine the dietary intakes and levels of serum concentrations of folate and vitamin B12 among triethnic college students-non-Hispanic white, Hispanic and non-Hispanic black. Dietary intake was assessed using a validated food frequency questionnaire, and serum was analyzed for folate and vitamin B12 using standardized methods. RESULTS: Mean intakes of both vitamins without supplementation was higher (P < 0.05) among non-Hispanic white males than females, and non-Hispanic white and non-Hispanic black males and females. Non-Hispanic white females had a significantly lower mean dietary intake of vitamin B12 than the females of other ethnic groups (P < 0.01). There was a positive correlation between B12 intake and serum concentrations. More than 52% of the females did not meet the required folate intake of 400 microg/day. CONCLUSIONS: The data suggest that there was no difference in overall mean intake of folate and vitamin B12 or serum concentrations in regard to gender or ethnicity. One-fourth of the female subjects failed to meet the recommended folate intake when supplement was excluded.

Nath, Subrata D.; Koutoubi, Samer; Huffman, Fatma G.



Pigmentation in vitamin B12 deficiency masquerading Addison's pigmentation: A rare presentation.  


A 35-year-female presented with generalized weakness, weight loss, and progressive pigmentation was worked up for suspicion of Addisons disease. On examination hyper pigmentation was noted on both palmar and dorsal aspect of hands involving knuckles, creases, feet, tongue, oral mucosa and gluteal region. There was no evidence of hypocortisolemia as initially suspected, and literature search revealed a possibility of vitamin B12 deficiency. She had megaloblastic anemia with a low serum vitamin B12, mostly due to poor dietary intake. Her hyper pigmentation resolved with vitamin B12 supplementation. Skin biopsy showed increased pigmentation at stratum spinosum and basal-layer. The mechanism of hyper pigmentation in vitamin B12 deficiency was due to an increase in melanin synthesis. PMID:24251178

Agrawala, Ritesh Kumar; Sahoo, Srikanta Kumar; Choudhury, Arun Kumar; Mohanty, Binoy Kumar; Baliarsinha, Anoj Kumar



Cerebral atrophy in a vitamin B12-deficient infant of a vegetarian mother.  


In developed countries, vitamin B12 (cobalamin) deficiency usually occurs in children, exclusively breastfed ones whose mothers are vegetarian, causing low body stores of vitamin B12. The haematologic manifestation of vitamin B12 deficiency is pernicious anaemia. It is a megaloblastic anaemia with high mean corpuscular volume and typical morphological features, such as hyperlobulation of the nuclei of the granulocytes. In advanced cases, neutropaenia and thrombocytopaenia can occur, simulating aplastic anaemia or leukaemia. In addition to haematological symptoms, infants may experience weakness, fatigue, failure to thrive, and irritability. Other common findings include pallor, glossitis, vomiting, diarrhoea, and icterus. Neurological symptoms may affect the central nervous system and, in severe cases, rarely cause brain atrophy. Here, we report an interesting case, a 12-month old infant, who was admitted with neurological symptoms and diagnosed with vitamin B12 deficiency. PMID:25076673

Kocaoglu, Celebi; Akin, Fatih; Caksen, Hüseyin; Böke, Saltuk Bu?ra; Arslan, Sükrü; Aygün, Serhat



Improved large-scale production of vitamin B12 by Pseudomonas denitrificans with betaine feeding.  


The strategy of betaine control for vitamin B12 large-scale fermentation by Pseudomonas denitrificans was investigated in this paper. The results obtained in shake-flask experiments demonstrated that betaine could greatly stimulate vitamin B12 biosynthesis but had an inhibition to cell growth. Based on the influence of betaine on the fermentation of P. denitrificans, betaine feeding was a beneficial strategy to solve the inconsistency between cell growth and vitamin B12 production. As a result, an effective and economical strategy of betaine feeding was established for vitamin B12 fermentation in 120-m3 fermenter, in which betaine was continuously fed to maintain betaine concentration of the broth at the range of 5-7g/l during 50-140h of fermentation. PMID:18440227

Li, Kun-Tai; Liu, Dong-Hong; Li, Yong-Liang; Chu, Ju; Wang, Yong-Hong; Zhuang, Ying-Ping; Zhang, Si-Liang



Association of Vitamin B12 Deficiency and Metformin Use in Patients with Type 2 Diabetes  

PubMed Central

We evaluated the prevalence of vitamin B12 deficiency and associated factors in type 2 diabetes patients using metformin. A total of 799 type 2 diabetes patients using metformin was enrolled. Vitamin B12 and folate levels were quantified by chemiluminescent enzyme immunoassay. Vitamin B12 deficiency was defined as vitamin B12 ? 300 pg/mL without folate deficiency (folate > 4 ng/mL). The prevalence of vitamin B12 deficiency in metformin-treated type 2 diabetes patients was 9.5% (n = 76), and the mean vitamin B12 level was 662.5 ± 246.7 pg/mL. Vitamin B12 deficient patients had longer duration of metformin use (P < 0.001) and higher daily metformin dose (P < 0.001) than non-deficient patients. Compared with daily metformin dose of ? 1,000 mg, the adjusted odds ratio for 1,000-2,000 mg, and ? 2,000 mg were 2.52 (95% CI, 1.27-4.99, P = 0.008) and 3.80 (95% CI, 1.82-7.92, P < 0.001). Compared with metformin use of < 4 yr, the adjusted odds ratios for 4-10 yr, and ? 10 yr were 4.65 (95% CI, 2.36-9.16, P < 0.001) and 9.21 (95% CI, 3.38-25.11, P < 0.001), respectively. In conclusion, our study indicates that patients with type 2 diabetes treated with metformin should be screened for vitamin B12 deficiency, especially at higher dosages (> 1,000 mg) and longer durations (? 4 yr) of treatment. Graphical Abstract

Ahn, Yu-Bae; Ko, Seung-Hyun



A water channel in the core of the vitamin B 12 RNA aptamer  

Microsoft Academic Search

Background: The 3.0 Å crystal structure of the vitamin B12 RNA aptamer revealed an unusual tertiary structure that is rich in novel RNA structural motifs. Important details of the interactions that stabilize noncanonical base pairing and the role of solvent in the structure were not apparent owing to the limited resolution.Results: The structure of the vitamin B12 RNA aptamer in

Django Sussman; Charles Wilson



Brief report: childhood disintegrative disorder as a likely manifestation of vitamin B12 deficiency.  


Childhood disintegrative disorder is a rare disorder, characterized by regression of acquired skills after a period of normal development. The case of childhood disintegrative disorder presented here was found to have vitamin B12 deficiency and hyperhomocysteinemia on extensive evaluation to find a probable cause for regression. This case illustrates the need for a thorough evaluation of all cases of childhood disintegrative disorder so that treatable causes of regression, like vitamin B12 deficiency, are not missed. PMID:23334842

Malhotra, Savita; Subodh, B N; Parakh, Preeti; Lahariya, Sanjay



Alteration of bile acid metabolism and vitamin-B 12 -absorption in diabetics on biguanides  

Microsoft Academic Search

Summary  Since vitamin B12malabsorption has been described in diabetics on biguanides and inhibition of bile acid absorption found in rat ileum the effect of treatment with different biguanides (phenformin, buformin, metformin) on bile acid metabolism and vitamin B12 absorption was assessed in maturity onset diabetics. Biguanides did not alter faecal weight or faecal fat excretion, but they decreased faecal bile acid

W. F. Caspary; I. Zavada; W. Reimold; U. Deuticke; D. Emrich; B. Willms



Improved large-scale production of vitamin B 12 by Pseudomonas denitrificans with betaine feeding  

Microsoft Academic Search

The strategy of betaine control for vitamin B12 large-scale fermentation by Pseudomonas denitrificans was investigated in this paper. The results obtained in shake-flask experiments demonstrated that betaine could greatly stimulate vitamin B12 biosynthesis but had an inhibition to cell growth. Based on the influence of betaine on the fermentation of P. denitrificans, betaine feeding was a beneficial strategy to solve

Kun-Tai Li; Dong-Hong Liu; Yong-Liang Li; Ju Chu; Yong-Hong Wang; Ying-Ping Zhuang; Si-Liang Zhang



Influence of Zn 2+ , Co 2+ and dimethylbenzimidazole on vitamin B 12 biosynthesis by Pseudomonas denitrificans  

Microsoft Academic Search

Previous research has confirmed that cobalt ion and dimethylbenzimidazole (DMBI) are the precursors of vitamin B12 biosynthesis, and porphobilinogen synthase (PBG synthase) is a zinc-requiring enzyme. In this paper, the effects of Zn2+, Co2+ and DMBI on vitamin B12 production by Pseudomonas denitrificans in shake flasks were studied. Present experimental results demonstrated that the addition of the above mentioned three

Kun-Tai Li; Dong-Hong Liu; Ying-Ping Zhuang; Yong-Hong Wang; Ju Chu; Si-Liang Zhang



Vitamin B12 Synthesis and Salvage Pathways Were Acquired by Horizontal Gene Transfer to the Thermotogales  

PubMed Central

The availability of genome sequences of Thermotogales species from across the order allows an examination of the evolutionary origins of phenotypic characteristics in this lineage. Several studies have shown that the Thermotogales have acquired large numbers of genes from distantly related lineages, particularly Firmicutes and Archaea. Here, we report the finding that some Thermotogales acquired the ability to synthesize vitamin B12 by acquiring the requisite genes from these distant lineages. Thermosipho species, uniquely among the Thermotogales, contain genes that encode the means to synthesize vitamin B12 de novo from glutamate. These genes are split into two gene clusters: the corrinoid synthesis gene cluster, that is unique to the Thermosipho and the cobinamide salvage gene cluster. The corrinoid synthesis cluster was acquired from the Firmicutes lineage, whereas the salvage pathway is an amalgam of bacteria- and archaea-derived proteins. The cobinamide salvage gene cluster has a patchy distribution among Thermotogales species, and ancestral state reconstruction suggests that this pathway was present in the common Thermotogales ancestor. We show that Thermosipho africanus can grow in the absence of vitamin B12, so its de novo pathway is functional. We detected vitamin B12 in the extracts of T. africanus cells to verify the synthetic pathway. Genes in T. africanus with apparent B12 riboswitches were found to be down-regulated in the presence of vitamin B12 consistent with their roles in B12 synthesis and cobinamide salvage.

Swithers, Kristen S.; Petrus, Amanda K.; Secinaro, Michael A.; Nesb?, Camilla L.; Gogarten, J. Peter; Noll, Kenneth M.; Butzin, Nicholas C.



Specificity of the Stimulatory Effect of Betaine on the Vitamin B12 Fermentation  

Microsoft Academic Search

METHYL donors such as betaine and choline are known to stimulate production of vitamin B12 by certain microorganisms1. Ansbacher and Hill2 reported that of the crude microbial processes available in 1949, the best were characterized by disappearance of choline from the medium. Miller and Putter of these laboratories (unpublished) discovered that betaine and choline stimulate B12 production by Pseudomonas denitrificans;

Arnold L. Demain; Horace J. Daniels; Lubove Schnable; Raymond F. White



Evaluation of vitamin B12 effects on DNA damage induced by paclitaxel.  


Abstract Paclitaxel (PAC) is an anticancer drug that has been shown to generate free radicals leading to irreversible cell injury. Vitamin B12 has antioxidative properties and can protect DNA from free radicals. In this study, we examined the possible genotoxic effect of PAC on DNA as well as the possible protective effect of vitamin B12 on DNA damage induced by paclitaxel. Sister chromatid exchanges (SCEs), chromosomal aberrations (CAs) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were measured in cultured human blood lymphocytes treated with PAC (10?µM) and/or vitamin B12 (2.7?mg/mL). Our results showed that PAC significantly increased the frequencies of SCEs (p?vitamin B12. In addition, we showed that PAC induced an increase in 8-OHdG, a marker of oxidative DNA damage, and that this increase was prevented by vitamin B12. Vitamin B12 seems to protect against genotoxicity induced by PAC in human blood lymphocytes. PMID:24215581

Alzoubi, Karem; Khabour, Omar; Khader, Manal; Mhaidat, Nizar; Al-Azzam, Sayer



Association of Vitamin B12 Deficiency with Fatigue and Depression after Lacunar Stroke  

PubMed Central

Background In lacunar stroke patients vitamin B12 deficiency is often found and a relationship with the degree of periventricular white matter lesions (pWMLs) is suggested. Given the known relationships between WMLs and depression and between depression and fatigue after stroke, we studied both depression and fatigue in lacunar stroke patients with and without vitamin B12 deficiency. Methods In 40 first-ever lacunar stroke patients vitamin B12 levels were determined and self-report questionnaires for fatigue and depression were completed three months after stroke. Results Lacunar stroke patients with vitamin B12 deficiency (N?=?13) reported significantly more fatigue (90.7 versus 59.4; p?=?.001) and depressive symptoms (6.62 versus 3.89; p<.05) than those without (N?=?27). In regression analyses, vitamin B12 deficiency was significantly and independently associated with the presence of severe fatigue and clinically significant depression. Conclusions Our preliminary results suggest a relationship between vitamin B12 deficiency and increased levels of fatigue and depression in lacunar stroke patients. If these findings could be replicated in a larger and general stroke sample, this would open treatment options and may improve quality of life after stroke.

Huijts, Marjolein; Duits, Annelien; Staals, Julie; van Oostenbrugge, Robert J.



Absence of signs of vitamin B12--nitrous oxide interaction in operating theatre personnel.  


Inactivation of vitamin B12 by nitrous oxide leads to megaloblastic haematopoiesis. Peripheral blood counts and films, serum vitamin B12 and plasma and erythrocyte folate concentrations were studied in eight anaesthetists and seven internists to find if the interaction is an occupational health hazard to operating theatre personnel chronically exposed to trace concentrations of nitrous oxide. In addition, blood counts were studied in two retrospective materials of 118 operating theatre nurses working in scavenged operating theatres and in ten subjects working in unscavenged theatres. No definite signs of B12-nitrous oxide interaction could be observed in the peripheral blood samples from these persons. PMID:6711254

Salo, M; Rajamäki, A; Nikoskelainen, J



Requirements of Cultured Mammalian Cells for Vitamin B12 and Biotin.  

National Technical Information Service (NTIS)

Eagle reported in 1955 and 1957 that eight vitamins were essential for the growth of most mammalian cells in culture. No evidence for requirement of vitamin B12 or of biotin was presented. Sanford and co-workers in 1963 and 1964 reported evidence for requ...

K. Higuchi



Vitamin B12 Cream Containing Avocado Oil in the Therapy of Plaque Psoriasis  

Microsoft Academic Search

Background: There are already many effective topical therapies available for use in the treatment of chronic plaque psoriasis. Unfortunately, these treatments are often associated with a rather significant risk of undesirable effects. Objective and Methods: In this randomized, prospective clinical trial, the effects of the vitamin D3 analog calcipotriol were evaluated against those of a recently developed vitamin B12 cream

Markus Stücker; Ulrike Memmel; Matthias Hoffmann; Joachim Hartung; Peter Altmeyer



Effect of oral vitamin B12 with or without folic acid on cognitive function in older people with mild vitamin B12 deficiency: a randomized, placebo-controlled trial1-3  

Microsoft Academic Search

Background:Vitamin B-12 deficiency is associated with cognitive impairment in older people. However, evidence from randomized trials of the effects of vitamin B-12 supplementation on cognitive function is limited and inconclusive. Objective: The objective was to investigate whether daily supple- mentation with high doses of oral vitamin B-12 alone or in combi- nationwithfolicacidhasanybeneficialeffectsoncognitivefunction in persons aged 70 y with mild vitamin

Simone J Eussen; Lisette C de Groot; Liesbeth W Joosten; Rubia J Bloo; Robert Clarke; Per M Ueland; Jörn Schneede; Henk J Blom; Willibrord H Hoefnagels; Wija A van Staveren


Influence of vitamin B 12 and light on the formation of chlorosomes in green- and brown-colored Chlorobium species  

Microsoft Academic Search

The specific Bchl a and c content of the vitamin B12-dependent Chlorobium limicola strain 1230 decreased strongly under vitamin B12 limitation. In comparison to a regularly grown culture (20 µg vitamin B12\\/l) the specific Bchl c content of a B12-limited culture was reduced to 20% and the specific Bchl a content to 42%. By ultrathin sections it could be clearly

Sabine Fuhrmann; Jiirg Overmann; Norbert Pfennig; Ulrich Fischer



Interaction of Nutrition and Infection: Effect of Vitamin B12 Deficiency on Resistance to Trypanosoma Lewisi  

PubMed Central

A metabolic imbalance technique was employed to study vitamin B12 deficiency in rats infected with Trypanosoma lewisi. Throughout the observational period, animals on the deficient diet had lowered serum vitamin B12 levels compared with complete and pair-fed animals. The decline in the level of the vitamin, ten days after the initiation of the experiment, continued progressively until the termination of the study. Body weight gains and food consumption in rats on complete, vitamin B12-deficient, or pair-fed diets and inoculated with T lewisi showed significant increase over inoculated controls. The rates of body weight and food consumption in vitamin B12-deficient animals were significantly less than that of the adequately fed animals. The indices of lowered resistance to infection in the vitamin B12-deficient rats were manifoid. Deficient rats suffered earlier and higher parasitemia followed by persistent infection. The delay in the synthesis of the reproductive inhibiting antibody (ablastin) resulted in prolonged variability in the length of the trypomastigotes. Severe depression in the primary and secondary antibody responses (IgG and IgM) to in vivo immunization of sheep erythrocytes was also observed in the deficient animals. In comparison, the level of IgG antibody decreased approximately one fifth the control values.

Thomaskutty, K.G.; Lee, C.M.



Effect of Amino Acid Availability on Vitamin B12 Production in Lactobacillus reuteri? †  

PubMed Central

Recent functional genomics and genome-scale modeling approaches indicated that B12 production in Lactobacillus reuteri could be improved by optimization of the medium. Here we show that a series of systematic single-amino-acid omissions could significantly modulate the production of B12 from nearly undetectable levels (with omission of isoleucine) to levels 20-fold higher than the levels previously reported (with omission of cysteine). Using cDNA microarray experiments, we analyzed the transcriptional response of L. reuteri to medium lacking cysteine. The results supported the observed high level of B12 production and provided new avenues for future improvement of production of vitamin B12.

Santos, Filipe; Teusink, Bas; Molenaar, Douwe; van Heck, Maurice; Wels, Michiel; Sieuwerts, Sander; de Vos, Willem M.; Hugenholtz, Jeroen



[Surface-enhanced raman spectroscopy study of vitamin B12 on copper electrode].  


The vitamin B12 molecule has long fascinated chemists because of its exclusive complex structure and unusual reactivities in biological systems. In order to achieve a better understanding of the structural attribute of the Vitamin B12 molecule when it interacted with metal, in the present paper, the vitamin B12 molecules adsorbed on variation of copper electrode potential from 0 to -1.0 V was studied by surface-enhanced Raman spectroscopy (SERS). An excellent SERS substrate was obtained with insitu electrochemical oxidation-reduction cycle (ORC), and its surface roughness was characterized by atomic force microscope (AFM). Assignments of Raman peaks observed by normal Raman spectrum (NRS) and SERS spectra of vitamin B12 molecule were given based on previous literatures. It was found that the potential-dependent relative intensity changed in SERS spectra which depended on the vitamin B12 molecular orientation with respect to the copper surface according to the surface selection rule (SSR). It was concluded that the corrin ring was adsorbed in tilt form on copper surface and the Co-CN group was farther away from the copper surface at higher potentials. With the decrease in potential, the tilt angle between the corrin ring and copper surface became smaller, then the Co-N group and 5,6 dimethylbenzimidazole group got close to the copper surface. The results offered an important structural attribute of vitamin B12 molecule when it interacted with copper electrode for the first time, and supplied a meaningful reference for the electrochemical bioactivity of the vitamin B12 molecule. PMID:24369644

Wang, Bo; Chang, Da-hu; Lu, Gang; Wang, Tian-hu; Zhang, Zhen-long; Mo, Yu-jun



Imerslund-Gr?sbeck syndrome (selective vitamin B12 malabsorption with proteinuria)  

PubMed Central

Imerslund-Gräsbeck syndrome (IGS) or selective vitamin B12 (cobalamin) malabsorption with proteinuria is a rare autosomal recessive disorder characterized by vitamin B12 deficiency commonly resulting in megaloblastic anemia, which is responsive to parenteral vitamin B12 therapy and appears in childhood. Other manifestations include failure to thrive and grow, infections and neurological damage. Mild proteinuria (with no signs of kidney disease) is present in about half of the patients. Anatomical anomalies in the urinary tract were observed in some Norwegian patients. Vitamin B12 absorption tests show low absorption, not corrected by administration of intrinsic factor. The symptoms appear from 4 months (not immediately after birth as in transcobalamin deficiency) up to several years after birth. The syndrome was first described in Finland and Norway where the prevalence is about 1:200,000. The cause is a defect in the receptor of the vitamin B12-intrinsic factor complex of the ileal enterocyte. In most cases, the molecular basis of the selective malabsorption and proteinuria involves a mutation in one of two genes, cubilin (CUBN) on chromosome 10 or amnionless (AMN) on chromosome 14. Both proteins are components of the intestinal receptor for the vitamin B12-intrinsic factor complex and the receptor mediating the tubular reabsorption of protein from the primary urine. Management includes life-long vitamin B12 injections, and with this regimen, the patients stay healthy for decades. However, the proteinuria persists. In diagnosing this disease, it is important to be aware that cobalamin deficiency affects enterocyte function; therefore, all tests suggesting general and cobalamin malabsorption should be repeated after abolishment of the deficiency.

Grasbeck, Ralph



Efficacy of folate and vitamin B12 in lowering homocysteine concentrations in hemodialysis patients.  


To evaluate the efficacy of supplementation with high dose folic acid with and without vitamin B 12 in lowering plasma total homocysteine (tHcy) concentrations in hemodialysis (HD) patients, we studied 36 HD patients randomized into four groups according to the received therapeutic regimen: group I (only folic acid (FA), 5 mg/day), group II (FA, 5 mg/day + vitamin B 12 , 1 mg/day) group III (only FA, 15 mg/day), group IV (FA, 15 mg/day, vitamin B 12 , 1 mg/day) for a period of 8 weeks. Plasma tHcy and serum FA and vitamin B 12 levels were measured at baseline and after the supplementation period. Dietary intakes were assessed during the study period. At baseline, 27.8% of the patients had normal levels of tHcy and 72.2% had hyperhomocysteinemia. After supplementation, plasma tHcy increased by 1.35% in group I and decreased by 6.99%, 14.54% and 30.09% in groups II, III and IV respectively, which was only significant in group IV (P= 0.014). The patients did not show any significant changes in serum folic acid, but a significant change in serum vitamin B 12 in group IV (P= 0.006). Percentage of patients reaching normal levels of plasma tHcy was 5.6 fold higher in group IV than in the reference group (group I). No correlations were found between changes of plasma tHcy levels and dietary intakes. We conclude that oral supplementation with 15 mg/day folic acid together with 1 mg/day of vitamin B 12 is effective in reducing tHcy levels in HD patients. These supplements also have a desirable effect on serum folic acid and vitamin B12. PMID:19736473

Azadibakhsh, Nassim; Hosseini, Rahebeh Shaker; Atabak, Shahnaz; Nateghiyan, Navid; Golestan, Banafsheh; Rad, Anahita Hooshyar



Homocysteine, vitamin B12, serum and erythrocyte folate in peritoneal dialysis patients.  


Plasma homocysteine (tHcy) is an important risk factor for atherosclerosis in dialysis patients. Few data were reported on the prevalence and severity of hyperhomocysteinemia in peritoneal dialysis (PD) patients. In addition, little attention was paid to the search of factors possibly involved in the pathogenesis of hyperhomocysteinemia in these patients. A cross-sectional study was performed in 107 stable PD patients. None of them was given folate or vitamin B12 supplementation before or during the study. Plasma tHcy, serum vitamin B12, serum and erythrocyte folate were measured by immunoenzymatic methods. Genetic analysis of the methylentetrahydrofolate-reductase thermolabile mutation (tMTHFR) was performed in 61 patients. 97% of patients had tHcy levels higher than normal. tHcy was not different between men and women, patients with or without malnutrition, with or without clinically evident atherosclerotic vasculopathy, with or without anemia. tHcy levels were significantly higher in homozygotes for the tMTHFR mutation than in patients carrying the wild type form. Significant univariate correlation was found between hyperhomocysteinemia and time since the start of dialysis, serum and erythrocyte folate and vitamin B12. The best fitted model equation was log tHcy = 108.53 + 0.1606 (duration of dialysis) -1.1053 (s-F) -0.7980 (age) 0.0215 (vitamin B12). Our results agree with those reported by other authors in hemodialysis patients. Despite the large number of PD patients with normal serum vitamin B12 and folate status, the relation between tHcy and vitamin B12 or folate suggests that the supplementation of these vitamins could be useful irrespective of their serum levels, especially in younger patients or in those treated for a long period of time with peritoneal dialysis. PMID:11334318

De Vecchi, A F; Bamonti-Catena, F; Finazzi, S; Patrosso, C; Taioli, E; Novembrino, C; Colucci, P; Lando, G; De Franceschi, M; Marocchi, A; Maiolo, A T



Inhibition of vitamin B12 metabolism by OH-cobalamin c-lactam in rat oligodendrocytes in culture: a model for studying neuropathy due to vitamin B12 deficiency.  


Vitamin B12 is implicated in methylation processes. Myelin basic protein is methylated on one arginine group. A defect in methylation could produce an unstable protein, leading to neurological disorders. In order to study myelin basic protein, we have developed the cultures of newborn rat oligodendrocytes in vitamin B12-depleted medium. As these cells do not grow without serum, vitamin B12 is always present. We overcame this problem by using OH-cobalamin c-lactam, an antagonist of B12. To ensure that the system was vitamin B12 deficient, we measured the concentrations of homocysteine and methylmalonic acid whose accumulations reflect a vitamin B12 deficiency. Methylmalonic acid was measured by mass spectrometry and homocysteine by HPLC. We obtained a powerful model for studying the influence of B12 deficiency on the synthesis of myelin compounds. PMID:10889340

Sponne, I E; Gaire, D; Stabler, S P; Droesch, S; Barbé, F M; Allen, R H; Lambert, D A; Nicolas, J P



[Neurological disorders related to vitamin B12 deficiency in prisons in Guinea: a 22-case study].  


Neurological disorders related to vitamin B12 deficiency are common in prisons of tropical Africa. We collected 22 cases (20 men and 2 women). They all showed vitamin B12 deficiency associated with neurological signs that were represented by sclerosis combined with bone marrow (n = 9), peripheral neuropathy (n = 6), cerebellar syndrome (n = 2), a pyramidal syndrome of the lower limbs (n = 4) and optic neuropathy (n = 1). Laboratory tests showed a mean hemoglobin concentration of 7.2 ± 1.5 g/dl, mean 104 ± 28 fl, macrocytic anemia in 10 patients. Biermer's disease was identified in 9 patients, 3 patients showed the syndrome of non dissociation of vitamin B12, a gastrectomy in 2 patients and no etiology was identified in 8 patients. PMID:23793871

Cisse, F A; Bah, H; Konate, F; Camara, N; Camara, M I; Conde, K; Kassory, I F B; Sanogo, A; Diakhate, I; Cisse, A



Recent advances in microbial production of ?-aminolevulinic acid and vitamin B12.  


?-aminolevulinate (ALA) is an important intermediate involved in tetrapyrrole synthesis (precursor for vitamin B12, chlorophyll and heme) in vivo. It has been widely applied in agriculture and medicine. On account of many disadvantages of its chemical synthesis, microbial production of ALA has been received much attention as an alternative because of less expensive raw materials, low pollution, and high productivity. Vitamin B12, one of ALA derivatives, which plays a vital role in prevention of anaemia has also attracted intensive works. In this review, recent advances on the production of ALA and vitamin B12 with novel approaches such as whole-cell enzyme-transformation and metabolic engineering are described. Furthermore, the direction for future research and perspective are also summarized. PMID:22537876

Kang, Zhen; Zhang, Junli; Zhou, Jingwen; Qi, Qingsheng; Du, Guocheng; Chen, Jian



Bone marrow cells from vitamin B12- and folate-deficient patients misincorporate uracil into DNA.  


Bone marrow cells from 15 patients with normal deoxyuridine (dU) suppression test results, 3 healthy subjects, and 11 patients with megaloblastic anemia caused by vitamin B12 or folate deficiency were examined for misincorporation of uracil into DNA. Cells were incubated with [5-3H] uridine for 2 hours and their DNA extracted. The DNA was hydrolyzed to deoxyribonucleosides with DNase 1, phosphodiesterase and alkaline phosphatase, and any dU present was separated from other deoxyribonucleosides by Aminex A6 chromatography. The quantity of dU/mg DNA and the radioactivity in the dU peak/mg DNA were then calculated. The results clearly showed that there was markedly increased uracil misincorporation into the DNA of vitamin B12- or folate-deficient marrow cells. Misincorporation of uracil into DNA may be an important biochemical lesion underlying both the megaloblastic change and the ineffectiveness of hematopoiesis in vitamin B12 and folate deficiency. PMID:8123857

Wickramasinghe, S N; Fida, S



Contribution of cobalamin analogues to plasma vitamin B12 concentrations in cattle.  


Plasma vitamin B12 concentrations in cattle were analysed by a radioisotope dilution assay using pig intrinsic factor and a microbiological assay using Euglena gracilis. Both assays provided similar results for samples of cattle plasma containing vitamin B12 concentrations ranging from 0.07 to 3.60 micrograms litre-1 (r = 0.95, P less than 0.001). The addition of excess cobinamide in the radioisotope dilution assay to block non-specific binding in the intrinsic factor preparation due to the presence of R-type binders, was used to determine the presence of cobalamin analogues. Cobalamin analogues accounted for up to 50 per cent of the total vitamin B12 concentration in samples of plasma from cows but were virtually undetectable in plasma from sheep. PMID:6438747

Halpin, C G; Harris, D J; Caple, I W; Petterson, D S



Distributions of dissolved vitamin B 12 and Co in coastal and open-ocean environments  

NASA Astrophysics Data System (ADS)

Distributions of dissolved vitamin B 12 and total dissolved Co were measured to gain an understanding of the cycling of these interdependent micronutrients in six marine settings including; an upwelling location, a semi-enclosed bay, two urban coastal systems, and two open ocean locations. Along the coast of Baja California, Mexico, concentrations of B 12 and dissolved Co varied from 0.2 to 11 pM and 180 to 990 pM, respectively. At a nearby upwelling station, vitamin B 12 and Co concentrations ranged from 0.3 to 7.0 pM and 22 to 145 pM, and concentrations did not correlate with upwelling intensity. Concentrations of B 12 were highest within Todos Santos Bay, a semi-enclosed bay off the coast of Baja California, Mexico, during a dinoflagellate bloom, ranging from 2 to 61 pM, while Co concentrations varied between 61 and 194 pM. In the anthropogenically impacted Long Island Sound, NY, U.S.A., B 12 levels were between 0.1 and 23 pM and Co concentrations varied from 60 to 1900 pM. However, anthropogenic inputs were not evident in B 12 levels in the San Pedro Basin, located outside Los Angeles, Ca, U.S.A., where concentrations of B 12 were 0.2-1.8 pM, approximating observed open ocean B 12 concentrations. In the Southern Ocean and North Atlantic Ocean, B 12 levels were 0.4-4 pM and 0.2-2 pM, respectively. Total Co concentrations in the Southern Ocean and North Atlantic tended to be low; measuring 26-59 pM and 15-80 pM, respectively. These low Co concentrations may limit B 12 synthesis and its availability to B 12-requiring phytoplankton because the total dissolved Co pool is not necessarily entirely bioavailable.

Panzeca, Caterina; Beck, Aaron J.; Tovar-Sanchez, Antonio; Segovia-Zavala, Jose; Taylor, Gordon T.; Gobler, Christopher J.; Sañudo-Wilhelmy, Sergio A.



Clinical and MRI manifestations of nitrous oxide induced vitamin B12 deficiency: A case report  

PubMed Central

A 50 year-old man was referred with history of acute ataxia and lower extremity paresthesia 10 days after general anesthesia with nitrous oxide. Cervical MRI showed long hypersignal lesion in posterior segment of the cord. Blood analysis revealed vitamin B12 deficiency. Nitrous oxide-induced myelopathy should be considered in patients who develop acute neurological manifestation after general anesthesia. It is recommended for physicians to think about symptoms and signs of B12 deficiency when evaluating patients in postoperative visits.

Safari, Anahid; Emadi, Farhad; Jamali, Elham



[A case of subacute combined degeneration with normal serum vitamin B12 level].  


A 40-year-old woman was admitted to our hospital because of pancytopenia with megaloblastic anemia. Two months later she complained of rapidly progressive gait disturbance and numbness in the distal part of limbs. She also told that her hair had turned totally gray in the third decade. Neurologically, mental state, cranial nerves and cerebellar functions were normal. Superficial sensations were impaired below the lower thoracic level and deep sensations were completely lost in the lower limbs. Moderate weakness was found in the lower limbs, symmetrically. Deep tendon reflexes were diminished in the upper limbs and absent in the lower limbs. Babinski's reflex was positive bilaterally. MR images of the spinal cord showed hyperintensity in the posterior column below the thoracic cord. Although the serum level of vitamin B12 was within normal range, serum homocysteine level was elevated markedly. Under the diagnosis of subacute combined degeneration (SCD) due to possible vitamin B12 deficiency, the treatment with intravenous injections of 500 micrograms/day of mecobalamin was undertaken. Muscle strength and sensory impairment improved progressively and she became able to walk with a cane. The coloration of her gray hair was also noted. After treatment, pancytopenia and megaloblastic anemia also markedly improved. Vitamin B12 became high in serum concentration and the serum level of homocysteine became normal. These clinical and laboratory findings support the diagnosis of SCD with normal serum level of vitamin B12 in our case, suggesting that the level of vitamin B12 in serum does not always correlate with that in tissue and, therefore, SCD should not be excluded just only by the reason of normal serum vitamin B12 level. PMID:14727562

Nagaishi, Akiko; Takashima, Hiroshi; Fukuda, Yasuo; Kuroda, Yasuo



Decreased vitamin B12 availability induces ER stress through impaired SIRT1-deacetylation of HSF1  

PubMed Central

Vitamin B12 (cobalamin) is a key determinant of S-adenosyl methionine (SAM)-dependent epigenomic cellular regulations related to methylation/acetylation and its deficiency produces neurodegenerative disorders by elusive mechanisms. Sirtuin 1 deacetylase (SIRT1) triggers cell response to nutritional stress through endoplasmic reticulum (ER) stress. Recently, we have established a N1E115 dopaminergic cell model by stable expression of a transcobalamin–oleosin chimera (TO), which impairs cellular availability of vitamin B12, decreases methionine synthase activity and SAM level, and reduces cell proliferation. In contrast, oleosin-transcobalamin chimera (OT) does not modify the phenotype of transfected cells. Presently, the impaired cellular availability of vitamin B12 in TO cells activated irreversible ER stress pathways, with increased P-eIF-2?, P-PERK, P-IRE1?, ATF6, ATF4, decreased chaperon proteins and increased pro-apoptotic markers, CHOP and cleaved caspase 3, through reduced SIRT1 expression and consequently greater acetylation of heat-shock factor protein 1 (HSF1). Adding either B12, SIRT1, or HSF1 activators as well as overexpressing SIRT1 or HSF1 dramatically reduced the activation of ER stress pathways in TO cells. Conversely, impairing SIRT1 and HSF1 by siRNA, expressing a dominant negative form of HSF1, or adding a SIRT1 inhibitor led to B12-dependent ER stress in OT cells. Addition of B12 abolished the activation of stress transducers and apoptosis, and increased the expression of protein chaperons in OT cells subjected to thapsigargin, a strong ER stress stimulator. AdoX, an inhibitor of methyltransferase activities, produced similar effects than decreased B12 availability on SIRT1 and ER stress by a mechanism related to increased expression of hypermethylated in cancer 1 (HIC1). Taken together, these data show that cellular vitamin B12 has a strong modulating influence on ER stress in N1E115 dopaminergic cells. The impaired cellular availability in vitamin B12 induces irreversible ER stress by greater acetylation of HSF1 through decreased SIRT1 expression, whereas adding vitamin B12 produces protective effects in cells subjected to ER stress stimulation.

Ghemrawi, R; Pooya, S; Lorentz, S; Gauchotte, G; Arnold, C; Gueant, J-L; Battaglia-Hsu, S-F



Potential cobalt limitation of vitamin B12 synthesis in the North Atlantic Ocean  

NASA Astrophysics Data System (ADS)

While recent studies have confirmed the ecological importance of vitamin B12, it is unclear whether the production of this vitamin could be limited by dissolved Co, a trace metal required for B12 biosynthesis, but found at only subnanomolar concentrations in the open ocean. Herein, we demonstrate that the spatial distribution of dissolved B12 (range: 0.13-5 pmol L-1) in the North Atlantic Ocean follows the abundance of total dissolved Co (range: 15-81 pmol L-1). Similar patterns were observed for bacterial productivity (range: 20-103 pmol 3H leucine L-1 hr-1) and algal biomass (range: 0.4-3.9 ?g L-1). In contrast, vitamin B1 concentrations (range: 0.7-30 pM) were decoupled from both Co and B12 concentrations. Cobalt amendment experiments carried out in low-dissolved Co waters (˜20 pmol L-1) enhanced B12 production two-fold over unamended controls. This study provides evidence that B12 synthesis could be limited by the availability of Co in some regions of the world ocean.

Panzeca, C.; Beck, A. J.; Leblanc, K.; Taylor, G. T.; Hutchins, D. A.; SañUdo-Wilhelmy, S. A.



Serial nerve conduction studies in vitamin B 12 deficiency-associated polyneuropathy  

Microsoft Academic Search

This report is on a 22-year-old male vegetarian with acute polyneuropathy secondary to vitamin B12 deficiency. He presented with weakness and numbness of the distal limbs and absent deep tendon reflex in all four extremities.\\u000a Nerve conduction study (NCS) showed an axonal type sensori-motor polyneuropathy. Serum biochemical studies revealed vitamin\\u000a B12 level of 119 pg\\/mL (reference range 185–710 pg\\/mL), with elevated creatine

Chi-Ren Huang; Wen-Neng Chang; Nai-Wen Tsai; Cheng-Hsien Lu



Studies on the spin Hamiltonian parameters of vitamin B 12r  

NASA Astrophysics Data System (ADS)

The spin Hamiltonian parameters g factors gi ( i = x, y, z) and the hyperfine structure constants Ai of vitamin B 12r have been theoretically studied from the perturbation formulas of these parameters for a Co 2+(3d 7) ion with low spin ( S = 1/2) in rhombically distorted octahedra. The related crystal-field parameters are determined from the point-charge-dipole model and the local structure around Co 2+ in vitamin B 12r. The theoretical spin Hamiltonian parameters are in good agreement with the experimental data.

Wu, Shao-Yi; Wei, Li-Hua; Zhang, Zhi-Hong; Wang, Xue-Feng



Notes from the field: update: vitamin B12 deficiency among bhutanese refugees resettling in the United States, 2012.  


In 2008, clinicians performing routine medical examinations in the United States reported high rates of hematologic and neurologic disorders caused by vitamin B12 deficiency in resettled Bhutanese refugees. To confirm this finding, CDC screened Bhutanese refugees' serum samples for vitamin B12 levels and found vitamin B12 deficiency in 64% (n = 99) of samples obtained before departure and 27% (n = 64) of samples obtained after arrival in the United States. In response, CDC recommended that arriving Bhutanese refugees receive oral vitamin B12 supplements and nutrition advice. In 2012, based on anecdotal reports of decreasing rates of vitamin B12 deficiency in this population, CDC worked with select domestic refugee health programs to determine if the recommendations had reduced the vitamin B12 deficiency rate among Bhutanese refugees. PMID:25029113

Cuffe, Kendra; Stauffer, William; Painter, John; Shetty, Sharmila; Montour, Jessica; Zhou, Weigong



Beyond catalysis: vitamin B12 as a cofactor in gene regulation.  


Vitamin B12 is well known as an enzyme cofactor in the catalysis of many important biological reactions, and the role of B12 in regulation of bacterial gene expression as a ligand of riboswitches is well established. Only recently evidence has emerged that B12 can also affect bacterial gene expression by acting as a cofactor of regulatory proteins. In 2011 a role of B12 as a cofactor of the transcriptional repressor of carotenogenesis, CarH, in Myxococcus xanthus was reported. B12 is required for light-dependent DNA binding by CarH, which can therefore be considered to be a new type of photoreceptor. Cheng et al. (2014) report the identification of B12 as a cofactor of the AerR protein in Rhodobacter capsulatus. AerR acts as an antirepressor of the CrtJ protein, which represses photosynthesis genes when binding to its target promoters. As in Myxococcus B12 may have the role of a chromophore in photoreception, but it is suggested that a main function of AerR is the sensing of B12. The co-regulation of the pathways is beneficial because the syntheses of B12 , haem and bacteriochlorophylls share common precursors and the accumulation of the free molecules is toxic. PMID:24330414

Klug, Gabriele



Folic acid and vitamin B12 levels in pregnancy and their relation to megaloblastic anaemia  

PubMed Central

There is a significant fall in the serum folic acid level during pregnancy, reaching its lowest level at term. This is most pronounced in twin pregnancies. A similar but less spectacular fall occurs in the vitamin B12 concentration. In megaloblastic anaemia both folic acid and vitamin B12 levels are lower than in other pregnant women. The degree of megaloblastic change in the bone marrow, as measured by the type and number of megaloblasts, is reflected in the vitamin levels, cases with florid megaloblastosis showing the most marked depression of vitamin B12 and folic acid activity. Although there is a significant difference in the mean folic acid levels between megaloblastic and normoblastic pregnant women, a considerable overlap exists between individual values in the two groups. When the labile folic-acid factor is determined separately the test becomes much more specific. In the present series, all cases of megaloblastic anaemia yielded labile-factor levels below 1·0 m?g. per ml., while a similar value was encountered in only one of 35 normal pregnancies. In five women with megaloblastic anaemia the vitamin B12 concentration was less than 100 ??g. per ml. but rose to normal levels on folic acid therapy alone. Images

Ball, E. W.; Giles, C.



Cloning and expression of the gene for the vitamin B12 receptor protein in the outer membrane of Escherichia coli.  

PubMed Central

The transport of cyanocobalamin (vitamin B12) in cells of Escherichia coli is dependent on a receptor protein (BtuB protein) located in the outer membrane. A 9.1-kilobase pair BamHI fragment carrying the btuB gene was cloned from a specialized transducing phage into multicopy plasmids. Insertions of transposon Tn1000 which prevented production of the receptor localized btuB to a 2-kilobase pair region. Further subcloning allowed isolation of this region as a 2.3-kilobase pair Sau3A fragment. The BtuB+ plasmids were shown by maxicell analysis to encode a polypeptide with a molecular weight of 66,000 in the outer membrane. This polypeptide was missing in cells with Tn1000 insertions in btuB and was reduced in amount upon growth of plasmid-bearing cells in repressing concentrations of vitamin B12. Several Tn1000 insertions outside the 5' end of the coding region exhibited reduced production of receptor. A deletion at the 3' end of btuB resulted in formation of an altered receptor. Amplified production of this polypeptide was associated with increased levels of binding of the receptor's ligands (vitamin B12 and phage BF23), increased rates of vitamin B12 uptake, and altered susceptibility to the group E colicins. Deficiency in various major outer membrane proteins did not affect production of the btuB product, and the amplified levels of this protein partially reversed the tolerance to E colicins seen in these mutants. Images

Heller, K; Mann, B J; Kadner, R J



Low Vitamin B12 Levels among Newly-Arrived Refugees from Bhutan, Iran and Afghanistan: A Multicentre Australian Study  

PubMed Central

Background Vitamin B12 deficiency is prevalent in many countries of origin of refugees. Using a threshold of 5% above which a prevalence of low Vitamin B12 is indicative of a population health problem, we hypothesised that Vitamin B12 deficiency exceeds this threshold among newly-arrived refugees resettling in Australia, and is higher among women due to their increased risk of food insecurity. This paper reports Vitamin B12 levels in a large cohort of newly arrived refugees in five Australian states and territories. Methods In a cross-sectional descriptive study, we collected Vitamin B12, folate and haematological indices on all refugees (n?=?916; response rate 94% of eligible population) who had been in Australia for less than one year, and attended one of the collaborating health services between July 2010 and July 2011. Results 16.5% of participants had Vitamin B12 deficiency (<150 pmol/L). One-third of participants from Iran and Bhutan, and one-quarter of participants from Afghanistan had Vitamin B12 deficiency. Contrary to our hypothesis, low Vitamin B12 levels were more prevalent in males than females. A higher prevalence of low Vitamin B12 was also reported in older age groups in some countries. The sensitivity of macrocytosis in detecting Vitamin B12 deficiency was only 4.6%. Conclusion Vitamin B12 deficiency is an important population health issue in newly-arrived refugees from many countries. All newly-arrived refugees should be tested for Vitamin B12 deficiency. Ongoing research should investigate causes, treatment, and ways to mitigate food insecurity, and the contribution of such measures to enhancing the health of the refugee communities.

Benson, Jill; Phillips, Christine; Kay, Margaret; Webber, Murray T.; Ratcliff, Alison J.; Correa-Velez, Ignacio; Lorimer, Michelle F.



Do high blood folate concentrations exacerbate metabolic abnormalities in people with low vitamin B-12 status?123  

PubMed Central

Background: In elderly individuals with low serum vitamin B-12, those who have high serum folate have been reported to have greater abnormalities in the following biomarkers for vitamin B-12 deficiency: low hemoglobin and elevated total homocysteine (tHcy) and methylmalonic acid (MMA). This suggests that folate exacerbates vitamin B-12–related metabolic abnormalities. Objective: We determined whether high serum folate in individuals with low serum vitamin B-12 increases the deleterious effects of low vitamin B-12 on biomarkers of vitamin B-12 cellular function. Design: In this cross-sectional study, 2507 university students provided data on medical history and exposure to folic acid and vitamin B-12 supplements. Blood was collected to measure serum and red blood cell folate (RCF), hemoglobin, plasma tHcy, and MMA, holotranscobalamin, and ferritin in serum. Results: In subjects with low vitamin B-12 concentrations (<148 pmol/L), those who had high folate concentrations (>30 nmol/L; group 1) did not show greater abnormalities in vitamin B-12 cellular function in any area than did those with lower folate concentrations (?30 nmol/L; group 2). Group 1 had significantly higher holotranscobalamin and RCF, significantly lower tHcy, and nonsignificantly lower (P = 0.057) MMA concentrations than did group 2. The groups did not differ significantly in hemoglobin or ferritin. Compared with group 2, group 1 had significantly higher mean intakes of folic acid and vitamin B-12 from supplements and fortified food. Conclusions: In this young adult population, high folate concentrations did not exacerbate the biochemical abnormalities related to vitamin B-12 deficiency. These results provide reassurance that folic acid in fortified foods and supplements does not interfere with vitamin B-12 metabolism at the cellular level in a healthy population.

Mills, James L; Carter, Tonia C; Scott, John M; Troendle, James F; Gibney, Eileen R; Shane, Barry; Kirke, Peadar N; Ueland, Per M; Brody, Lawrence C; Molloy, Anne M



Effect of Combined Folic Acid, Vitamin B6, and Vitamin B12 on Cancer Risk: Results from a Randomized Trial  

PubMed Central

Context Folate, vitamin B6, and vitamin B12 are thought to play an important role in cancer prevention. Objective To evaluate the effect of combined folic acid, vitamin B6, and vitamin B12 treatment on cancer risk in women at high risk for cardiovascular disease. Design, Setting, and Participants In the Women’s Antioxidant and Folic Acid Cardiovascular Study, 5442 US female health professionals aged 42 years or older with preexisting cardiovascular disease or 3 or more coronary risk factors were randomly assigned to receive either a daily combination of folic acid, vitamin B6, and vitamin B12 or placebo in April 1998, and treated through July 31, 2005 for 7.3 years. Intervention Daily supplementation of a combination of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 (n=2721) or placebo (n=2721). Main Outcome Measures Confirmed newly diagnosed total invasive cancer. Results A total of 379 women developed invasive cancer (187 in the active group and 192 in the placebo group). Compared with placebo, women receiving combined folic acid, vitamin B6, and vitamin B12 had similar risk of developing total invasive cancer (101.1/10000 person-years vs 104.3/10000 person-years for the active vs placebo group; hazard ratio, 0.97; 95% confidence interval, 0.79–1.18; P=.75), breast cancer (37.8/10000 person-years vs 45.6/10000 person-years; hazard ratio, 0.83; 95% confidence interval, 0.60–1.14; P=.24), and any cancer death (24.6/10000 person-years vs 30.1/10000 person-years; hazard ratio, 0.82; 95% confidence interval, 0.56–1.21; P=.32). Conclusions Combined folic acid, vitamin B6, and vitamin B12 treatment had no significant effect on overall risk of total invasive cancer or breast cancer among women during folic acid fortification era. Trial Registration Identifier: NCT00000541

Zhang, Shumin M.; Cook, Nancy R.; Albert, Christine M.; Gaziano, J. Michael; Buring, Julie E.; Manson, JoAnn E.



[Neural tube defects and vitamin B12: a report of three cases].  


Periconceptional folic acid supplementation reduces the frequency of embryological neural tube defects (NTD). This fact led the USA to fortify grain products with folic acid (140 microg/100 g) starting in January 1998, with a resultant decrease in the incidence of NTD. Folate deficiency is thus confirmed to be a risk factor for NTD. However, in a prospective study, we investigated three women who conceived a fetus with NTD; no folate deficiency was found in these women but all three had decreased vitamin B12 levels (cobalamin), which can be an other risk factor. Samples were obtained from two women in Algeria, 2 days after interruption of pregnancy, and from a vegetarian woman, in France, one month after interruption of pregnancy. Red cell folate and plasma folate, vitamin B12, B6 and homocysteine were assayed and the mutations C677T (in metylenetetrahydrofolate reductase gene), A2756G (in methionine synthase gene) and A66G (in methionine synthase reductase gene) were sought. Elevated plasma folate levels were found in both Algerian women. Vitamin B 12 levels in all three women were decreased or in the lowest quartile of normal values. One woman presented simultaneously a vitamin B 12 deficiency, and heterozygous mutations in the three genes. The second woman presented a A66G homozygous mutation and the third heterozygous C677T and A66G mutations. Acquired and inborn factors are intricated in some cases of pregnancies with NTD and B 12 deficiency can be responsible for intracellular folate cycle failure. It would therefore be advisable to consider fortifying grain products with both folic acid and vitamin B12. PMID:15047478

Candito, M; Houcher, B; Boisson, C; Abellard, J; Demarcq, M-J; Guéant, J-L; Benhacine, K; Gérard, P; Van Obberghen, E



[A simple health control for the elderly. Screening for vitamin B12 deficiency and thyroid disease].  


Screening for vitamin B12 deficiency and thyroid disease is cheap and enables early diagnosis to be made and treatment to be started while it is still simple and can prevent the development of such serious conditions as dementia, depression, or irreversible tissue damage. In 1995-6, 83% (126/151) of all 75-year-olds in Härryda, a district (population 28,500) to the east of Gothenburg, agreed to undergo a health control designed to detect hypo- or hyper-thyroidism or vitamin B12 deficiency among elderly residents without symptoms (or with atypical symptoms not easily recognised). Of the 126 participants, four (3%) had low plasma cobalamin (vitamin B12) levels (a figure similar to or lower than those reported by others), and were treated with vitamin B12 after further examination; eight (6%) had serum thyroid stimulating hormone (TSH) levels below the lower normal limit, though further examination showed all eight to be euthyroid; and two (1.6%) were diagnosed as being hypothyroid (a lower prevalence than figures reported elsewhere), and were treated with laevothyroxine. The findings suggest that such screening might be useful in primary care. However, the clinical diagnosis of vitamin B12 deficiency, and of hypo- or hyperthyroidism, is often difficult, especially in the elderly; and although a low serum TSH level is also considered to be a reliable marker of hyperthyroidism, like others this study showed that it may occur even in the absence of disease. Thus, serum TSH and plasma B12 levels are useful screening variables, but need to be complemented by other tests before diagnosis is set. PMID:9424529

Bondeson, E; Meisel, T; Eggertsen, R



Reduced dietary intake of vitamin B12 and folate in patients with recurrent aphthous stomatitis  

PubMed Central

BACKGROUND Recurrent aphthous stomatitis (RAS), commonly referred to as canker sores, is a very common and painful oral mucosal disease. Although the etiology of RAS is not well understood, a number of factors may play a role, including nutritional deficiencies. The objective of this study was to compare dietary vitamin intake in RAS patients to that of a control group. METHODS One hundred subjects, who had suffered at least three episodes of minor RAS in the previous 12 months, completed a detailed Diet History Questionnaire designed and validated by the US National Institutes of Health. DietCalc software was used to calculate daily dietary intakes of nine different vitamins in the study subjects. Daily intakes were energy-adjusted and compared to age- and gender-matched nutrient intake data on 9033 subjects from the US National Health and Nutrition Examination Survey. RESULTS The study subjects had significantly lower daily intake of vitamin B12 (P < 0.0002) and folate (P < 0.0001) as compared to the controls. CONCLUSIONS Our results demonstrate that patients with recurrent aphthous stomatitis are more likely to have lower dietary intakes of vitamin B12 and folate than a control group. These results support and extend previous studies indicating a link between the etiology of RAS and hematological deficiencies of vitamin B12 and folate. These findings suggest that consuming sufficient amounts of these vitamins may be a useful strategy to reduce the number and/or duration of RAS episodes.

Kozlak, Scott T.; Walsh, Stephen J.; Lalla, Rajesh V.



Systemic and local peripheral injections of vitamin B12 suppressed orofacial nociception induced by formalin in rats.  


Vitamin B12 has many biological functions including antinociceptive property. This study was designed to investigate the effects of local peripheral (into upper lip) and systemic injection of vitamin B12 and diclofenac on the orofacial pain. Orofacial pain was induced by subcutaneous injection 50?µL of a diluted formalin solution (1.5%) in the right upper lip. The time spent face rubbing performed with ipsilateral forepaw was measured in 3?min blocks for a period of 45?min. Formalin produced a biphasic pattern (early phase: 0-3?min and second phase: 15-33?min) of pain response. Systemic (1, 2 and 4?mg/kg) and local peripheral (2.5, 5 and 10?µg/rat) injections of vitamin B12 significantly attenuated the second phase of formalin-induced pain. The same results were obtained from systemic (2 and 4?mg/kg) and local peripheral (100 and 200?µg/rat) injections of diclofenac. Systemic co-administrations of vitamin B12 and diclofenac increased vitamin B12-induced antinociception. Local co-administrations of vitamin B12 and diclofenac enhanced antinociception induced by diclofenac. The obtained results indicated that vitamin B12 and diclofenac produced powerful suppressing effects on orofacial inflammatory pain. Co-treatments with vitamin B12 and diclofenac produced more antinociceptive effects. Inhibition of cyclooxygenase (COX) pathway may be involved in antinociception induced by vitamin B12. PMID:23986308

Erfanparast, A; Escort, M; Tamaddonfard, E; Maroufi, S; Kazemi-Shojaei, S; Dabbaghi, M; Taati, M



Copper control of bacterial nitrous oxide emission and its impact on vitamin B12-dependent metabolism  

PubMed Central

Global agricultural emissions of the greenhouse gas nitrous oxide (N2O) have increased by around 20% over the last 100 y, but regulation of these emissions and their impact on bacterial cellular metabolism are poorly understood. Denitrifying bacteria convert nitrate in soils to inert di-nitrogen gas (N2) via N2O and the biochemistry of this process has been studied extensively in Paracoccus denitrificans. Here we demonstrate that expression of the gene encoding the nitrous oxide reductase (NosZ), which converts N2O to N2, is regulated in response to the extracellular copper concentration. We show that elevated levels of N2O released as a consequence of decreased cellular NosZ activity lead to the bacterium switching from vitamin B12-dependent to vitamin B12-independent biosynthetic pathways, through the transcriptional modulation of genes controlled by vitamin B12 riboswitches. This inhibitory effect of N2O can be rescued by addition of exogenous vitamin B12.

Sullivan, Matthew J.; Gates, Andrew J.; Appia-Ayme, Corinne; Rowley, Gary; Richardson, David J.



Improved vitamin B12 fermentation process by adding rotenone to regulate the metabolism of Pseudomonas denitrificans.  


Our previous research had revealed that the dissolved oxygen limitation was more favorable for vitamin B12 fermentation, due to its inducement to the increased glycolytic flux in Pseudomonas denitrificans. In this paper, a novel strategy was implemented to further investigate the metabolic characteristics of P. denitrificans under different oxygen supply levels, by exogenously adding rotenone (a respiratory chain inhibitor interfering with the oxygen consumption) to the fermentation broths. Compared to the fermentation process without rotenone treatment, it was observed that 5 mg/L rotenone treatment could significantly strengthen the glycolytic flux of P. denitrificans via activating the key glycolytic enzymes (phosphofructokinase and pyruvate kinase), resulting in the accelerated generations of anterior precursors (glutamate and 5-aminolevulinic acid) for vitamin B12 biosynthesis. Although 5 mg/L rotenone treatment had a negative effect on cell growth of P. denitrificans, the vitamin B12 yield was increased from 48.28?±?0.62 mg/L to 54.70?±?0.45 mg/L, which further proved that an increased glycolytic flux in P. denitrificans was a consequence of higher vitamin B12 production. PMID:24687557

Cheng, Xin; Chen, Wei; Peng, Wei-Fu; Li, Kun-Tai



Synthesis of Methyl Groups catalysed by Vitamin B12r in vitro  

Microsoft Academic Search

THE use of Raney metal catalysts for the reductive methylation of amines with formaldehyde and hydrogen is well known1. We wish to report that this reaction is also catalysed by vitamin B12r in vitro, and thus is potentially of biochemical importance. For example, a 1 : 1 mixture of aniline and formaldehyde in methanol and water absorbs hydrogen at room

G. N. Schrauzer; R. J. Windgassen



Homocysteine, vitamin B12 and folate levels in premature coronary artery disease  

Microsoft Academic Search

BACKGROUND: Hyperhomocysteinemia is known as an independent risk factor of atherosclerosis, but the probable role of hyperhomocysteinemia in premature Coronary Artery Disease (CAD) is not well studied. The aim of this study was to assess the role of hyperhomocysteinemia, folate and Vitamin B12 deficiency in the development of premature CAD. METHODS: We performed an analytical case-control study on 294 individuals

Saeed Sadeghian; Faramarz Fallahi; Mojtaba Salarifar; Gholamreza Davoodi; Mehran Mahmoodian; Nader Fallah; Soodabeh Darvish; Abbasali Karimi



The structural basis for molecular recognition by the vitamin B 12 RNA aptamer  

Microsoft Academic Search

Previous solution structures of ligand-binding RNA aptamers have shown that molecular recognition is achieved by the folding of an initially unstructured RNA around its cognate ligand, coupling the processes of RNA folding and binding. The 3 Å crystal structure of the cyanocobalamin (vitamin B12) aptamer reported here suggests a different approach to molecular recognition in which elements of RNA secondary

Jay C. Nix; Django Sussman; Charles Wilson



Biosynthesis of vitamin B 12: the multi-enzyme synthesis of precorrin-4 and factor IV  

Microsoft Academic Search

Background: In order to study the biosynthesis of vitamin B12, it is necessary to produce various intermediates along the biosynthetic pathway by enzymic methods. Recently, information on the organisation of the biosynthetic pathway has permitted the selection of the set of enzymes needed to biosynthesise any specific identified intermediate. The aim of the present work was to use recombinant enzymes

N. Patrick J. Stamford; Sandhya Duggan; Yongfu Li; Alex I. D. Alanine; Joël Crouzet; Alan R. Battersby



Nutritional modulation of gene expression and homocysteine utilization by vitamin B12.  


Vitamins B12, B6, and folic acid converge at the homocysteine metabolic junction where they support the activities of two key enzymes involved in intracellular homocysteine management, methionine synthase (MS) and cystathionine beta-synthase. The molecular mechanism for the regulation of homocysteine metabolism by B12 supplementation has been investigated in this study. B12 supplementation does not alter mRNA or protein turnover rates but induces translational up-regulation of MS by shifting the mRNA from the ribonucleoprotein to the polysome pool. The B12-responsive element has been localized by deletion analysis using a reporter gene assay to a 70-bp region located at the 3' end of the 5'-untranslated region of the MS mRNA. The cellular consequence of the B12 response is a 2- and 3.5-fold increase in the flux of homocysteine through the MS-dependent transmethylation pathway in HepG2 and 293 cells, respectively. It is speculated that B12-induced up-regulation of MS may have evolved as an adaptive strategy for rapidly sequestering an essential and rare nutrient whose availability may have been limited in the evolutionary history of mammals, a problem that is exacerbated by the absence of this vitamin from the plant kingdom. PMID:12670934

Oltean, Sebastian; Banerjee, Ruma



Relations of vitamin B12, vitamin B6, folate, and homocysteine to cognitive performance in the Normative Aging Study1  

Microsoft Academic Search

We investigated the relations between plasma concentrations of homocysteine and vitamins B- 12 and B-6 and folate, and scores from a battery of cognitive tests for 70 male subjects, aged 54-81 y, in the Normative Aging Study. Lower concentrations of vitamin B-l2 (P = 0.04) and folate (P = 0.003) and higher concentrations of homocysteine (P = 0.0009) were associated

Karen M Riggs; Avron Spiro Ill; Katherine Tucker; David Rush


DNA methylation and subclinical vitamin deficiency of folate, pyridoxal-phosphate and vitamin B12 in chronic alcoholics  

Microsoft Academic Search

Alcohol abuse is known to adversely affect folate, vitamin B12 and pyridoxal-phosphate metabolism, which are required for de novo synthesis of methionine. Methionine is the precursor of S-adenosylmethionine, the principal methylating agent in the organism, including DNA. The objective of this study was to measure DNA methylation in peripheral lymphocytes and the circulating concentrations of these three vitamins in chronic

M. Cravo; L. Glória; M. E. Camilo; M. Resende; J. Neves Cardoso; C. Nobre Leitão; F. Costa Mira



Vitamin B12 levels are not affected by radioiodine ablation of the thyroid.  


Objective. Radioiodine administered for the treatment of hyperthyroidism and thyroid cancer can be taken up by many non-thyroid tissues which express sodium iodide symporter. Though gastric mucosa takes up radioiodine, its impact on parietal cell has not been evaluated. The aim of the present study was to compare vitamin B12 and homocysteine concentrations in patients with thyroid disorders treated by radioiodine ablation with those in control population without radioiodine exposure.Methods. Patients with Graves' disease, toxic multinodular goiter (TMNG), toxic adenoma (TA) or differentiated thyroid cancer (DTC) who had received 131I were included as "patients". Healthy persons and patients having Graves' disease but without exposure to radioiodine were recruited as "controls". A total of 35 patients and 35 controls were included. Patients were divided into Graves' disease and non-Graves' disease (TMNG, TA, DTC) groups. Graves' disease patients were compared with Graves' disease controls while non-Graves' disease patients were compared with healthy controls.Results. In the Graves' disease group, median vitamin B12 concentration was 240 pg/ml (IQR: 148 - 371) in patients (n=23) and 195 pg/ml (IQR: 140 - 291 pg/ml) (p=0.13, ns) in controls (n=24). In the non-Graves' disease group, median serum vitamin B12 concentration was 147 pg/ml (IQR: 124 - 325pg/ml) in patients (n=12) and 190 pg/ml (IQR: 157 - 373 pg/ml) (p=0.34, ns) in healthy controls (n=11). Homocysteine concentrations were also similar in compared groups of patients and controls.Conclusions. Radioiodine ablation does not cause vitamin B12 deficiency. However, a prospective study with a larger number of patients is required to confirm this finding. Keywords: radioiodine ablation, vitamin B12, gastric mucosa, parietal cells. PMID:24824803

Potham, S K; Vaikkakara, S; Sachan, A; V, S P; Kalawat, T C; Ravi, P; Sunil, E; Rajitha, D; Arun, M; Sailaja, A



Serum vitamin B12 and folate concentrations and the effect of the Mediterranean diet on vulnerable populations.  


Low vitamin B12 and folate levels in expectant mothers may lead to low stores in babies. The aim of this study was to determine the frequencies of vitamin B12 and folate deficiencies in pregnant women and neonates, and to assess the effect of maternal vitamin status on babies' vitamin levels in the Aegean region of Turkey, where the Mediterranean diet (mainly fresh fruits and vegetables) is adopted. We studied 72 pregnant women and their singleton-term babies. Venous blood samples of expectant mothers were collected 1 h before delivery and cord blood of babies were obtained at birth. The mean vitamin B12 in maternal and cord blood serum was 163.1 ± 72.0 pg/mL and 146.2 ± 102.5 pg/mL, and the mean folate, 9.8 ± 4.8 ng/mL and 15.8 ± 3.8 ng/mL, respectively. There were statistically significant correlation between maternal and cord blood serum vitamin B12 (r = 0.61, P = .04) and folate levels (r = 0.65, P < .001). 70.8% of the mothers and 83.9% of the babies were vitamin B12 deficient (<200 pg/mL). Neither group showed folate deficiency. The mean level of vitamin B12 in mothers significantly varied by the type of diet (241.6 (72.1) pg/mL versus 155.9 (68.2) pg/mL; P = .012). Vitamin B12 deficiency in pregnant women and neonates may be a public health problem in our community. The Mediterranean diet in these vulnerable groups may be an aggravating factor for vitamin B12 deficiency. Prenatal screening of all expectant mothers, prenatal supplementation of vitamin B12, and an increase in animal-source food intake may improve expectant mother's vitamin B12 level. PMID:24088029

Balc?, Yasemin I??k; Ergin, Ahmet; Karabulut, Aysun; Polat, Aziz; Do?an, Mustafa; Küçükta?c?, Kaz?m



Influence of Meal on Plasma Folate and Vitamin B12, by Three Methods - and on Vitamin B6, Homocysteine and Red Blood Cell Folate  

Microsoft Academic Search

Vitamins are brought by meals. Some of them are cofactors in homocysteine metabolism, and, if plasma homo- cysteine values are not known to have a circadian rhythm, little is known about meal influence on blood folate, and vitamins B12 and B6. The aim of this study is to analyze the effect of breakfast and lunch on plasma folate, vitamins B12

Mirande Candito; Bakhouche Houcher; François Roux; Genevieve Potier de Courcy; Anne Caramella; Frederick Berthier; Abdelhamid Aberkane



Enhanced therapeutic effect of methotrexate in experimental rat leukemia after inactivation of cobalamin (vitamin B12) by nitrous oxide  

Microsoft Academic Search

Exposure to nitrous oxide interferes selectively with the coenzyme function of vitamin B12 and causes inactivation of methionine synthetase, with subsequent impairment of folate metabolism and reduction of cellular proliferation. In a rat leukemia model (BNML) we investigated the combined administration of nitrous oxide, inactivating vitamin B12, and methotrexate (MTX), a folate antagonist inhibiting the enzyme dihydrofolate reductase. Through different

A. C. M. Kroes; J. Lindemans; M. Schoester; J. Abels



Vitamin B12-dependent taurine synthesis regulates growth and bone mass  

PubMed Central

Both maternal and offspring-derived factors contribute to lifelong growth and bone mass accrual, although the specific role of maternal deficiencies in the growth and bone mass of offspring is poorly understood. In the present study, we have shown that vitamin B12 (B12) deficiency in a murine genetic model results in severe postweaning growth retardation and osteoporosis, and the severity and time of onset of this phenotype in the offspring depends on the maternal genotype. Using integrated physiological and metabolomic analysis, we determined that B12 deficiency in the offspring decreases liver taurine production and associates with abrogation of a growth hormone/insulin-like growth factor 1 (GH/IGF1) axis. Taurine increased GH-dependent IGF1 synthesis in the liver, which subsequently enhanced osteoblast function, and in B12-deficient offspring, oral administration of taurine rescued their growth retardation and osteoporosis phenotypes. These results identify B12 as an essential vitamin that positively regulates postweaning growth and bone formation through taurine synthesis and suggests potential therapies to increase bone mass.

Roman-Garcia, Pablo; Quiros-Gonzalez, Isabel; Mottram, Lynda; Lieben, Liesbet; Sharan, Kunal; Wangwiwatsin, Arporn; Tubio, Jose; Lewis, Kirsty; Wilkinson, Debbie; Santhanam, Balaji; Sarper, Nazan; Clare, Simon; Vassiliou, George S.; Velagapudi, Vidya R.; Dougan, Gordon; Yadav, Vijay K.



Vitamin B12-dependent taurine synthesis regulates growth and bone mass.  


Both maternal and offspring-derived factors contribute to lifelong growth and bone mass accrual, although the specific role of maternal deficiencies in the growth and bone mass of offspring is poorly understood. In the present study, we have shown that vitamin B12 (B12) deficiency in a murine genetic model results in severe postweaning growth retardation and osteoporosis, and the severity and time of onset of this phenotype in the offspring depends on the maternal genotype. Using integrated physiological and metabolomic analysis, we determined that B12 deficiency in the offspring decreases liver taurine production and associates with abrogation of a growth hormone/insulin-like growth factor 1 (GH/IGF1) axis. Taurine increased GH-dependent IGF1 synthesis in the liver, which subsequently enhanced osteoblast function, and in B12-deficient offspring, oral administration of taurine rescued their growth retardation and osteoporosis phenotypes. These results identify B12 as an essential vitamin that positively regulates postweaning growth and bone formation through taurine synthesis and suggests potential therapies to increase bone mass. PMID:24911144

Roman-Garcia, Pablo; Quiros-Gonzalez, Isabel; Mottram, Lynda; Lieben, Liesbet; Sharan, Kunal; Wangwiwatsin, Arporn; Tubio, Jose; Lewis, Kirsty; Wilkinson, Debbie; Santhanam, Balaji; Sarper, Nazan; Clare, Simon; Vassiliou, George S; Velagapudi, Vidya R; Dougan, Gordon; Yadav, Vijay K



Geographical gradients of dissolved Vitamin B12 in the Mediterranean Sea  

PubMed Central

Most eukaryotic phytoplankton require vitamin B12 to grow. However, the cycling of this organic growth factor has received substantially less attention than other bioactive substances such as trace metals in the marine environment. This is especially true in the Mediterranean Sea, where direct measurements of dissolved vitamins have never been reported. We report here the first direct measurements of dissolved vitamin B12 across longitudinal gradients in Mediterranean waters. The range of vitamin B12 concentrations measured over the whole transect was 0.5–6.2 pM, which is slightly higher than the range (undetectable—4 pM) of ambient concentrations measured in other open ocean basins in the Pacific and Atlantic oceans. The concentrations measured in the western basin were significantly higher (p < 0.05) than those of the eastern basin. They were positively correlated with chlorophyll concentrations in the most western part of the basin, and did not show any significant correlation with any other biological variables in other regions of the sampling transect.

Bonnet, S.; Tovar-Sanchez, A.; Panzeca, C.; Duarte, C. M.; Ortega-Retuerta, E.; Sanudo-Wilhelmy, S. A.



Vitamin B12 deficiency in Caenorhabditis elegans results in loss of fertility, extended life cycle, and reduced lifespan?  

PubMed Central

Vitamin B12 (B12) deficiency has been linked to developmental disorders, metabolic abnormalities, and neuropathy; however, the mechanisms involved remain poorly understood. Caenorhabditis elegans grown under B12-deficient conditions for five generations develop severe B12 deficiency associated with various phenotypes that include decreased egg-laying capacity (infertility), prolonged life cycle (growth retardation), and reduced lifespan. These phenotypes resemble the consequences of B12 deficiency in mammals, and can be induced in C. elegans in only 15 days. Thus, C. elegans is a suitable animal model for studying the biological processes induced by vitamin deficiency.

Bito, Tomohiro; Matsunaga, Yohei; Yabuta, Yukinori; Kawano, Tsuyoshi; Watanabe, Fumio



The prevalence of cobalamin deficiency among vegetarians assessed by serum vitamin B12: a review of literature.  


Individuals following vegetarian diets are at risk for developing vitamin B12 deficiency owing to suboptimal intake. As vitamin B12 is essential for the synthesis of nucleic acids, erythrocytes and in the maintenance of myelin, deficiency may result in a variety of symptoms. Some of these symptoms may be severe while others may be irreversible. The objective of this review was to assess vitamin B12 deficiency, based on reported serum vitamin B12, among individuals adhering to different types of vegetarian diets. A systematic literature search was carried out using multiple search engines including PubMed, Medline, CINAHL plus, ERIC, Nursing and Allied Health Collection and Nursing/Academic Edition. The inclusion criteria consisted of original studies that assessed serum vitamin B12, studies written in English, non-case studies and studies that reported actual percentages of vitamin B12 deficiency. Forty research studies were included. The deficiency prevalence among infants reached 45%. The deficiency among the children and adolescents ranged from 0 to 33.3%. Deficiency among pregnant women ranged from 17 to 39%, dependent on the trimester. Adults and elderly individuals had a deficiency range of 0-86.5%. Higher deficiency prevalence was reported in vegans than in other vegetarians. Thus, with few exceptions, the reviewed studies documented relatively high deficiency prevalence among vegetarians. Vegans who do not ingest vitamin B12 supplements were found to be at especially high risk. Vegetarians, especially vegans, should give strong consideration to the use of vitamin B12 supplements to ensure adequate vitamin B12 intake. Vegetarians, regardless of the type of vegetarian diet they adhere to, should be screened for vitamin B12 deficiency. PMID:24667752

Pawlak, R; Lester, S E; Babatunde, T



Characterisation of vitamin B12 immunoaffinity columns and method development for determination of vitamin B12 in a range of foods, juices and pharmaceutical products using immunoaffinity clean-up and high performance liquid chromatography with UV detection.  


New rapid and simpler procedures, using immunoaffinity columns, have been developed for the determination of vitamin B12 in a range of samples including three different US National Institute of Standard and Technology (NIST) Reference Materials, infant formula, powdered energy drinks and bars, wheat breakfast cereal, carbonated soft drinks, fruit juices and vitamin B12 tablets. The procedures involved extraction of vitamin B12 using water or sodium acetate buffer and enzyme digestion (using pepsin or alpha-amylase, or both) if necessary. The extract was clarified and passed through "EASI-EXTRACT Vitamin B12", an immunoaffinity column containing monoclonal antibody with high affinity and specificity to vitamin B12. Subsequently, the vitamin B12 immunoaffinity column was washed with 10 ml water and the vitamin B12 was released from the column with 3 ml methanol. Following evaporation, the samples were reconstituted in mobile phase and analysed by HPLC-UV at 361 nm on an ACE 3AQ analytical column using a gradient elution consisting of 0.025% trifluoroacetic acid in water and acetonitrile. Analysis of three types of NIST Standard Reference Materials in triplicate demonstrated the results of the immunoaffinity column method were comparable to microbiological assay results. Method repeatability was determined for all samples analysed and ranged between 0.8 and 10%, demonstrating the method was repeatable with complex matrices (NIST 2383) containing low levels of vitamin B12 (0.44 microg per 100 g), as well as simpler matrices, such as vitamin tablets containing high levels (2000 microg per 0.849 g) of vitamin B12. PMID:19680900

Marley, E C; Mackay, E; Young, G



Tracing a roadmap for vitamin B12 testing using the health technology assessment approach.  


Abstract In our hospital, we are currently working to manage the appropriateness of vitamin B12 (B12) testing. Unfortunately, the classic evidence-based approach is unhelpful in this process and meta-analyzing data on the accuracy of this marker for cobalamin deficiency detection is misleading due to the lack of reference diagnostic methods. The approach currently proposed by the Health Technology Assessment (HTA) enables us to tackle the issue of B12 requests as a "healthcare" problem by considering the position of stakeholders involved in ordering, performing, interpreting the test, and receiving its results. Clinical expectations, methodological issues, and ethical aspects concerning the performance of the test can aid us in providing more guidance on the use of this marker. By building such structured information, hemodialysis patients and pregnant women have emerged as those groups preferentially requiring B12 testing, as it may potentially improve the clinical outcome. To avoid misinterpretation of B12 results more care should be taken in considering its biochemical and biological features, as well as the analytical issues. Spurious values obtained by current automated immunoassays may reflect suboptimal pre-analytical steps as well as known interfering conditions. Furthermore, the harmonization of results by available methods is still a far-reaching goal and the approach to interpret an individual's results should be improved. Tracing a roadmap for B12 testing by exploiting the HTA model to balance the stakeholders' claims and maximizing the patient's outcome may help to manage the marker demand. PMID:24304539

Ferraro, Simona; Mozzi, Roberta; Panteghini, Mauro



Theoretical analysis of electronic absorption spectra of vitamin B12 models  

NASA Astrophysics Data System (ADS)

Time-dependent density-functional theory (TD-DFT) is applied to analyze the electronic absorption spectra of vitamin B12. To accomplish this two model systems were considered: CN-[CoIII-corrin]-CN (dicyanocobinamide, DCC) and imidazole-[CoIII-corrin]-CN (cyanocobalamin, ImCC). For both models 30 lowest excited states were calculated together with transition dipole moments. When the results of TD-DFT calculations were directly compared with experiment it was found that the theoretical values systematically overestimate experimental data by approximately 0.5 eV. The uniform adjustment of the calculated transition energies allowed detailed analysis of electronic absorption spectra of vitamin B12 models. All absorption bands in spectral range 2.0-5.0 eV were readily assigned. In particular, TD-DFT calculations were able to explain the origin of the shift of the lowest absorption band caused by replacement of the-CN axial ligand by imidazole.

Andruniow, Tadeusz; Kozlowski, Pawel M.; Zgierski, Marek Z.



Development of a two-step cultivation strategy for the production of vitamin B12 by Bacillus megaterium  

PubMed Central

Background Vitamin B12 is a fascinating molecule which acts as a co-factor in the metabolism of many organisms, especially affecting DNA synthesis and regulation, fatty acid synthesis and energy production. The synthesis of vitamin B12 is limited to a few of bacteria and archaea. Therefore, industrial microbial fermentation is used to meet annual demands worldwide of vitamin B12 and as an alternative method to the chemical synthesis which requires at least 60 steps that is uneconomical. Bacillus megaterium is one of vitamin B12 producers and an ideal host for many biotechnology applications and being one of the best tools for the industrial production of several enzymes. Therefore, a two-step optimization strategy was established to produce high yield of vitamin B12 by B. megaterium through the provision of the production requirements and the suitable conditions for the biosynthesis of vitamin B12. Results We achieved the optimum conditions for the fermentation process of B. megaterium to produce high yield of vitamin B12 in a practical way based on statistical design and analysis which allowed vitamin B12 production to increase up to 759-fold (204.46 ?g/l) as compared with control without parameters (0.26 ?g/L). High performance liquid chromatography coupled to variable wavelength detector and mass spectrometry has been used to identify vitamin B12 forms and confirm the results. Conclusions We developed the fermentation process of B. megaterium to enhance the production of vitamin B12 by providing the required supplements for the synthesis of vitamin B12 (CoCl2, ?-aminolevulinic acid (ALA) and 5,6-dimethylbenzimidazole (DMB)) and dividing the fermentation process into three stages. In addition, the optimum incubation times of the three fermentation stages were investigated and performed with reducing number of experimental and evaluated multiple parameters and their interactions by using statistical experimental design and analysis. All of these strategies has proven successful in enhancing the production of vitamin B12 up to 204.46 ?g/l and demonstrated that B. megaterium could be a good candidate for the industrial production of vitamin B12.



Hyperhomocysteinemia, and low intakes of folic acid and vitamin B12 in urban North India  

Microsoft Academic Search

Summary  \\u000a Background and Aim An adverse coronary risk profile has been reported amongst rural-to-urban migrant population living in urban slums undergoing\\u000a stressful socio-economic transition. These individuals are likely to have low intakes of folic acid and vitamin B12, which\\u000a may have an adverse impact on serum levels of homocysteine (Hcy). To test this hypothesis, we studied serum levels of Hcy

Anoop Misra; Naval K. Vikram; R. M. Pandey; Manjari Dwivedi; Faiz Uddin Ahmad; Kalpana Luthra; Kajal Jain; Nidhi Khanna; J. Rama Devi; Rekha Sharma; Randeep Guleria



Effect of Vitamin B 12 and Folate on Homocysteine levels in colorectal cancer  

Microsoft Academic Search

Folate and cobalamin (Vitamin B12) are two essential micronutrients involved in one-carbon metabolism, which affects heart disease, neural tube defects and\\u000a cancer. Methylenetetrahydrofolate reductase, the key enzyme involved in one carbon metabolism produces methyl tetrahydrofolate\\u000a from methylene tetrahydrofolate, which in turn donates methyl group to homocysteine to generate methionine. There exist two\\u000a common low function polymorphic variants of the methylenetetrahydrofolate

Sunil Chandy; M. N. Sadananda Adiga; Girija Ramaswamy; C. Ramachandra; Lakshmi Krishnamoorthy



NMR-restrained molecular modeling of cobalt corrinoids: cyanocobalamin (vitamin B 12) and methylcobalt corrinoids  

Microsoft Academic Search

NMR-restrained molecular dynamics (MD) and simulated annealing (SA) calculations have been performed on cyanocobalamin (CNCbl, vitamin B12), and three methylcobalt corrinoids, the coenzymatically active methylcobalamin (CH3Cbl), and two analogs of its base-off species, methylcobinamide (CH3Cbi+), which lacks an axial nucleotide, and methyl-3,5,6-trimethyl-benzimidazolylcobamide (CH3Me3BzmCba+), in which the coordinating nitrogen of the pendent nucleotide is blocked by a methyl group. Consensus structures,

Kenneth L Brown; Xiang Zou; Helder M Marques



Iron and the folate-vitamin B12-methylation pathway in multiple sclerosis  

Microsoft Academic Search

Some subjects with multiple sclerosis (MS) present with low blood iron parameters. Anecdotal reports and a single patient\\u000a study suggest that iron supplementation may be beneficial in these subjects. Myelin is regenerated continually, but prerequisites\\u000a for this process are iron and a functional folate-vitamin B12-methylation pathway. The aim of this study was to determine\\u000a iron status, folate and homocysteine in

S. J. van Rensburg; M. J. Kotze; D. Hon; P. Haug; J. Kuyler; M. Hendricks; J. Botha; F. C. V. Potocnik; T. Matsha; R. T. Erasmus



Serum Levels of Zinc, Copper, Vitamin B12, Folate and Immunoglobulins in Individuals with Giardiasis  

PubMed Central

Background: Giardia lamblia is one of the most important intestinal parasites. The aim of this study was to measure serum levels of IgA, IgE, zinc, copper, vitamin B12 and folate in individuals with giardiasis in comparison to normal subjects. Methods: The study was carried out among 49 Giardia positive and 39 age and sex matched healthy volunteers. Examination of stool samples was done by direct wet smear and formol-ether concentration method. Serum samples were obtained for further laboratory examination. IgA levels were measured by Single Radial Immune Diffusion (SRID). IgE levels were measured by ELISA kit. Zinc and copper levels was measured by Ziestchem Diagnostics Kit and colorimetric endpoint-method respectively. Vitamin B12 and folate levels were measured by DRG Diagnostics Kit and Enzyme Immunoassay method respectively. All data were analyzed using SPSS version 17. Results: There was a statistically significant difference in IgA, IgE, copper and zinc levels between positive and negative groups (P<0.05). There was no significant difference between vitamin B12 and folate levels between the two groups. Mean values of Giardia positive and negative groups for IgA were 309.26 and 216.89 mg/dl, IgE 167.34 and 35.49 IU/ml, copper 309.74 and 253.61 ?g/dl and zinc 69.41 and 144.75 ?g/dl respectively. Conclusion: The results showed levels of IgA may correlate more closely with giardiasis than IgE. Regarding trace elements, giardiasis elevated serum copper levels, while it decreased serum zinc. Finally, there was no significant difference in serum levels of vitamin B12 and folic acid between the two groups.

Zarebavani, M; Dargahi, D; Einollahi, N; Dashti, N; Mohebali, M; Rezaeian, M



Folate, Vitamin B12, and Serum Total Homocysteine Levels in Confirmed Alzheimer Disease  

Microsoft Academic Search

Background: Recent studies suggest that vascular dis- ease may contribute to the cause of Alzheimer disease (AD). Since elevated plasma total homocysteine (tHcy) level is a risk factor for vascular disease, it may also be relevant to AD. Objective: To examine the association of AD with blood levels of tHcy, and its biological determinants folate and vitamin B12. Design: Case-control

Robert Clarke; A. David Smith; Kim A. Jobst; Helga Refsum; Lesley Sutton; Per M. Ueland



Serum Ferritin, Vitamin B 12 , Folate, and Zinc Levels in Children Infected with Helicobacter pylori  

Microsoft Academic Search

We sought to explore the relationship between Helicobacter pylori infection and serum ferritin, vitamin B12, folate, and zinc status among children. Fifty patients aged 5–18 years who underwent upper gastrointestinal endoscopy because\\u000a of dyspeptic symptoms, were studied, prospectively. Patients were grouped as H. pylori positive (group 1, n=32) or H. pylori negative (group 2, n=18) by histopathologic examination and rapid

Mustafa Akcam; Sebahat Ozdem; Aygen Yilmaz; Meral Gultekin; Reha Artan



Ultrafast electronic relaxation of excited state vitamin B 12 in the gas phase  

NASA Astrophysics Data System (ADS)

The time evolution of electronically excited vitamin B 12 (cyanocobalamin) has been observed for the first time in the gas phase. It reveals an ultrafast decay to a state corresponding to metal excitation. This decay is interpreted as resulting from a ring to metal electron transfer. This opens the observation of the excited state of other complex biomimetic systems in the gas phase, the key to the characterisation of their complex evolution through excited electronic states.

Shafizadeh, Niloufar; Poisson, Lionel; Soep, Beno?ˆt



Exploring novel modified vitamin B12 as a drug carrier: forecast from density functional theory modeling.  


Three non-native derivatives of vitamin B12 with imidazole, ethylenediamine, and pyrazine as cobalt(III) ?-ligands were characterized by applying the BP/def2-TZVP density functional method. The binding of all three ligands is thermodynamically favorable. It is proposed that their synthesis might be possible from aquacobalamin as a starting form of vitamin B12, as has been done in the case of an imidazole derivative of B12 (Hannibal et al. Inorg. Chem. 2007, 46, 3613-3618). Furthermore, the possibility of the formation of their conjugates with cisplatin is investigated. The proposed ?-ligands may serve as bridging ligands, binding to the platin ion as N-donors. In parallel, the calculations are done for the previously synthetized B12-cisplatin adduct with CN(-) as a bridging ligand and are compared with available experimental data, allowing assessment of the applied computational protocol. A good agreement between the computed and experimental structural parameters is obtained. In each of the studied structures, the Co-?-ligand bond is weaker than the Pt-?-ligand bond. PMID:23889131

Rutkowska-Zbik, Dorota; Mazur, Gabriela; Drzewiecka-Matuszek, Agnieszka; Orze?, ?ukasz; Stochel, Gra?yna



Disposable pencil graphite electrode modified with peptide nanotubes for Vitamin B12 analysis  

NASA Astrophysics Data System (ADS)

In this study, peptide nanostructures from diphenylalanine were synthesized in various solvents with various polarities and characterized with Scanning Electron Microscopy (SEM) and Powder X-ray Diffraction (PXRD) techniques. Formation of peptide nanofibrils, nanovesicles, nanoribbons, and nanotubes was observed in different solvent mediums. In order to investigate the effects of peptide nanotubes (PNT) on electrochemical behavior of disposable pencil graphite electrodes (PGE), electrode surfaces were modified with fabricated peptide nanotubes. Electrochemical activity of the pencil graphite electrode was increased with the deposition of PNTs on the surface. The effects of the solvent type, the peptide nanotube concentration, and the passive adsorption time of peptide nanotubes on pencil graphite electrode were studied. For further electrochemical studies, electrodes were modified for 30 min by immobilizing PNTs, which were prepared in water at 6 mg/mL concentration. Vitamin B12 analyses were performed by the Square Wave (SW) voltammetry method using modified PGEs. The obtained data showed linearity over the range of 0.2 ?M and 9.50 ?M Vitamin B12 concentration with high sensitivity. Results showed that PNT modified PGEs were highly simple, fast, cost effective, and feasible for the electro-analytical determination of Vitamin B12 in real samples.

Pala, Betül Bozdo?an; Vural, Tayfun; Kuralay, Filiz; Ç?rak, Tamer; Bolat, Gülçin; Abac?, Serdar; Denkba?, Emir Baki



Serum Asymmetric Dimethylarginine, Nitrate, Vitamin B12, and Homocysteine Levels in Individuals with Pulmonary Embolism  

PubMed Central

We aimed to analyze the pre- and posttreatment serum asymmetric dimethylarginine (ADMA), nitrate (NO3), vitamin B12 and homocysteine levels in pulmonary embolism (PTE) patients and to determine the prognostic value of these variables in predicting chronic thromboembolic pulmonary hypertension (CTEPH). This study was conducted in 64 patients. The patients were classified into the two groups: patients with normal pulmonary artery pressure (PAP) (group I) and patients with high PAP with persistent lung perfusion defects or who died at the end of 3 months of therapy (group II). We found statistically significant differences between two groups with respect to the partial oxygen pressure, the oxygen saturation, and the PAP, but there was no difference between the two groups with respect to the pretreatment ADMA, NO3, or homocysteine levels. The vitamin B12 levels were higher in group II. The NO3 levels increased and the ADMA and vitamin B12 levels decreased with treatment in both groups. These results suggest that these parameters are not predictive of the development of CTEPH.

Altuntas, Murat; Atalay, Figen; Can, Murat; Alt?n, Remzi; Tor, Meltem



Indicators for assessing folate and vitamin B-12 status and for monitoring the efficacy of intervention strategies123  

PubMed Central

Deficiencies of folate or of vitamin B-12 are widespread and constitute a major global burden of morbidity that affect all age groups. Detecting or confirming the presence of folate or vitamin B-12 deficiency and distinguishing one from the other depends, ultimately, on laboratory testing. Tests to determine the presence of folate or vitamin B-12 deficiency are used singly or in combination to establish the nutritional status and prevalence of deficiencies of the vitamins in various populations. The efficacy of interventions through the use of fortification or supplements is monitored by using the same laboratory tests. Tests currently in use have limitations that can be either technical or have a biological basis. Consequently, each single test cannot attain perfect sensitivity, specificity, or predictive value. Laboratory indicators of vitamin B-12 or folate status involve the measurement of either the total or a physiologically relevant fraction of the vitamin in a compartment such as blood. Thus, assays to measure vitamin B-12 or folate in plasma or serum as well as folate in red blood cells are in widespread use, and more recently, methods to measure vitamin B-12 associated with the plasma binding protein transcobalamin (holotranscobalamin) have been developed. Alternatively, concentrations of surrogate biochemical markers that reflect the metabolic function of the vitamin can be used. Surrogates most commonly used are plasma homocysteine, for detection of either vitamin B-12 or folate deficiency, and methylmalonic acid for detection of vitamin B-12 deficiency. The general methods as well as their uses, indications, and limitations are presented.

Green, Ralph



[Vitamin B12 deficiency associated with high doses od metformin in older people diabetic].  


Introduction: The aim of the study was to estimate if B12 deficiency is associated with the use of metformin in the elderly diabetics. Methods: Case-control study in diabetic OP. Cases (n = 137) were defined as elderly with B12 < 221 pmol/L and controls (n = 279) elderly with B12 > 221 pmol/L. Four categories of metformin use were defined: non-users, ??850 mg/day, > 850 and < 2,550 mg/day and ??2,550 mg/day. Metformin ??2,550 mg/day was high doses considered. The crude OR for B12 deficiency and consumption of Metformin were calculated. Logistic regression models were developed to explore the association between B12 deficiency and metformin dose. The research protocol was approved by the Ethics Committee of INTA. Results: The age of cases and controls was (70.2 years vs 68.6 years (p < 0.05). The 62% were women in cases vs 74.9% in controls (p < 0.05). The 73% of cases and 76% of controls used metformin (p < 0.05) the average consumption of metformin was de 1,954.3 mg/day (SD: 1,063.2) in cases and 1,696.6 mg/day (SD: 1,074.4) in controls (p < 0.05). The use of 2,550 mg/day was observed in 29.2% of cases and 19.3% for controls (p < 0.05). It was observed that OP who consumed high doses of metformin had 1.9 times the risk of B12 deficiency (OR: 1.9; 95%CI: 1,08- 3,30). Conclusion: These results show a strong association between high doses of metformin and low levels of vitamin B12 in diabetic elderly. This project was funded by FONIS SA11I2092. PMID:24972480

Sánchez, Hugo; Masferrer, Dominique; Lera, Lydia; Arancibia, Estrella; Angel, Barbara; Albala, Cecilia



Imbalance of folic acid and vitamin B12 is associated with birth outcome: an Indian pregnant women study.  


Background/objectives:Maternal nutrient supplementation in developing countries is generally restricted to provision of iron and folic acid. Along with folic acid, vitamin B12 is also an important determinant of fetal growth and development. During pregnancy, the increased requirement of folic acid is met with supplementation, while vitamin B12 remains untreated and possibly deficient. The objective of our study was to study the combined effect of maternal plasma folate and vitamin B12, and their ratio on birth anthropometrics.Subjects/methods:We carried out an observational study on 49 full-term pregnant women at KEM Hospital, Pune, India, during 2006-2008, and measured plasma folate, vitamin B12 and homocysteine in venous blood at 36 weeks of gestation. Neonatal anthropometrics (birth weight, length, head circumference, abdominal circumference, mid arm circumference, chest circumference, triceps skinfold and subscapular skinfold thickness) were measured within 24?h of birth.Results:Maternal plasma folate and vitamin B12 were not correlated to neonatal anthropometrics. The combined association of folate and vitamin B12 expressed as folate to vitamin B12 ratio was correlated to the neonatal anthropometrics. Imbalance in the maternal micronutrients with increasing ratio of folate to vitamin B12 was associated with an increase in plasma homocysteine (P=0.014), lowering of neonatal birth weight (P=0.009), birth length (P=0.034), head circumference (P=0.018) and chest circumference (P=0.009), while no significant association to other anthropometrics was observed.Conclusions:Supplementation of vitamin B12 in addition to supplementation of folic acid in pregnancy may be important for improving birth weight, birth length, head circumference and chest circumference. PMID:24448492

Gadgil, M; Joshi, K; Pandit, A; Otiv, S; Joshi, R; Brenna, J T; Patwardhan, B



Oral vitamin B12 for patients suspected of subtle cobalamin deficiency: a multicentre pragmatic randomised controlled trial  

PubMed Central

Background Evidence regarding the effectiveness of oral vitamin B12 in patients with serum vitamin B12 levels between 125-200 pM/l is lacking. We compared the effectiveness of one-month oral vitamin B12 supplementation in patients with a subtle vitamin B12 deficiency to that of a placebo. Methods This multicentre (13 general practices, two nursing homes, and one primary care center in western Switzerland), parallel, randomised, controlled, closed-label, observer-blind trial included 50 patients with serum vitamin B12 levels between 125-200 pM/l who were randomized to receive either oral vitamin B12 (1000 ?g daily, N = 26) or placebo (N = 24) for four weeks. The institution's pharmacist used simple randomisation to generate a table and allocate treatments. The primary outcome was the change in serum methylmalonic acid (MMA) levels after one month of treatment. Secondary outcomes were changes in total homocysteine and serum vitamin B12 levels. Blood samples were centralised for analysis and adherence to treatment was verified by an electronic device (MEMS; Aardex Europe, Switzerland). Trial registration: ISRCTN 22063938. Results Baseline characteristics and adherence to treatment were similar in both groups. After one month, one patient in the placebo group was lost to follow-up. Data were evaluated by intention-to-treat analysis. One month of vitamin B12 treatment (N = 26) lowered serum MMA levels by 0.13 ?mol/l (95%CI 0.06-0.19) more than the change observed in the placebo group (N = 23). The number of patients needed to treat to detect a metabolic response in MMA after one month was 2.6 (95% CI 1.7-6.4). A significant change was observed for the B12 serum level, but not for the homocysteine level, hematocrit, or mean corpuscular volume. After three months without active treatment (at four months), significant differences in MMA levels were no longer detected. Conclusions Oral vitamin B12 treatment normalised the metabolic markers of vitamin B12 deficiency. However, a one-month daily treatment with1000 ?g oral vitamin B12 was not sufficient to normalise the deficiency markers for four months, and treatment had no effect on haematological signs of B12 deficiency.



Genetic Architecture of Vitamin B12 and Folate Levels Uncovered Applying Deeply Sequenced Large Datasets  

PubMed Central

Genome-wide association studies have mainly relied on common HapMap sequence variations. Recently, sequencing approaches have allowed analysis of low frequency and rare variants in conjunction with common variants, thereby improving the search for functional variants and thus the understanding of the underlying biology of human traits and diseases. Here, we used a large Icelandic whole genome sequence dataset combined with Danish exome sequence data to gain insight into the genetic architecture of serum levels of vitamin B12 (B12) and folate. Up to 22.9 million sequence variants were analyzed in combined samples of 45,576 and 37,341 individuals with serum B12 and folate measurements, respectively. We found six novel loci associating with serum B12 (CD320, TCN2, ABCD4, MMAA, MMACHC) or folate levels (FOLR3) and confirmed seven loci for these traits (TCN1, FUT6, FUT2, CUBN, CLYBL, MUT, MTHFR). Conditional analyses established that four loci contain additional independent signals. Interestingly, 13 of the 18 identified variants were coding and 11 of the 13 target genes have known functions related to B12 and folate pathways. Contrary to epidemiological studies we did not find consistent association of the variants with cardiovascular diseases, cancers or Alzheimer's disease although some variants demonstrated pleiotropic effects. Although to some degree impeded by low statistical power for some of these conditions, these data suggest that sequence variants that contribute to the population diversity in serum B12 or folate levels do not modify the risk of developing these conditions. Yet, the study demonstrates the value of combining whole genome and exome sequencing approaches to ascertain the genetic and molecular architectures underlying quantitative trait associations.

Thorleifsson, Gudmar; Ahluwalia, Tarunveer S.; Steinthorsdottir, Valgerdur; Bjarnason, Helgi; Gudbjartsson, Daniel F.; Magnusson, Olafur T.; Spars?, Thomas; Albrechtsen, Anders; Kong, Augustine; Masson, Gisli; Tian, Geng; Cao, Hongzhi; Nie, Chao; Kristiansen, Karsten; Husemoen, Lise Lotte; Thuesen, Betina; Li, Yingrui; Nielsen, Rasmus; Linneberg, Allan; Olafsson, Isleifur; Eyjolfsson, Gudmundur I.; J?rgensen, Torben; Wang, Jun; Hansen, Torben; Thorsteinsdottir, Unnur; Stefansson, Kari; Pedersen, Oluf




PubMed Central

Vitamin B12 deficiency is emerging as a growing public health problem. The most commonly used diagnostic tests are limited in accuracy, sensitivity, and are non-specific for B12 deficiency. The aim of this study was to develop a simple B12 Breath Test (BBT) to more accurately evaluate vitamin B12 status as an alternative to the most common diagnostic test, serum B12 levels. The breath test is based on the metabolism of sodium 1-13C-propionate to 13CO2 which requires B12 as a cofactor. We initially compared the BBT to current B12 diagnostic methods in 58 subjects. Subjects also received a second BBT 1–3 days after initial testing to evaluate reproducibility of results. Propionate dosage, fasting times, and collection periods were compared respectively. The dose of sodium 1-13C-propionate (10 to 50 mg) gave equivalent results while an 8 hour fast was essential. Statistical analysis revealed that breath collection times could be reduced to just a baseline and 10 and 20 minutes following propionate dosing. We also measured the incidence of B12 deficiency with the BBT in 119 patients with chronic pancreatitis, Crohn’s disease, small intestinal bacterial overgrowth, and subjects over 65 years of age. The BBT results agreed with previous publications showing a higher incidence of B12 deficiency in these patients. The BBT may provide clinicians with a non-invasive, accurate, reliable, and reproducible diagnostic test to detect vitamin B12 deficiency.

Wagner, David A.; Schatz, Richard; Coston, Richard; Curington, Cheryl; Bolt, Daniel; Toskes, Phillip P.



Surface-enhanced Raman spectroscopy of Vitamin B 12 on silver particles in colloid and in atmosphere  

NASA Astrophysics Data System (ADS)

The surface-enhanced Raman scattering (SERS) spectra of Vitamin B 12 molecules on silver surface in colloid and in atmosphere were obtained with very low laser power. The SERS on silver surface in atmosphere shows more intense enhancement with sharper and narrower Raman peaks compared with the SERS in colloid. The adsorption geometries of Vitamin B 12 molecules were analyzed based on the SERS data. Vitamin B 12 molecule is supposed to adsorb on the silver particle in colloid with the corrin ring plane nearly vertical to the surface, while Vitamin B 12 molecule is supposed to adsorb on silver surface with the corrin ring plane tilted to the surface. This could be due to the water effect of the molecular conformation and the characteristic of silver particles.

Zhang, Zhenlong; Wang, Bo; Yin, Yanfeng; Mo, Yujun



Control of vitamin B 12 release from poly(ethylene glycol)\\/poly(butylene terephthalate) multiblock copolymers  

Microsoft Academic Search

The release of vitamin B12 (1355Da) from matrices based on multiblock copolymers was studied. The copolymers were composed of hydrophilic poly(ethylene glycol)-terephthalate (PEGT) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks. Vitamin B12 loaded films were prepared by using a water-in-oil emulsion method. The copolymer properties, like permeability, could be varied by increasing the PEG-segment length from 300 up to 4000g\\/mol

R. van Dijkhuizen-Radersma; F. L. A. M. A. Péters; N. A. Stienstra; D. W. Grijpma; J. Feijen; K. de Groot; J. M. Bezemer



Methyl-transfer reaction to alkylthiol catalyzed by a simple vitamin B 12 model complex using zinc powder  

Microsoft Academic Search

The catalytic methyl-transfer reaction from methyl tosylate to 1-octanethiol was carried out in the presence of a simple vitamin B12 model complex, [Co(III){(C2C3)(DO)(DOH)pn}Br2], with zinc powder as the reducing reagent at 50°C. Such a catalytic reaction proceeded via the formation and dissociation of a cobalt–carbon bond in the simple vitamin B12 model complex under non-enzymatic conditions. The mechanism for the

Ling Pan; Keishiro Tahara; Takahiro Masuko; Yoshio Hisaeda



Vitamin B12 Is a Strong Determinant of Low Methionine Synthase Activity and DNA Hypomethylation in Gastrectomized Rats  

Microsoft Academic Search

Background\\/Aims: The respective influence of folate and vitamin B12 deficiency on MTR activity and transcription, and on DNA methylation is not clearly established. The aim of this study was to assess the respective influence of folate and vitamin B12 deficiency on MTR transcription and activity, and on DNA methylation. Methods: Sixty-one rats were administered normal diet or diet deficient in

Laurent Brunaud; Jean-Marc Alberto; Ahmet Ayav; Philippe Gérard; Farès Namour; Laurent Antunes; Marc Braun; Jean-Pierre Bronowicki; Laurent Bresler; Jean-Louis Guéant



Helicobacter pylori infection does not influence the efficacy of iron and vitamin B12 fortification in marginally nourished Indian children  

Microsoft Academic Search

Background\\/Objectives:Helicobacter pylori infection and iron and vitamin B12 deficiencies are widespread in economically disadvantaged populations. There is emerging evidence that H. pylori infection has a negative effect on the absorption of these micronutrients. The aim of this study was to evaluate the effect of H. pylori infection on the efficacy of micronutrient (including iron and vitamin B12)-fortified foods supplied for

P Thankachan; S Muthayya; A Sierksma; A Eilander; T Thomas; G S Duchateau; L G J Frenken; A V Kurpad



The influence of iron, vitamin B 12, and folate levels on soluble transferrin receptor concentration in pregnant women  

Microsoft Academic Search

Background: Soluble transferrin receptor (sTfR) concentration is high in iron deficiency and in conditions of increased erythropoiesis. In developing countries like Brazil, pregnant women usually have concurrent iron, vitamin B12, and folate deficiencies. This study investigated the relationship between serum sTfR concentration and iron, vitamin B12, and folate status in pregnant women. Methods: The concentration of the sTfR, hematocrit (Hct),

Adriana de Azevedo Paiva; Patr??cia H. C. Rondó; Elvira M. Guerra-Shinohara; Camila S. Silva



Release of toxic Gd3+ ions to tumour cells by vitamin B12 bioconjugates.  


Two probes consisting of vitamin B(12) (CNCbl) conjugated to Gd chelates by esterification of the ribose 5'-OH moiety, Gd-DTPA-CNCbl (1; DTPA = diethylenetriamine-N,N,N',N'',N''-pentaacetic acid) and Gd-TTHA-CNCbl (2; TTHA = triethylenetetramine-N,N,N',N'',N''',N'''-hexaacetic acid), have been synthesised and characterised. The crystal structure of a dimeric form of 1, obtained by crystallisation with an excess of GdCl(3), has been determined. The kinetics of binding to and dissociation from transcobalamin II show that 1 and 2 maintain high-affinity binding to the vitamin B(12) transport protein. Complex 2 is very stable with respect to Gd(3+) release owing to the saturated co-ordination of the Gd(3+) ion by four amino and five carboxylate groups. Hydrolysis of the ester functionality occurs on the time scale of several hours. The lack of saturation and the possible involvement of the ester functionality in co-ordination result in lower stability of 1 towards hydrolysis and in a considerable release of Gd(3+) in vitro. Gd(3+) ions released from 1 are avidly taken up by the K562 tumour cells to an extent corresponding to approximately 10(10) Gd(3+) per cell. The internalisation of toxic Gd(3+) ions causes a marked decrease in cell viability as assessed by Trypan blue and WST-1 tests. On the contrary, the experiments with the more stable 2 did not show any significant cell internalisation of Gd(3+) ions and any influence on cell viability. The results point to new avenues of in situ generation of cytotoxic pathways based on the release of toxic Gd(3+) ions by vitamin B(12) bioconjugates. PMID:19562781

Siega, Patrizia; Wuerges, Jochen; Arena, Francesca; Gianolio, Eliana; Fedosov, Sergey N; Dreos, Renata; Geremia, Silvano; Aime, Silvio; Randaccio, Lucio



Simultaneous determination of vitamin B12 and its derivatives using some of multivariate calibration 1 (MVC1) techniques  

NASA Astrophysics Data System (ADS)

Resolution of binary mixtures of vitamin B12, methylcobalamin and B12 coenzyme with minimum sample pre-treatment and without analyte separation has been successfully achieved by methods of partial least squares algorithm with one dependent variable (PLS1), orthogonal signal correction/partial least squares (OSC/PLS), principal component regression (PCR) and hybrid linear analysis (HLA). Data of analysis were obtained from UV-vis spectra. The UV-vis spectra of the vitamin B12, methylcobalamin and B12 coenzyme were recorded in the same spectral conditions. The method of central composite design was used in the ranges of 10-80 mg L -1 for vitamin B12 and methylcobalamin and 20-130 mg L -1 for B12 coenzyme. The models refinement procedure and validation were performed by cross-validation. The minimum root mean square error of prediction (RMSEP) was 2.26 mg L -1 for vitamin B12 with PLS1, 1.33 mg L -1 for methylcobalamin with OSC/PLS and 3.24 mg L -1 for B12 coenzyme with HLA techniques. Figures of merit such as selectivity, sensitivity, analytical sensitivity and LOD were determined for three compounds. The procedure was successfully applied to simultaneous determination of three compounds in synthetic mixtures and in a pharmaceutical formulation.

Samadi-Maybodi, Abdolraouf; Darzi, S. K. Hassani Nejad



Increases in Plasma Holotranscobalamin Can Be Used to Assess Vitamin B-12 Absorption in Individuals with Low Plasma Vitamin B-12123  

PubMed Central

Low plasma concentrations of vitamin B-12 are common in Indians, possibly due to low dietary intakes of animal-source foods. Weather malabosrption of the vitamin contributes to this has not been investigated. A rise in plasma holotranscobalamin (holo-TC) concentration after a standard dose of oral vitamin B-12 has been proposed as a measure of gastrointestinal absorption in people with normal plasma vitamin B-12 concentrations. We studied 313 individuals (children and parents, 109 families) in the Pune Maternal Nutrition Study. They received 3 doses of 10 ?g (n=191) or 2 ?g (n=122) of cyanocobalamin at 6 h intervals. A rise in plasma holo-TC of ?15% and >15 pmol/L above baseline was considered normal vitamin B-12 absorption. The baseline plasma vitamin B-12 was <150 pmol/L in 48% of participants; holo-TC was <35 pmol/L in 98%, and total homocysteine was high in 50% (>10 ?mol/L in children and >15 ?mol/L in adults). In 10 ?g group plasma holo-TC concentration increased by 4.8 -fold from (mean ± SD) 9.3 ± 7.0 pmol/L to 53.8 ± 25.9 pmol/L, and in 2 ?g group by 2.2 -fold from 11.1 ± 8.5 pmol/L to 35.7 ± 19.3 pmol/L. Only 10% of participants, mostly fathers, had an increase less than the suggested cut-points. Our results suggest that an increase in plasma holo-TC may be used to assess vitamin B-12 absorption in individuals with low vitamin B-12 status. Because malabsorption is unlikely to be a major reason for the low plasma vitamin B-12 concentrations in this population, increasing dietary vitamin B-12 should improve their status.

Bhat, Dattatray S.; Thuse, Nileema V.; Lubree, Himangi G.; Joglekar, Charudatta V.; Naik, Sadanand S.; Ramdas, Lalita V.; Johnston, Carole; Refsum, Helga; Fall, Caroline H.; Yajnik, Chittaranjan S.



Microbiological assay for vitamin B12 performed in 96-well microtitre plates.  

PubMed Central

A simplified microbiological assay for vitamin B12 estimation, completed on microtitre plates using a colistin sulphate resistant strain of Lactobacillus leichmannii (NCIB 12519), and cryopreserved cultures is described. The new assay correlated well with a more conventional "tube" assay and was not influenced by the presence of antibiotics in serum. Evaluation of assay performance showed excellent interassay and intra-assay precision with quantitative recovery of added cyanocobalamin over a wide range of additions (94.9%-102.1%). The advantages of short incubation time, easy reading, and minimal reagent costs make this assay an attractive option in the routine clinical laboratory and in research.

Kelleher, B P; Broin, S D



Reductive dechlorination of a polychlorinated biphenyl congener and hexachlorobenzene by vitamin B12.  

PubMed Central

The polychlorinated biphenyl congener 2,3,4,5,6-pentachlorobiphenyl and hexachlorobenzene were reductively dechlorinated in an aqueous biomimetic model system containing vitamin B12. The products of 2,3,4,5,6-pentachlorobiphenyl dechlorination were 2,3,5,6- and 2,3,4,6-tetrachlorobiphenyl. Hexachlorobenzene dechlorinated to pentachlorobenzene and a mixture of 1,2,4,5- and 1,2,3,5-tetrachlorobenzene. The proton from water was shown to be the source of the hydrogen atom used for the replacement of chlorine on the biphenyl ring.

Assaf-Anid, N; Nies, L; Vogel, T M



Discovery of Novel Sources of Vitamin B12 in Traditional Korean Foods from Nutritional Surveys of Centenarians  

PubMed Central

Human longevity can be explained by a variety of factors, among them, nutritional factor would play an important role. In our study of Korean centenarians for their longevity, the apparent nutritional imbalance in the traditional semi-vegetarian diet raised a special attention, especially on vitamin B12 status, supplied by animal foods. Interestingly, we found that the prevalence of vitamin B12 deficient Korean centenarians was not higher compared with those from Western nations with animal-oriented traditional foods. We assumed that there might be some unveiled sources for vitamin B12 in the Korean traditional foods. Screening of vitamin B12 contents has revealed that some traditional soybean-fermented foods, such as Doenjang and Chunggukjang, and seaweeds contain considerable amounts of vitamin B12. Taken together, it can be summarized that the traditional foods, especially of fermentation, might be evaluated for compensation of the nutritional imbalance in the vegetable-oriented dietary pattern by supplying vitamin B12, resulting in maintenance of health status.

Kwak, Chung Shil; Lee, Mee Sook; Oh, Se In; Park, Sang Chul



Comparative genomic analyses of nickel, cobalt and vitamin B12 utilization  

PubMed Central

Background Nickel (Ni) and cobalt (Co) are trace elements required for a variety of biological processes. Ni is directly coordinated by proteins, whereas Co is mainly used as a component of vitamin B12. Although a number of Ni and Co-dependent enzymes have been characterized, systematic evolutionary analyses of utilization of these metals are limited. Results We carried out comparative genomic analyses to examine occurrence and evolutionary dynamics of the use of Ni and Co at the level of (i) transport systems, and (ii) metalloproteomes. Our data show that both metals are widely used in bacteria and archaea. Cbi/NikMNQO is the most common prokaryotic Ni/Co transporter, while Ni-dependent urease and Ni-Fe hydrogenase, and B12-dependent methionine synthase (MetH), ribonucleotide reductase and methylmalonyl-CoA mutase are the most widespread metalloproteins for Ni and Co, respectively. Occurrence of other metalloenzymes showed a mosaic distribution and a new B12-dependent protein family was predicted. Deltaproteobacteria and Methanosarcina generally have larger Ni- and Co-dependent proteomes. On the other hand, utilization of these two metals is limited in eukaryotes, and very few of these organisms utilize both of them. The Ni-utilizing eukaryotes are mostly fungi (except saccharomycotina) and plants, whereas most B12-utilizing organisms are animals. The NiCoT transporter family is the most widespread eukaryotic Ni transporter, and eukaryotic urease and MetH are the most common Ni- and B12-dependent enzymes, respectively. Finally, investigation of environmental and other conditions and identity of organisms that show dependence on Ni or Co revealed that host-associated organisms (particularly obligate intracellular parasites and endosymbionts) have a tendency for loss of Ni/Co utilization. Conclusion Our data provide information on the evolutionary dynamics of Ni and Co utilization and highlight widespread use of these metals in the three domains of life, yet only a limited number of user proteins.

Zhang, Yan; Rodionov, Dmitry A; Gelfand, Mikhail S; Gladyshev, Vadim N



Oral versus intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency: a pragmatic, randomised, multicentre, non-inferiority clinical trial undertaken in the primary healthcare setting (Project OB12)  

PubMed Central

Background The oral administration of vitamin B12 offers a potentially simpler and cheaper alternative to parenteral administration, but its effectiveness has not been definitively demonstrated. The following protocol was designed to compare the effectiveness of orally and intramuscularly administered vitamin B12 in the treatment of patients ≥65 years of age with vitamin B12 deficiency. Methods/design The proposed study involves a controlled, randomised, multicentre, parallel, non-inferiority clinical trial lasting one year, involving 23 primary healthcare centres in the Madrid region (Spain), and patients ≥65 years of age. The minimum number of patients required for the study was calculated as 320 (160 in each arm). Bearing in mind an estimated 8-10% prevalence of vitamin B12 deficiency among the population of this age group, an initial sample of 3556 patients will need to be recruited. Eligible patients will be randomly assigned to one of the two treatment arms. In the intramuscular treatment arm, vitamin B12 will be administered as follows: 1 mg on alternate days in weeks 1 and 2, 1 mg/week in weeks 3–8,and 1 mg/month in weeks 9–52. In the oral arm, the vitamin will be administered as: 1 mg/day in weeks 1–8 and 1 mg/week in weeks 9–52. The main outcome variable to be monitored in both treatment arms is the normalisation of the serum vitamin B12 concentration at weeks 8, 26 and 52; the secondary outcome variables include the serum concentration of vitamin B12 (in pg/ml), adherence to treatment, quality of life (EuroQoL-5D questionnaire), patient 3satisfaction and patient preferences. All statistical tests will be performed with intention to treat and per protocol. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in analyses. Discussion The results of this study should help establish, taking quality of life into account, whether the oral administration of vitamin B12 is an effective alternative to its intramuscular administration. If this administration route is effective, it should provide a cheaper means of treating vitamin B12 deficiency while inducing fewer adverse effects. Having such an alternative would also allow patient preferences to be taken into consideration at the time of prescribing treatment. Trial registration This trial has been registered with, number NCT 01476007, and under EUDRACT number 2010-024129-20.



Influence of heme and vitamin B12 on growth and fermentations of Bacteroides species.  

PubMed Central

We examined the effects of heme on the growth and fermentations of Bacteroides species. Bacteroides fragilis ATCC 25285 required heme for growth and produced malate and lactate as major products of glucose fermentation when the concentration of heme was 1 ng/ml. With 1 microgram of heme per ml, malate was not formed, lactate production decreased, and succinate and acetate were the major fermentation products. B. eggerthii ATCC 27754 grew without heme, with the production of mainly malate and lactate from glucose. Its fermentation with 1 microgram of heme per ml was similar to that of B. fragilis grown with the same concentration of heme. B. splanchicus VPI 6842 grew without heme, with the production of mainly malate, acetate, and H2 from glucose. With 1 microgram of heme per ml, malate disappeared, H2 decreased significantly, and succinate, acetate, and butyrate were the major products. The addition of vitamin B12 to media containing 1 microgram of heme per ml caused all species to produce propionate at the expense of succinate and, with B. splanchnicus, also at the expense of butyrate. Thus, the concentration of heme and the presence of vitamin B12 significantly influenced the course of glucose fermentation by these bacteria.

Chen, M; Wolin, M J



Unusual mitochondria in the hepatocytes of rats treated with a vitamin B12 analogue.  


Adult male rats were administered hydroxy-cobalamin (c-lactam) (HCCL), a vitamin B12 analogue, by means of osmotic mini-pumps. The metabolic effects of HCCL are similar to those produced by simple dietary deficiency of vitamin B12 (Frenkel et al., 1976), but the morphological alterations in hepatic mitochondria are quite different in the two treatments. In HCCL-treated animals, hepatic mitochondria showed significant increases in number. In one rat, the hepatic mitochondria frequently had a single, elongated, circumferentially-oriented crista, with the inner compartment being occupied by a greatly augmented matrix. Such organelles appeared to be capable of division, as indicated by medially-partitioned forms. Numerous hooded mitochondria were present in the hepatic cells of the same animal. Almost every mitochondrion of whatever morphology was partially or completely shrouded by a cistern of rough endoplasmic reticulum. These mitochondrial morphological changes may be related to the chronic metabolic changes in this animal model of methylmalonic aciduria. PMID:1661107

Tandler, B; Krahenbuhl, S; Brass, E P



Characterization of the cobalamin (vitamin B12) biosynthetic genes of Salmonella typhimurium.  


Salmonella typhimurium synthesizes cobalamin (vitamin B12) de novo under anaerobic conditions. Of the 30 cobalamin synthetic genes, 25 are clustered in one operon, cob, and are arranged in three groups, each group encoding enzymes for a biochemically distinct portion of the biosynthetic pathway. We have determined the DNA sequence for the promoter region and the proximal 17.1 kb of the cob operon. This sequence includes 20 translationally coupled genes that encode the enzymes involved in parts I and III of the cobalamin biosynthetic pathway. A comparison of these genes with the cobalamin synthetic genes from Pseudomonas denitrificans allows assignment of likely functions to 12 of the 20 sequenced Salmonella genes. Three additional Salmonella genes encode proteins likely to be involved in the transport of cobalt, a component of vitamin B12. However, not all Salmonella and Pseudomonas cobalamin synthetic genes have apparent homologs in the other species. These differences suggest that the cobalamin biosynthetic pathways differ between the two organisms. The evolution of these genes and their chromosomal positions is discussed. PMID:8501034

Roth, J R; Lawrence, J G; Rubenfield, M; Kieffer-Higgins, S; Church, G M



Structural basis of multifunctionality in a vitamin B12-processing enzyme.  


An early step in the intracellular processing of vitamin B(12) involves CblC, which exhibits dual reactivity, catalyzing the reductive decyanation of cyanocobalamin (vitamin B(12)), and the dealkylation of alkylcobalamins (e.g. methylcobalamin; MeCbl). Insights into how the CblC scaffold supports this chemical dichotomy have been unavailable despite it being the most common locus of patient mutations associated with inherited cobalamin disorders that manifest in both severe homocystinuria and methylmalonic aciduria. Herein, we report structures of human CblC, with and without bound MeCbl, which provide novel biochemical insights into its mechanism of action. Our results reveal that CblC is the most divergent member of the NADPH-dependent flavin reductase family and can use FMN or FAD as a prosthetic group to catalyze reductive decyanation. Furthermore, CblC is the first example of an enzyme with glutathione transferase activity that has a sequence and structure unrelated to the GST superfamily. CblC thus represents an example of evolutionary adaptation of a common structural platform to perform diverse chemistries. The CblC structure allows us to rationalize the biochemical basis of a number of pathological mutations associated with severe clinical phenotypes. PMID:21697092

Koutmos, Markos; Gherasim, Carmen; Smith, Janet L; Banerjee, Ruma



Impact of Vitamin B12 on Formation of the Tetrachloroethene Reductive Dehalogenase in Desulfitobacterium hafniense Strain Y51  

PubMed Central

Corrinoids are essential cofactors of reductive dehalogenases in anaerobic bacteria. Microorganisms mediating reductive dechlorination as part of their energy metabolism are either capable of de novo corrinoid biosynthesis (e.g., Desulfitobacterium spp.) or dependent on exogenous vitamin B12 (e.g., Dehalococcoides spp.). In this study, the impact of exogenous vitamin B12 (cyanocobalamin) and of tetrachloroethene (PCE) on the synthesis and the subcellular localization of the reductive PCE dehalogenase was investigated in the Gram-positive Desulfitobacterium hafniense strain Y51, a bacterium able to synthesize corrinoids de novo. PCE-depleted cells grown for several subcultivation steps on fumarate as an alternative electron acceptor lost the tetrachloroethene-reductive dehalogenase (PceA) activity by the transposition of the pce gene cluster. In the absence of vitamin B12, a gradual decrease of the PceA activity and protein amount was observed; after 5 subcultivation steps with 10% inoculum, more than 90% of the enzyme activity and of the PceA protein was lost. In the presence of vitamin B12, a significant delay in the decrease of the PceA activity with an ?90% loss after 20 subcultivation steps was observed. This corresponded to the decrease in the pceA gene level, indicating that exogenous vitamin B12 hampered the transposition of the pce gene cluster. In the absence or presence of exogenous vitamin B12, the intracellular corrinoid level decreased in fumarate-grown cells and the PceA precursor formed catalytically inactive, corrinoid-free multiprotein aggregates. The data indicate that exogenous vitamin B12 is not incorporated into the PceA precursor, even though it affects the transposition of the pce gene cluster.

Reinhold, Anika; Westermann, Martin; Seifert, Jana; von Bergen, Martin; Schubert, Torsten



Deficiencies of the Microelements, Folate and Vitamin B12 in Women of the Child Bearing Ages in Gorgan, Northern Iran  

PubMed Central

Background: The deficiencies of folic acid, vitamin B12, and microelements during pregnancy may affect the health of newborns. Objectives: To assess the serum levels of folate, vitamin B12, iron, zinc and copper in healthy women of the childbearing ages in Gorgan, northern Iran. Methodology: This descriptive, cross-sectional study was carried out on 100 women of childbearing ages in northern Iran during November 2007-March 2008. The serum levels of folate, vitamin B12, iron, copper and zinc were evaluated by laboratory tests. Results: Iron, copper , folate, vitamin B12 deficiencies and folate with vitamin B12 deficiency were detected in 13%, 32% , 13% , 32% and 11% women of the childbearing ages, respectively . According to the ethnicity, vitamin B12, folate and iron deficiencies in the Sistani group were observed in 38.3%, 12.9% and 12.9% of the women, respectively. In the native Fars group, the above mentioned deficiencies were found in 31.1%, 13.4% and 7.5% of the subjects. Folate and vitamin B12 deficiencies were observed in the urban habitant in 32.7% and 11.5 % of the subjects as compared to those in the rural habitant (in 30.4% and 15.2%of the subjects respectively). The folate deficiencies in the under and above 18 years old subjects were 22.2% and 9.9%, respectively. Conclusions: This study showed that the deficiency of the micronutrients was considerable in women of the childbearing ages in Gorgan, northern Iran.

Sedehi, Maliheh; Behnampour, Naser; Golalipour, Mohammad Jafar



Deficiencies of the microelements, folate and vitamin B12 in women of the child bearing ages in gorgan, northern iran.  


Background: The deficiencies of folic acid, vitamin B12, and microelements during pregnancy may affect the health of newborns. Objectives: To assess the serum levels of folate, vitamin B12, iron, zinc and copper in healthy women of the childbearing ages in Gorgan, northern Iran. Methodology: This descriptive, cross-sectional study was carried out on 100 women of childbearing ages in northern Iran during November 2007-March 2008. The serum levels of folate, vitamin B12, iron, copper and zinc were evaluated by laboratory tests. Results: Iron, copper , folate, vitamin B12 deficiencies and folate with vitamin B12 deficiency were detected in 13%, 32% , 13% , 32% and 11% women of the childbearing ages, respectively . According to the ethnicity, vitamin B12, folate and iron deficiencies in the Sistani group were observed in 38.3%, 12.9% and 12.9% of the women, respectively. In the native Fars group, the above mentioned deficiencies were found in 31.1%, 13.4% and 7.5% of the subjects. Folate and vitamin B12 deficiencies were observed in the urban habitant in 32.7% and 11.5 % of the subjects as compared to those in the rural habitant (in 30.4% and 15.2%of the subjects respectively). The folate deficiencies in the under and above 18 years old subjects were 22.2% and 9.9%, respectively. Conclusions: This study showed that the deficiency of the micronutrients was considerable in women of the childbearing ages in Gorgan, northern Iran. PMID:23905113

Sedehi, Maliheh; Behnampour, Naser; Golalipour, Mohammad Jafar



AMN Directs Endocytosis of the Intrinsic Factor-Vitamin B12 Receptor Cubam by Engaging ARH or Dab2  

PubMed Central

Cubam is a multi-ligand receptor involved in dietary uptake of intrinsic factor-vitamin B12 in the small intestine and reabsorption of various low-molecular-weight proteins (such as albumin, transferrin, apolipoprotein A-I and vitamin D-binding protein) in the kidney. Cubam is composed of two proteins: cubilin and amnionless. Cubilin harbors ligand binding capabilities, while amnionless provides membrane anchorage and potential endocytic capacity via two FXNPXF signals within the cytosolic domain. These signals are similar to the FXNPXY signals found in members of the low-density lipoprotein receptor superfamily, which associate with clathrin-associated sorting proteins, including Disabled-2 (Dab2) and autosomal recessive hypercholesterolemia (ARH), during endocytosis. We therefore investigated the functionality of each amnionless FXNPXF signal and their respective interaction with sorting proteins. By sequential mutation and expression of a panel of amnionless mutants combined with yeast two-hybrid analyses, we demonstrate that the signals are functionally redundant and both are able to mediate endocytosis of cubam through interaction with Dab2 and ARH.

Pedersen, Gitte Albinus; Chakraborty, Souvik; Stinhauser, Amie L.; Traub, Linton M.; Madsen, Mette



Vitamin B12 deficiency in the brain leads to DNA hypomethylation in the TCblR/CD320 knockout mouse  

PubMed Central

Background DNA methylation is an epigenetic phenomenon that can modulate gene function by up or downregulation of gene expression. Vitamin B12 and folate pathways are involved in the production of S-Adenosylmethionine, the universal methyl donor. Findings Brain vitamin B12 concentration and global DNA methylation was determined in transcobalamin receptor (TCblR/CD320) knock out (KO) (n?=?4) and control mice (n?=?4) at 20–24?weeks of age. Median [IQR] brain vitamin B12 concentrations (pg/mg) in TCblR/CD320 KO mice compared with control mice was 8.59 [0.52] vs 112.42 [33.12]; p?vitamin B12 drops precipitously by as much as 90% during a 20?week period. This decrease is associated with a 40% decrease in global DNA methylation in the brain. Future research will reveal whether the disruption in gene expression profiles due to changes in DNA hypomethylation contribute to central nervous system pathologies that are frequently seen in vitamin B12 deficiency.



Low maternal vitamin B-12 status is associated with offspring insulin resistance regardless of antenatal micronutrient supplementation in rural Nepal.  


Questions have been raised about potentially negative effects of antenatal folic acid use in populations with a high prevalence of vitamin B-12 deficiency. Our objective was to examine the association between maternal folate and vitamin B-12 status in pregnancy on offspring insulin resistance and examine whether the effects of maternal micronutrient supplementation varied by baseline maternal folate and/or vitamin B-12 status. Pregnant women were cluster randomized to receive daily supplements containing vitamin A alone or with folic acid, folic acid+iron, folic acid+iron+zinc, or a multiple micronutrient. In a subsample (n = 1132), micronutrient status biomarkers were analyzed at baseline and late pregnancy. Children born to the women who participated in the trial were visited at 6-8 y of age. Fasting plasma glucose and insulin were used to estimate insulin resistance using the homeostasis model assessment (HOMA-IR). Children whose mothers were deficient in vitamin B-12 (<148 pmol/L, 27%) during early pregnancy had a 26.7% increase in HOMA-IR (P = 0.02), but there was no association with maternal folate status. Among children born to women who were vitamin B-12 deficient at baseline, the percent difference in HOMA-IR compared to the control group was 15.1% (95% CI: -35.9, 106.4), 4.9% (-41.6, 88.5), 3.3% (-38.4, 73.5), and 18.1% (-29.0, 96.7) in the folic acid, folic acid-iron, folic acid-iron-zinc, and multiple micronutrient supplementation groups, respectively, none of which were significant. Maternal vitamin B-12 deficiency is associated with an elevated risk of insulin resistance, but supplementation with folic acid or other micronutrients led to no significant change in insulin resistance in school-aged offspring. PMID:21865563

Stewart, Christine P; Christian, Parul; Schulze, Kerry J; Arguello, Margia; LeClerq, Steven C; Khatry, Subarna K; West, Keith P



Vitamin B12[c-lactone], a biologically inactive corrinoid compound, occurs in cultured and dried lion's mane mushroom (Hericium erinaceus) fruiting bodies.  


This study determined the vitamin B12 content of the edible medicinal mushroom Hericium erinaceus, lion's mane mushroom fruiting body, using a microbiological assay based on Lactobacillus delbrueckii ATCC 7830. Trace levels (0.04-0.36 ?g/100 g dry weight) of vitamin B12 were found in most of the dried mushroom samples, and two samples contained slightly higher levels (0.56 and 1.04 ?g/100 g dry weight, respectively) of vitamin B12. We purified the corrinoid compounds from the extracts of dried lion's mane mushroom fruiting bodies using an immunoaffinity column and identified them as vitamin B12 or vitamin B12[c-lactone] (or both) based on LC/ESI-MS/MS chromatograms. This is the first report on an unnatural corrinoid, vitamin B12[c-lactone], occurring in foods. Vitamin B12[c-lactone] was simple to produce during incubation of authentic vitamin B12 and chloramine-T, an antimicrobial agent, at varying pH values (3.0-7.0) and was completely inactive in the vitamin B12-dependent bacteria that are generally used in vitamin B12 bioassays. PMID:24506286

Teng, Fei; Bito, Tomohiro; Takenaka, Shigeo; Yabuta, Yukinori; Watanabe, Fumio



CdTe quantum dot as a fluorescence probe for vitamin B(12) in dosage form.  


We here report the CdTe quantum dot (CdTe QDs)-based sensor for probing vitamin B12 derivatives in aqueous solution. In this paper, simple and sensitive fluorescence quenching measurements has been employed. The Stern-Volmer constant (KSV), quenching rate constant (kq) and binding constant (K) were rationalized from fluorescence quenching measurement. Furthermore, the fluorescence resonance energy transfer (FRET) mechanism was discussed. This method was applicable over the concentration ranging from 1 to 14?g/mL (VB12) with correlation coefficient of 0.993. The limit of detection (LOD) of VB12 was found to be 0.15?g/mL. Moreover, the present approach opens a simple pathway for developing cost-effective, sensitive and selective QD-based fluorescence sensors/probes for biologically significant VB12 in pharmaceutical sample with mean recoveries in the range of 100-102.1%. PMID:23872019

Vaishnavi, E; Renganathan, R



Vitamin B12 Metabolism during Pregnancy and in Embryonic Mouse Models  

PubMed Central

Vitamin B12 (cobalamin, Cbl) is required for cellular metabolism. It is an essential coenzyme in mammals for two reactions: the conversion of homocysteine to methionine by the enzyme methionine synthase and the conversion of methylmalonyl-CoA to succinyl-CoA by the enzyme methylmalonyl-CoA mutase. Symptoms of Cbl deficiency are hematological, neurological and cognitive, including megaloblastic anaemia, tingling and numbness of the extremities, gait abnormalities, visual disturbances, memory loss and dementia. During pregnancy Cbl is essential, presumably because of its role in DNA synthesis and methionine synthesis; however, there are conflicting studies regarding an association between early pregnancy loss and Cbl deficiency. We here review the literature about the requirement for Cbl during pregnancy, and summarized what is known of the expression pattern and function of genes required for Cbl metabolism in embryonic mouse models.

Moreno-Garcia, Maira A.; Rosenblatt, David S.; Jerome-Majewska, Loydie A.



The cis influence of the corrin in vitamin B12 models  

NASA Astrophysics Data System (ADS)

Density Functional Theory (DFT) and Quantum Theory of Atoms in Molecules (QTAIM) calculations on [NH3[Co(III)(C10-X-corrin)]-CH3]+, where the C10-H of corrin is replaced by electron-donating or -withdrawing groups, X, explore the cis influence in these vitamin B12 models. As the electron donating ability of X increases, a normal trans influence is observed: the Co-NH3 bond weakens while the Co-CH3 bond strengthens. Surprisingly, though, the Co-CH3 bond dissociation energy decreases monotonically as the Co-C bond strengthens. This is found to be a consequence of the extent of shortening of the Co-NH3 during the homolysis reaction.

Govender, Penny P.; Navizet, Isabelle; Perry, Christopher B.; Marques, Helder M.



CdTe quantum dot as a fluorescence probe for vitamin B12 in dosage form  

NASA Astrophysics Data System (ADS)

We here report the CdTe quantum dot (CdTe QDs)-based sensor for probing vitamin B12 derivatives in aqueous solution. In this paper, simple and sensitive fluorescence quenching measurements has been employed. The Stern-Volmer constant (KSV), quenching rate constant (kq) and binding constant (K) were rationalized from fluorescence quenching measurement. Furthermore, the fluorescence resonance energy transfer (FRET) mechanism was discussed. This method was applicable over the concentration ranging from 1 to 14 ?g/mL (VB12) with correlation coefficient of 0.993. The limit of detection (LOD) of VB12 was found to be 0.15 ?g/mL. Moreover, the present approach opens a simple pathway for developing cost-effective, sensitive and selective QD-based fluorescence sensors/probes for biologically significant VB12 in pharmaceutical sample with mean recoveries in the range of 100-102.1%.

Vaishnavi, E.; Renganathan, R.



Apparent ruminal synthesis and intestinal disappearance of vitamin B12 and its analogs in dairy cows.  


The aim of the project was to calculate the apparent synthesis or destruction of cobalamin (vitamin B(12)) and its analogs in the rumen as well as their apparent intestinal disappearance in dairy cows. Four lactating cows were fed a diet supplemented with cobalt alone (0.76 mg/kg of DM; control) or with cobalt and vitamin B(12) (cyanocobalamin, 500 mg/d; treated). In addition to cobalamin, the only biologically active molecule for the cow, 7 analogs were identified in duodenal and ileal digesta: cobinamide, which lacks the base, ribose, and phosphate groups; and 6 other molecules in which the base, 5,6-dimethylbenzimidazole, is replaced by cresol, 2-CH(3)-adenine, adenine, 2-CH(3)-S-adenine, or 5-OH-benzimidazole, or an unidentified cobamine. Small amounts of cobalamin and cobinamide were detected in the total mixed ration, but apparent synthesis of all forms took place in rumen. During the control period, cobalamin represented 38% of the total amounts of corrinoids produced in rumen. Approximately 11% of the average daily intake of cobalt was used for apparent ruminal synthesis of corrinoids, of which only 4% was incorporated into cobalamin. Only 20% of the supplement of cyanocobalamin was recovered at the duodenal level; cobinamide appeared to be the major product of degradation of supplementary cyanocobalamin in the rumen. During the control and treatment periods, there was an apparent intestinal disappearance of cobalamin and 5-OH-benzimidazole cobamide only; only the apparent intestinal disappearance of cobalamin differed between the 2 periods. Although cobalamin was not the major form synthesized by ruminal microflora and, even if supplementary cyanocobalamin was extensively destroyed by ruminal microflora, based on calculations of apparent intestinal disappearance, cobalamin seems to be the major form absorbed in the small intestine. PMID:19700714

Girard, C L; Santschi, D E; Stabler, S P; Allen, R H



Biochemistry and clinical chemistry of vitamin B12 transport and the related diseases.  


This review focusses on research performed by the author and coworkers. The absorption, turnover and excretion of cobalamin and the pathogenesis of cobalamin deficiency states are described and the laboratory tests used to diagnose these states are discussed. Topics dealt with in detail include: overall turnover, daily need, enterohepatic circulation and excretion of cobalamin and other corrins . The soluble proteins mediating cobalamin transport and their cellular receptors are described and their nomenclature, isolation, structure and mode of action, the role of calcium in the membrane transport, the evolution of these systems and the analogies with transport systems for other substrates are discussed together with deficiency states, especially fish tapeworm anemia and familial selective vitamin B12 malabsorption with proteinuria. Folate deficiency is a relatively rare cause of megaloblastic anemia in Scandinavia but common in North America and explanations for this difference are suggested. The methods of assaying cobalamin in serum and plasma and the performance of radiovitamin B12 absorption tests are critically evaluated. The measurement of intrinsic factor in gastric juice, serum, amniotic fluid and urine is described. PMID:6329550

Gräsbeck, R



Nutritional Vitamin B12 Deficiency in a Breast-fed Infant of a Vegan-diet Mother  

Microsoft Academic Search

A 7-month-old male presented with lethargy and failure to thrive. The child was exclusively breast-fed from birth by a mother who was a strict vegetarian. Laboratory data revealed macrocytic anemia and methylmalonic acid in the urine, consistent with vitamin B12 deficient anemia. The patient responded well to supplementation with B12 alone and was developmentally normal by 11 months of age.

Ronald Sklar



Mutations in CUBN, encoding the intrinsic factor-vitamin B 12 receptor, cubilin, cause hereditary megaloblastic anaemia 1  

Microsoft Academic Search

Megaloblastic anaemia 1 (MGA1, OMIM 261100) is a rare, autosomal recessive disorder characterized by juvenile megaloblastic anaemia, as well as neurological symptoms that may be the only manifestations. At the cellular level, MGA1 is characterized by selective intestinal vitamin B12 (B12, cobalamin) malabsorption. MGA1 occurs worldwide, but its prevalence is higher in several Middle Eastern countries and Norway, and highest

Maria Aminoff; Jo Ellen Carter; Robert B. Chadwick; Cheryl Johnson; Ralph Gräsbeck; Mohamed A. Abdelaal; Harald Broch; Lasse B. Jenner; Pierre J. Verroust; Soeren K. Moestrup; Albert de la Chapelle; Ralf Krahe



A Case-Control Nutrigenomic Study on the Synergistic Activity of Folate and Vitamin B12 in Cervical Cancer Progression  

Microsoft Academic Search

The present study was designed to identify the role of folate, B12, homocysteine, and polymorphisms of methylene tetrahydrofolatereductase (MTHFR) gene in cervical carcinogenesis among 322 women from Kerala, South India. Serum folate, vitamin B12 (chemiluminescence assay), and homocysteine (EIA) along with genetic polymorphisms of MTHFR gene (polymerase chain reaction\\/restriction fragment length polymorphism) were analyzed for 136 control subjects, 92 low-grade

Preethi N. Ragasudha; Jissa V. Thulaseedharan; Ramani Wesley; P. G. Jayaprakash; Prema Lalitha; M. Radhakrishna Pillai



Overview of a roundtable on NHANES monitoring of biomarkers of folate and vitamin B-12 status: measurement procedure issues.  


A roundtable dialogue to discuss "NHANES Monitoring of Biomarkers of Folate and Vitamin B-12 Status" took place in July 2010. This article provides an overview of the meeting and this supplement issue. Although the focus of the roundtable dialogue was on the measurement of folate and vitamin B-12 status biomarkers in NHANES, this article also describes the relevance and importance of these issues for clinical and research laboratories. The roundtable identified the microbiological assay (MA) as the gold standard for measurement of serum and red blood cell folate concentrations. The roundtable noted that differences in results between the Bio-Rad Quantaphase II procedure (Bio-Rad Laboratories, Hercules, CA) that NHANES 1991-1994 and 1999-2006 used and the MA that NHANES 2007-2010 used will require adjustment equations to evaluate time trends. The roundtable found that the close agreement between the serum results for the MA and liquid chromatography-tandem mass spectrometry (LC-MS/MS) procedures supported the conversion to LC-MS/MS for serum folate in future NHANES. The roundtable recognized the uncertainty about whether subclinical vitamin B-12 deficiency is a public health concern but encouraged reinstatement of at least one circulating vitamin B-12 measure and one functional vitamin B-12 status measure in future NHANES. The use of serum vitamin B-12 and plasma methylmalonic acid would provide continuity with past NHANES. The roundtable supported the continued use of the National Institute of Standards and Technology (NIST) reference materials in NHANES biomarker analyses and the further development of additional reference materials by the NIST. PMID:21593504

Yetley, Elizabeth A; Coates, Paul M; Johnson, Clifford L



Overview of a roundtable on NHANES monitoring of biomarkers of folate and vitamin B-12 status: measurement procedure issues123456  

PubMed Central

A roundtable dialogue to discuss “NHANES Monitoring of Biomarkers of Folate and Vitamin B-12 Status” took place in July 2010. This article provides an overview of the meeting and this supplement issue. Although the focus of the roundtable dialogue was on the measurement of folate and vitamin B-12 status biomarkers in NHANES, this article also describes the relevance and importance of these issues for clinical and research laboratories. The roundtable identified the microbiological assay (MA) as the gold standard for measurement of serum and red blood cell folate concentrations. The roundtable noted that differences in results between the Bio-Rad Quantaphase II procedure (Bio-Rad Laboratories, Hercules, CA) that NHANES 1991–1994 and 1999–2006 used and the MA that NHANES 2007–2010 used will require adjustment equations to evaluate time trends. The roundtable found that the close agreement between the serum results for the MA and liquid chromatography–tandem mass spectrometry (LC-MS/MS) procedures supported the conversion to LC-MS/MS for serum folate in future NHANES. The roundtable recognized the uncertainty about whether subclinical vitamin B-12 deficiency is a public health concern but encouraged reinstatement of at least one circulating vitamin B-12 measure and one functional vitamin B-12 status measure in future NHANES. The use of serum vitamin B-12 and plasma methylmalonic acid would provide continuity with past NHANES. The roundtable supported the continued use of the National Institute of Standards and Technology (NIST) reference materials in NHANES biomarker analyses and the further development of additional reference materials by the NIST.

Johnson, Clifford L



Should vitamin B12 tablets be included in more Canadian drug formularies? An economic model of the cost-saving potential from increased utilisation of oral versus intramuscular vitamin B12 maintenance therapy for Alberta seniors  

PubMed Central

Objective The aim of this study was to estimate the cost-savings attainable if all patients aged ?65 years in Alberta, Canada, currently on intramuscular therapy were switched to oral therapy, from the perspective of a provincial ministry of health. Setting Primary care setting in Alberta, Canada. Participants Seniors of age 65 years and older currently receiving intramuscular vitamin B12 therapy. Intervention Oral vitamin B12 therapy at 1000??g/day versus intramuscular therapy at 1000??g/month. Primary and secondary outcome measures Cost saving from oral therapy over intramuscular therapy, from the perspective of the Alberta Ministry of Health, including drug costs, dispensing fees, injection administration fees, additional laboratory monitoring and physician visit fees. Results Over 5?years, if all Albertans aged 65 years and older who currently receive intramuscular B12 are switched to oral therapy, our model found that $C13?975?883 can be saved. Even if no additional physician visits are billed for among patients receiving intramuscular therapy, $C8?444?346 could be saved from reduced administration costs alone. Conclusions Oral B12 therapy has been shown to be an effective therapeutic option for patients with vitamin B12 deficiency, yet only three provinces and the Non-Insured Health Benefits program include oral tablets on their formulary rather than the parenteral preparation. To ensure judicious use of limited health resources, clinicians and formulary committees are encouraged to adopt oral B12 therapy as a clinically and cost-effective first-line therapy for vitamin B12 deficiency.

Houle, Sherilyn K D; Kolber, Michael R; Chuck, Anderson W



Investigation on the pH-dependent binding of vitamin B12 and lysozyme by fluorescence and absorbance  

NASA Astrophysics Data System (ADS)

The binding reaction between vitamin B12 (B12, cyanocobalamin) and lysozyme (Lys) has been investigated by fluorescence, synchronous fluorescence, ultraviolet-vis (UV) absorbance, and three-dimensional fluorescence. The intrinsic fluorescence of Lys was strongly quenched by the addition of B12 in different pH buffer solutions (pH 3.4, 7.4, and 9.0) and the spectroscopic observations are mainly rationalized in terms of a static quenching process at lower concentration of B12 ( CB12/ CLys < 5) and a combined quenching process at higher concentration of B12 ( CB12/ CLys > 5). The structural characteristics of B12 and Lys were probed, and their binding affinities were determined under different pH conditions (pH 3.4, 7.4, and 9.0). The effect of B12 on the conformation of Lys was analyzed using UV, synchronous fluorescence and three-dimensional fluorescence under different pH conditions. These results indicate that the binding of B12 to Lys causes apparent change in the secondary or tertiary structures of Lys. Furthermore, the effect of Zn 2+ on the binding constant of B12 with Lys under various pH conditions (pH 3.4, 7.4, and 9.0) was also studied.

Li, Daojin; Yang, Yumin; Cao, Xinxiang; Xu, Chen; Ji, Baoming



A randomized placebo-controlled crossover trial of aloe vera on bioavailability of vitamins C and B(12), blood glucose, and lipid profile in healthy human subjects.  


Several factors limit the absorption and bioavailability of vitamins. Vitamin C, a commonly used water-soluble supplement reduces the risk of disease. Vitamin B(12) is necessary for the development of RBC, growth, and nervous system. Vitamin B(12) deficiency is common among elderly. Thus, agents that improve bioavailability of vitamin C and B(12), especially in older individuals would be important. Aloe Vera is a botanical with immunomodulatory properties. Aloe is processed using the hand-filleted technique or whole leaf procedure. The aim of this study is to examine the effect of two different aloe vera preparations (aloe inner leaf gel, [AG] and aloe whole leaf decolorized gel, [AL]) compared to placebo on the bioavailability of vitamins, C and B(12), in healthy human volunteers in a randomized crossover trial. Subjects (n = 15) received in a random fashion either aloe whole leaf extract (AL with vitamins B(12), 1 mg and vitamin C 500 mg) or aloe fillet gel (AG with B(12) 1 mg and vitamin C 500 mg) or water (with vitamin B(12) 1 mg and vitamin C 500 mg). Blood was obtained fasting, followed by 1, 2, 4, 6, 8, and 24 hours postingestion of aloe/water. When given with vitamins C and B(12), AG significantly increased plasma oxygen radical absorbance capacity (ORAC) at both 4 and 24 hours and AL at 4 hours compared to baseline and placebo. AG significantly increased plasma vitamin C at 4, 6, 8, and 24 hours and AL at 4 and 6 hours compared to baseline and placebo (p <.01). Also, both aloes significantly increased serum vitamin B(12) levels at 1 and 2 hours compared to baseline and placebo (p <.01). Thus, AG and AL preparations are safe, well tolerated, and enhance the bioavailability of vitamins C and B(12) and antioxidant potential. PMID:22435613

Yun, Jung-Mi; Singh, Sital; Jialal, Rohan; Rockwood, Jason; Jialal, Ishwarlal; Devaraj, Sridevi



Vitamin B-12 and Folate Status in Relation to Decline in Scores on the Mini-Mental State Examination in the Framingham Heart Study  

PubMed Central

OBJECTIVES Biochemical evidence of low vitamin B-12 status is common in seniors, but its clinical relevance is unclear. Vitamin B-12 deficiency can result in rapid, irreversible cognitive decline – a phenomenon that has been linked to high folate status. Our objective was to investigate the cognitive significance of low to low-normal plasma vitamin B-12 concentrations. Secondarily, we sought to shed light on the role that folate status plays in the association between vitamin B-12 status and cognitive decline. DESIGN We evaluated associations between plasma vitamin B-12 and folate and 8-year cognitive decline. We also assessed interactions between vitamin B-12 status and both folate status and supplemental folate use in relation to cognitive decline. SETTING The Framingham Heart Study -- a prospective epidemiologic study PARTICIPANTS Five hundred forty-nine community-dwelling seniors (mean age 74.8±4.6 years). MEASUREMENTS Mini-Mental State Examination (MMSE), plasma folate, vitamin B-12, methylmalonic acid, homocysteine, demographic factors, and body mass index. RESULTS MMSE scores declined by 0.24 points/year over the 8-year follow-up period. Decline was significantly accelerated among cohort members in the bottom two plasma vitamin B-12 quintile categories, and no apparent cognitive advantage was associated with plasma vitamin B-12 from 187–256.8 pmol/L versus <186 pmol/L. Among cohort members with plasma vitamin B-12<258 pmol/L, having a plasma folate concentration>20.2 nmol/L was associated with an approximate 1-point/year decline, as was use of supplemental folate. CONCLUSION Plasma vitamin B-12 from 187–256.8 pmol/L predicts cognitive decline. High plasma folate and supplemental folate use identify subgroups in this vitamin B-12 range and below who are prone to especially rapid cognitive decline.

Morris, Martha Savaria; Selhub, Jacob; Jacques, Paul F.



Mood disorder with mixed, psychotic features due to vitamin b12 deficiency in an adolescent: case report  

PubMed Central

Vitamin B12 is one of the essential vitamins affecting various systems of the body. Reports of psychiatric disorders due to its deficiency mostly focus on middle aged and elderly patients. Here we report a case of vitamin B 12 deficiency in a 16-year old, male adolescent who presented with mixed mood disorder symptoms with psychotic features. Chief complaints were “irritability, regressive behavior, apathy, crying and truancy” which lasted for a year. Premorbid personality was unremarkable with no substance use/exposure or infections. No stressors were present. The patient was not vegetarian. Past medical history and family history was normal. Neurological examination revealed glossitis, ataxia, rigidity in both shoulders, cog-wheel rigidity in the left elbow, bilateral problems of coordination in cerebellar examination, reduced swinging of the arms and masked face. Romberg’s sign was present. Laboratory evaluations were normal. Endoscopy and biopsy revealed atrophy of the gastric mucosa with Helicobacter Pylori colonization. Schilling test was suggestive of malabsorbtion. He was diagnosed with Mood disorder with Mixed, Psychotic Features due to Vitamin B12 Deficiency and risperidone 0.5?mg/day and intramuscular vitamin B12 500 mcg/day were started along with referral for treatment of Helicobacter pylori. A visit on the second week revealed no psychotic features. Romberg’s sign was negative and cerebellar tests were normal. Extrapyramidal symptoms were reduced while Vitamin B12 levels were elevated. Risperidone was stopped and parenteral Vitamin B12 treatment was continued with monthly injections for 3?months. Follow-up endoscopy and biopsy at the first month demonstrated eradication of H. pylori. He was followed monthly for another 6?months and psychiatric symptoms did not recur at the time of last evaluation. Despite limitations, this case may underline the observation that mood disorders with psychotic features especially with accompanying extrapyramidal symptoms lacking a clear etiology may be rare manifestation of vitamin B12 and/or folate deficiency in children and adolescents and be potentially amenable to treatment.



Effects of Dietary Supplements of Folic Acid and Vitamin B12 on Metabolism of Dairy Cows in Early Lactation1  

Microsoft Academic Search

The present experiment was undertaken to deter- mine the effects of dietary supplements of folic acid and vitamin B12 given from 3 wk before to 8 wk after calving on lactational performance and metabolism of 24 mul- tiparous Holstein cows assigned to 6 blocks of 4 cows each according to their previous milk production. Sup- plementary folic acid at 0

B. Graulet; J. J. Matte; A. Desrochers; L. Doepel; M.-F. Palin; C. L. Girard



Vitamin B12, Folate, Homocysteine, and Bone Health in Adults and Elderly People: A Systematic Review with Meta-Analyses  

PubMed Central

Elevated homocysteine levels and low vitamin B12 and folate levels have been associated with deteriorated bone health. This systematic literature review with dose-response meta-analyses summarizes the available scientific evidence on associations of vitamin B12, folate, and homocysteine status with fractures and bone mineral density (BMD). Twenty-seven eligible cross-sectional (n = 14) and prospective (n = 13) observational studies and one RCT were identified. Meta-analysis on four prospective studies including 7475 people showed a modest decrease in fracture risk of 4% per 50?pmol/L increase in vitamin B12 levels, which was borderline significant (RR = 0.96, 95% CI = 0.92 to 1.00). Meta-analysis of eight studies including 11511 people showed an increased fracture risk of 4% per ?mol/L increase in homocysteine concentration (RR = 1.04, 95% CI = 1.02 to 1.07). We could not draw a conclusion regarding folate levels and fracture risk, as too few studies investigated this association. Meta-analyses regarding vitamin B12, folate and homocysteine levels, and BMD were possible in female populations only and showed no associations. Results from studies regarding BMD that could not be included in the meta-analyses were not univocal.

van Wijngaarden, J. P.; Doets, E. L.; Szczecinska, A.; Souverein, O. W.; Duffy, M. E.; Dullemeijer, C.; Cavelaars, A. E. J. M.; Pietruszka, B.; van't Veer, P.; Brzozowska, A.; Dhonukshe-Rutten, R. A. M.; de Groot, C. P. G. M.



Vitamin B12, folate, homocysteine, and bone health in adults and elderly people: a systematic review with meta-analyses.  


Elevated homocysteine levels and low vitamin B12 and folate levels have been associated with deteriorated bone health. This systematic literature review with dose-response meta-analyses summarizes the available scientific evidence on associations of vitamin B12, folate, and homocysteine status with fractures and bone mineral density (BMD). Twenty-seven eligible cross-sectional (n = 14) and prospective (n = 13) observational studies and one RCT were identified. Meta-analysis on four prospective studies including 7475 people showed a modest decrease in fracture risk of 4% per 50?pmol/L increase in vitamin B12 levels, which was borderline significant (RR = 0.96, 95% CI = 0.92 to 1.00). Meta-analysis of eight studies including 11511 people showed an increased fracture risk of 4% per ? mol/L increase in homocysteine concentration (RR = 1.04, 95% CI = 1.02 to 1.07). We could not draw a conclusion regarding folate levels and fracture risk, as too few studies investigated this association. Meta-analyses regarding vitamin B12, folate and homocysteine levels, and BMD were possible in female populations only and showed no associations. Results from studies regarding BMD that could not be included in the meta-analyses were not univocal. PMID:23509616

van Wijngaarden, J P; Doets, E L; Szczeci?ska, A; Souverein, O W; Duffy, M E; Dullemeijer, C; Cavelaars, A E J M; Pietruszka, B; Van't Veer, P; Brzozowska, A; Dhonukshe-Rutten, R A M; de Groot, C P G M



Transcobalamin C776G Genotype Modifies the Association between Vitamin B12 and Homocysteine in Older Hispanics  

PubMed Central

Background A common polymorphism, C776G, in the plasma B12 transport protein transcobalamin (TC), encodes for either proline or arginine at codon 259. This polymorphism may affect the affinity of TC for B12 and subsequent delivery of B12 to tissues. Methods TC genotype and its associations with indicators of B12 status, including total B12, holotranscobalamin (holoTC), methylmalonic acid, and homocysteine, were evaluated in a cohort of elderly Latinos (N=554, age 60–93y) from the Sacramento Area Latino Study on Aging (SALSA). Results The distribution of TC genotypes was 41.3% homozygous reference (776CC) and 11.6% homozygous variant (776GG). No differences between the homozygous genotypes were observed in total B12, holoTC, methylmalonic acid, or homocysteine. The holoTC/total B12 ratio was lower in the 776GG group compared with the 776CC group (p=0.04). Significant interactions of TC genotype with total B12 (p=0.04) and with holoTC (p?0.03) were observed such that mean homocysteine concentrations and the odds ratios for hyperhomocysteinemia (>13 µmol/L) were higher in the 776CC subjects compared with all carriers of the G allele (776CG and 776GG combined) when total B12 (<156 pmol/L) or holoTC (<35 pmol/L) were low. Conclusions This population of older Latinos has a lower prevalence of the TC 776GG variant than reported for Caucasian populations. The association between vitamin B12 and homocysteine concentrations is modified by TC 776 genotype. It remains to be determined if the TC C776G polymorphism has a significant effect on the hematological and neurological manifestations of B12 deficiency or on vascular and other morbidities associated with hyperhomocysteinemia.

Garrod, Marjorie G.; Allen, Lindsay H.; Haan, Mary N.; Green, Ralph; Miller, Joshua W.



Nucleotide sequence of the gene for the vitamin B12 receptor protein in the outer membrane of Escherichia coli.  

PubMed Central

The nucleotide sequence of a 2220-base-pair fragment containing the btuB gene of Escherichia coli was determined. There was a single open reading frame which was translated into a 614-amino-acid polypeptide, the first 20 amino acids of which comprised a typical leader sequence. The putative mature or processed form had a molecular weight (66,400) and a composition in close agreement with that determined for the purified receptor. The distribution of amino acids in the receptor protein was similar to that of other outer membrane proteins, showing a fairly even distribution of charged residues and the absence of extensive hydrophobic stretches. The btuB451 mutation appears to alter the receptor to eliminate its ability to function in vitamin B12 uptake without affecting its ligand binding properties. The sequence of the DNA from this mutant was determined and revealed a leucine-to-proline (C-to-T transition) change in the eighth amino acid of the mature form. Images

Heller, K; Kadner, R J



Substitution of Co alpha-(5-hydroxybenzimidazolyl)cobamide (factor III) by vitamin B12 in Methanobacterium thermoautotrophicum.  

PubMed Central

Methanobacterium thermoautotrophicum grown on mineral medium contains 120 nmol of Co alpha-(5-hydroxybenzimidazolyl)cobamides (derivatives of factor III) per g of dry cell mass as the sole cobamide. The bacterium assimilated several corrinoids and benzimidazole bases during autotrophic growth. The corrinoids were converted into factor III; however, after three transfers in 5,6-dimethylbenzimidazole (200 microM)-supplemented mineral medium, derivatives of factor III were completely replaced by derivatives of vitamin B12, which is atypical for methanogens. The total cobamide content of these cells and their growth rate were not affected compared with factor III-containing cells. Therefore, the high cobamide content rather than a particular type of cobamide is required for metabolism of methanogens. Derivatives of factor III are not essential cofactors of cobamide-containing enzymes from methanogenic bacteria, but they are the result of a unique biosynthetic ability of these archaebacteria. The cobamide biosynthesis include unspecific enzymes, which made it possible either to convert non-species-derived corrinoids into derivatives of factor III or to synthesize other types of cobamides than factor III. The cobamide biosynthesis is regulated by its end product. In addition, the uptake of extracellular cobamides is controlled, and the assimilated corrinoids regulate cellular cobamide biosynthesis.

Stupperich, E; Steiner, I; Eisinger, H J



Abdominal aortic aneurysm and the association with serum levels of Homocysteine, vitamins B6, B12 and Folate  

PubMed Central

Previous investigations have shown hyperhomocysteinemi in patients with abdominal aortic aneurysm (AAA). In the present study we evaluated the circulating level of homocysteine (Hcy) in relation to renal function, vitamins B6, B12 and folate status in AAA patients with special regard to aneurysm size, and rupture. Hcy, Creatinine, B6, B12 and folate were measured in 119 patients with AAA and 36 controls without aneurysm matched by age, gender and smoking habit. As expected there was a weak correlation between Hcy and vitamins B6, B12 or folate. We found similar levels of Hcy, B6 and folic acid in patients with nonruptured AAA compared to the control group matched by age, gender and smoking habit. There was no correlation between maximum diameter of the nonruptured AAA (n=78) and Hcy, B6 or folate. However, the present study shows a significant inverse correlation between maximum diameter of the nonruptured AAA (n=78) and B12 (r = -0.304, p=0.007) with significant higher levels in small AAA compared to large AAA. In conclusion, Hcy does not seem to be a useful biomarker in AAA disease. The unexpected finding of B12 levels correlating to aneurysm diameter warrants urgent further investigation of B12 supplement to prevent progression of small AAA.

Lindqvist, Markus; Hellstrom, Anders; Henriksson, Anders E



Effects of supplementary folic acid and vitamin B(12) on hepatic metabolism of dairy cows according to methionine supply.  


The present experiment was undertaken to study the interactions between dietary supplements of rumen-protected methionine (RPM) and intramuscular injections of folic acid and vitamin B(12), given from 3 wk before calving to 16 wk of lactation, on hepatic metabolism of lactating dairy cows. Sixty multiparous Holstein cows were assigned to 10 blocks of 6 cows each according to their previous milk production. Within each block, 3 cows were fed a diet calculated to supply Met as 1.83% of metabolizable protein, whereas the 3 other cows were fed the same diet supplemented with 18g of RPM calculated to provide Met as 2.23% of metabolizable protein. Within each level of Met, the cows received no vitamin supplement or weekly intramuscular injections of 160mg of folic acid alone or combined with 10mg of vitamin B(12). Liver biopsies were taken at 2, 4, 8, and 16 wk of lactation. Liver concentrations of folates and vitamin B(12) were increased by their respective supplements but this response to vitamin supplements was altered by methionine supply. Concentrations of total lipids and triglycerides increased in livers of cows fed RPM, whereas concentrations of cholesterol ester, cholesterol, diglycerides, phosphatidylethanolamine, and phosphatidylcholine were not affected. Folic acid, alone or combined with vitamin B(12), tended to increase the ratio of phosphatidylcholine to phosphatidylethanolamine. Gene expression of 5,10-methylene-tetrahydrofolate reductase, microsomal transfer protein, and phosphatidylethanolamine methyltransferase were higher in liver of cows fed RPM supplements. The relative mRNA abundance of 5,10-methylene-tetrahydrofolate reductase and methylmalonyl-CoA mutase were increased by the combined injections of folic acid and vitamin B(12), whereas those of methionine synthase and methionine synthase reductase were not affected by treatments. These results suggest that increasing supply of methyl groups, as preformed labile methyl groups or through methylneogenesis, affected the methylation cycle but had a limited effect on dairy cow performance. The observed effects of the combined supplement of folic acid and vitamin B(12) on lactational performance of dairy cows probably result from an improvement of energy metabolism during early lactation. PMID:20412928

Preynat, A; Lapierre, H; Thivierge, M C; Palin, M F; Cardinault, N; Matte, J J; Desrochers, A; Girard, C L



Vitamin B12-Mediated Restoration of Defective Anaerobic Growth Leads to Reduced Biofilm Formation in Pseudomonas aeruginosa  

PubMed Central

Pseudomonas aeruginosa undergoes cell elongation and forms robust biofilms during anaerobic respiratory growth using nitrate (NO3?) as an alternative electron acceptor. Understanding the mechanism of cell shape change induced upon anaerobiosis is crucial to the development of effective treatments against P. aeruginosa biofilm infection. Here, we uncovered the molecular basis of anaerobiosis-triggered cell elongation and identified vitamin B12 to be a molecule that can reinstate defective anaerobic growth of P. aeruginosa. The ratio of total cellular DNA content to protein content was significantly decreased in the PAO1 strain grown under anaerobic conditions, indicating that DNA replication is impaired during anaerobic growth. Anaerobic growth of PAO1 reached a higher cell density in the presence of vitamin B12, an essential coenzyme of class II ribonucleotide reductase. In addition, cell morphology returned to a normal rod shape and transcription of stress-response genes was downregulated under the same anaerobic growth conditions. These results suggest that vitamin B12, the production of which was suppressed during anaerobic growth, can restore cellular machineries for DNA replication and therefore facilitate better anaerobic growth of P. aeruginosa with normal cell division. Importantly, biofilm formation was substantially decreased when grown with vitamin B12, further demonstrating that anaerobiosis-induced cell elongation is responsible for robust biofilm formation. Taken together, our data reveal mechanistic details of a morphological change that naturally occurs during anaerobic growth of P. aeruginosa and illustrates the ability of vitamin B12 to modulate the biofilm-forming capacity of P. aeruginosa under such condition.

Lee, Kang-Mu; Go, Junhyeok; Yoon, Mi Young; Park, Yongjin; Kim, Sang Cheol; Yong, Dong Eun



Cervical spondylotic myelopathy with vitamin B12 deficiency: Two case reports  

PubMed Central

Although it has been observed that a vitamin B12 (VB12) deficiency may lead to defects in the nervous system, there is a lack of studies elucidating whether VB12 has a role in the pathogenesis of cervical spondylotic myelopathy (CSM). The present study describes two cases of CSM observed in the clinic, where the patients presented with common characteristics of the typical clinical symptoms; however, T2-weighted magnetic resonance imaging examinations revealed that although the degree of spinal cord compression was not serious, the spinal cord exhibited significant high signal changes. At the same time, the serum VB12 levels of the two patients were lower compared with those of normal controls. The symptoms of the patients improved following anterior cervical decompression surgery and VB12 replacement therapy. The incidence of CSM in the two patients may have been correlated with a lack of VB12. Therefore, it is recommended that the serum VB12 levels are checked in cases of CSM where the standard imaging and clinical manifestations do not fully match.




Stimulation in vitro of vitamin B12-dependent methionine synthase by polyamines.  


Vitamin B12-dependent methionine synthase is an important enzyme for sulphur amino acid, folate polyamine metabolism, S-adenosylmethionine metabolism and also in the methylation pathway of DNA, RNA, proteins and lipids. Consequently, studies aiming at exploring the control and regulation of methionine synthase are of particular interest. Here we report the modulation of enzyme activity in vitro by polyamines. Although putrescine, cadaverine, spermine and spermidine all stimulated enzyme activity, the last two were the most potent, causing increases in enzyme activity up to 400%. The EC50 for spermine was determined as 8 microM and for spermidine 40 microM. The physiological concentration for spermine has been reported to be 15-19 microM. Spermine was found to increase both the Km and the V(max) with respect to methyltetrahydrofolate for the enzyme. These data support the hypothesis that spermine and spermidine are feedback regulators of methionine synthase both in vivo and in vitro and are consistent with the polyamines' regulating cell signalling pathways. PMID:8687414

Kenyon, S H; Nicolaou, A; Ast, T; Gibbons, W A



Subacute combined degeneration of the spinal cord despite prophylactic vitamin B12 treatment.  


We describe a 35 year-old man presenting with a four-week history of non-painful limb paraesthesias and unsteady gait causing falls. On examination he had an ataxic gait associated with dorsal column sensory loss. He had a medical history of a partial gastrectomy six years prior and anaemia. He had received monthly intramuscular hydroxycobalamin injections since the gastrectomy. Laboratory tests revealed normal vitamin B12 and holotranscobalamin levels, a reduced serum caeruloplasmin of 0.05 g/L (normal: 0.22-0.58 g/L), a copper-to-caeruloplasmin ratio of 1.9 ?mol/L (11.0-22.0 ?mol/L) and a reduced 24-hour urinary copper concentration of <0.30 ?mol/L (0-0.3 ?mol/L). Cerebrospinal fluid analysis, nerve conduction studies, electromyography and visual-evoked responses were unremarkable. MRI revealed abnormal hyperintense signal in the cervical dorsal columns. Hypocupric myelopathy was diagnosed and he was treated with daily oral elemental copper. Three months later, his walking and balance had improved although there was no change noted on MRI. PMID:22342235

Tsang, Benjamin K-T; Crump, Nicholas; Macdonell, Richard A



Stimulation in vitro of vitamin B12-dependent methionine synthase by polyamines.  

PubMed Central

Vitamin B12-dependent methionine synthase is an important enzyme for sulphur amino acid, folate polyamine metabolism, S-adenosylmethionine metabolism and also in the methylation pathway of DNA, RNA, proteins and lipids. Consequently, studies aiming at exploring the control and regulation of methionine synthase are of particular interest. Here we report the modulation of enzyme activity in vitro by polyamines. Although putrescine, cadaverine, spermine and spermidine all stimulated enzyme activity, the last two were the most potent, causing increases in enzyme activity up to 400%. The EC50 for spermine was determined as 8 microM and for spermidine 40 microM. The physiological concentration for spermine has been reported to be 15-19 microM. Spermine was found to increase both the Km and the V(max) with respect to methyltetrahydrofolate for the enzyme. These data support the hypothesis that spermine and spermidine are feedback regulators of methionine synthase both in vivo and in vitro and are consistent with the polyamines' regulating cell signalling pathways.

Kenyon, S H; Nicolaou, A; Ast, T; Gibbons, W A



Elevated Vitamin B12 Levels in Autoimmune Lymphoproliferative Syndrome Attributable to Elevated Haptocorrin in Lymphocytes  

PubMed Central

Objective Identify the etiology of elevated B12 in autoimmune lymphoproliferative syndrome (ALPS). Design Peripheral blood of ALPS patients with elevated B12 and controls were evaluated. Results Total and holo-haptocorrin (HC) levels were 26- and 23-fold higher in ALPS patients, respectively. No abnormal B12-binding proteins were found. Western blot revealed HC in lymphocyte lysates only from ALPS patients. Conclusion Elevated concentrations of B12 found in ALPS patients were due to increased lymphocyte expression of HC.

Bowen, Raffick A.R.; Dowdell, Kennichi C.; Dale, Janet K.; Drake, Steven K.; Fleisher, Thomas A.; Hortin, Glen L.; Remaley, Alan T.; Nexo, Ebba; Rao, V. Koneti



Effect of pH on the interaction of vitamin B12 with bovine serum albumin by spectroscopic approaches  

NASA Astrophysics Data System (ADS)

The interaction mechanism between vitamin B12 (B12, cyanocobalamin) and bovine serum albumin (BSA) has been investigated by fluorescence, synchronous fluorescence, ultraviolet-vis (UV) absorbance, and three-dimensional fluorescence. The intrinsic fluorescence of BSA was strongly quenched by the addition of B12 in different pH buffer solutions (pH 2.5, 3.5, 5.0, 7.4, and 9.0) and spectroscopic observations are mainly rationalized in terms of a static quenching process at lower concentration of B12 ( CB12/ CBSA < 5) and a combined quenching process at higher concentration of B12 ( CB12/ CBSA > 5). The structural characteristics of B12 and BSA were probed, and their binding affinities were determined under different pH conditions. The results indicated that the binding abilities of B12 to BSA in the acidic and basic pH regions (pH 2.5, 3.5, 5.0, and 9.0) were lower than that at simulating physiological condition (pH 7.4). In addition, the efficiency of energy transfer from tryptophan fluorescence to B12 was found to depend on the binding distance r between the donor and acceptor calculated using Förster's theory. The effect of B12 on the conformation of BSA was analyzed using UV, synchronous fluorescence and three-dimensional fluorescence under different pH conditions. These results showed that the binding of B12 to BSA causes apparent change in the secondary and tertiary structures of BSA.

Li, Daojin; Zhang, Tian; Xu, Chen; Ji, Baoming



Folate, Vitamin B12 and Homocysteine Status in Women of Childbearing Age: Baseline Data of Folic Acid Wheat Flour Fortification in Iran  

Microsoft Academic Search

Background: Folic acid fortification implemented mandatorily in many countries has been associated with significant increase in blood folate concentrations and reduction in the prevalence of neural tube defects. However, there are controversial findings on the probability of vitamin B12 deficiency being masked in the population after folic acid fortification. Baseline data on folate and vitamin B12 status are necessary before

Z. Abdollahi; I. Elmadfa; A. Djazayeri; S. Sadeghian; H. Freisling; F. Salehi Mazandarani; K. Mohamed



Relation of folates, vitamin B12 and homocysteine to vertebral bone mineral density change in postmenopausal women. A five-year longitudinal evaluation  

Microsoft Academic Search

Elevation of homocysteine is associated with an increased risk for bone fractures. Whether the risk is due to homocysteine or to the reduced levels of cofactors necessary for its metabolisation, such as folates or vitamin B12, is not completely clear. In this study we wanted to determine whether in postmenopausal women, levels of folates, homocysteine or vitamin B12 are predictive

Angelo Cagnacci; Bruno Bagni; Annalisa Zini; Marianna Cannoletta; Matteo Generali; Annibale Volpe



Sub-Optimal Vitamin B-12 Levels among ART-Na?ve HIV-Positive Individuals in an Urban Cohort in Uganda  

PubMed Central

Malnutrition is common among HIV-infected individuals and is often accompanied by low serum levels of micronutrients. Vitamin B-12 deficiency has been associated with various factors including faster HIV disease progression and CD4 depletion in resource-rich settings. To describe prevalence and factors associated with sub-optimal vitamin B-12 levels among HIV-infected antiretroviral therapy (ART) naïve adults in a resource-poor setting, we performed a cross-sectional study with a retrospective chart review among individuals attending either the Mulago-Mbarara teaching hospitals’ Joint AIDS Program (MJAP) or the Infectious Diseases Institute (IDI) clinics, in Kampala, Uganda. Logistic regression was used to determine factors associated with sub-optimal vitamin B-12. The mean vitamin B-12 level was 384 pg/ml, normal range (200–900). Sub-optimal vitamin B-12 levels (<300 pg/ml) were found in 75/204 (36.8%). Twenty-one of 204 (10.3%) had vitamin B-12 deficiency (<200 pg/ml) while 54/204 (26.5%) had marginal depletion (200–300 pg/ml). Irritable mood was observed more among individuals with sub-optimal vitamin B-12 levels (OR 2.5, 95% CI; 1.1–5.6, P?=?0.03). Increasing MCV was associated with decreasing serum B-12 category; 86.9 fl (±5.1) vs. 83 fl (±8.4) vs. 82 fl (±8.4) for B-12 deficiency, marginal and normal B-12 categories respectively (test for trend, P?=?0.017). Compared to normal B-12, individuals with vitamin B-12 deficiency had a longer known duration of HIV infection: 42.2 months (±27.1) vs. 29.4 months (±23.8; P?=?0.02). Participants eligible for ART (CD4<350 cells/µl) with sub-optimal B-12 had a higher mean rate of CD4 decline compared to counterparts with normal B-12; 118 (±145) vs. 22 (±115) cells/µl/year, P?=?0.01 respectively. The prevalence of a sub-optimal vitamin B-12 was high in this HIV-infected, ART-naïve adult clinic population in urban Uganda. We recommend prospective studies to further clarify the causal relationships of sub-optimal vitamin B-12, and explore the role of vitamin B-12 supplementation in immune recovery.

Semeere, Aggrey S.; Nakanjako, Damalie; Ddungu, Henry; Kambugu, Andrew; Manabe, Yukari C.; Colebunders, Robert



Combined spectroscopic/computational studies of vitamin B12 precursors: geometric and electronic structures of cobinamides.  


Vitamin B(12) (cyanocobalamin) and its biologically active derivatives, methylcobalamin and adenosylcobalamin, are members of the family of corrinoids, which also includes cobinamides. As biological precursors to cobalamins, cobinamides possess the same structural core, consisting of a low-spin Co(3+) ion that is ligated equatorially by the four nitrogens of a highly substituted tetrapyrrole macrocycle (the corrin ring), but differ with respect to the lower axial ligation. Specifically, cobinamides possess a water molecule instead of the nucleotide loop that coordinates axially to Co(3+)cobalamins via its dimethylbenzimidazole (DMB) base. Compared to the cobalamin species, cobinamides have proven much more difficult to study experimentally, thus far eluding characterization by X-ray crystallography. In this study, we have utilized combined quantum mechanics/molecular mechanics (QM/MM) computations to generate complete structural models of a representative set of cobinamide species with varying upper axial ligands. To validate the use of this approach, analogous QM/MM geometry optimizations were carried out on entire models of the cobalamin counterparts for which high-resolution X-ray structural data are available. The accuracy of the cobinamide structures was assessed further by comparing electronic absorption spectra computed using time-dependent density functional theory to those obtained experimentally. Collectively, the results obtained in this study indicate that the DMB ? H(2)O lower axial ligand switch primarily affects the energies of the Co 3d(z(2))-based molecular orbital (MO) and, to a lesser extent, the other Co 3d-based MOs as well as the corrin ?-based highest energy MO. Thus, while the energy of the lowest-energy electronic transition of cobalamins changes considerably as a function of the upper axial ligand, it is nearly invariant for the cobinamides. PMID:22332807

Reig, Amanda J; Conrad, Karen S; Brunold, Thomas C



Electronic and structural properties of low-lying excited states of vitamin B12.  


Time-dependent density functional theory (TD-DFT) has been applied to explore electronically excited states of vitamin B(12) (cyanocobalamin or CNCbl). To explain why the Co-C bond in CNCbl does not undergo photodissociation under conditions of simple photon excitation, electronically excited states have been computed along the Co-C(CN) stretched coordinate. It was found that the repulsive (3)(?(Co-C) ? ?*(Co-C)) triplet state drops in energy as the Co-C(CN) bond lengthens, but it does not become dissociative. Low-lying excited states were also computed as function of two axial bond lengths. Two energy minima have been located on the S(1)/CNCbl, as well as T(1)/CNCbl, surfaces. The full geometry optimization was carried out for each minimum and electronic properties associated with each optimized structure were analyzed in details. One minimum was described as excitation having mixed ??*/MLCT (metal-to-ligand charge transfer) character, while the second as ligand-to-metal charge transfer (LMCT) transition. Neither of them, however, can be viewed as pure MLCT or LMCT transitions since additional excitation to or from ?-bonds (SB) of N-Co-C unit have also noticeable contributions. Inclusion of solvent altered the character of one of the excitations from ??*/MLCT/SBLCT to ??*/LMCT/LSBCT-type, and therefore, both of them gained significant contribution from LMCT/LSBCT transition. Finally, the nature of S(1) electronic state has been comparatively analyzed in CNCbl and MeCbl cobalamins. PMID:21894986

Lodowski, Piotr; Jaworska, Maria; Kornobis, Karina; Andruniów, Tadeusz; Kozlowski, Pawel M



Elucidation of the anaerobic pathway for the corrin component of cobalamin (vitamin B12).  


It has been known for the past 20 years that two pathways exist in nature for the de novo biosynthesis of the coenzyme form of vitamin B12, adenosylcobalamin, representing aerobic and anaerobic routes. In contrast to the aerobic pathway, the anaerobic route has remained enigmatic because many of its intermediates have proven technically challenging to isolate, because of their inherent instability. However, by studying the anaerobic cobalamin biosynthetic pathway in Bacillus megaterium and using homologously overproduced enzymes, it has been possible to isolate all of the intermediates between uroporphyrinogen III and cobyrinic acid. Consequently, it has been possible to detail the activities of purified cobinamide biosynthesis (Cbi) proteins CbiF, CbiG, CbiD, CbiJ, CbiET, and CbiC, as well as show the direct in vitro conversion of 5-aminolevulinic acid into cobyrinic acid using a mixture of 14 purified enzymes. This approach has resulted in the isolation of the long sought intermediates, cobalt-precorrin-6A and -6B and cobalt-precorrin-8. EPR, in particular, has proven an effective technique in following these transformations with the cobalt(II) paramagnetic electron in the dyz orbital, rather than the typical dz2. This result has allowed us to speculate that the metal ion plays an unexpected role in assisting the interconversion of pathway intermediates. By determining a function for all of the pathway enzymes, we complete the tool set for cobalamin biosynthesis and pave the way for not only enhancing cobalamin production, but also design of cobalamin derivatives through their combinatorial use and modification. PMID:23922391

Moore, Simon J; Lawrence, Andrew D; Biedendieck, Rebekka; Deery, Evelyne; Frank, Stefanie; Howard, Mark J; Rigby, Stephen E J; Warren, Martin J



Role of vitamin B12 on methylmalonyl-CoA mutase activity*  

PubMed Central

Vitamin B12 is an organometallic compound with important metabolic derivatives that act as cofactors of certain enzymes, which have been grouped into three subfamilies depending on their cofactors. Among them, methylmalonyl-CoA mutase (MCM) has been extensively studied. This enzyme catalyzes the reversible isomerization of L-methylmalonyl-CoA to succinyl-CoA using adenosylcobalamin (AdoCbl) as a cofactor participating in the generation of radicals that allow isomerization of the substrate. The crystal structure of MCM determined in Propionibacterium freudenreichii var. shermanii has helped to elucidate the role of this cofactor AdoCbl in the reaction to specify the mechanism by which radicals are generated from the coenzyme and to clarify the interactions between the enzyme, coenzyme, and substrate. The existence of human methylmalonic acidemia (MMA) due to the presence of mutations in MCM shows the importance of its role in metabolism. The recent crystallization of the human MCM has shown that despite being similar to the bacterial protein, there are significant differences in the structural organization of the two proteins. Recent studies have identified the involvement of an accessory protein called MMAA, which interacts with MCM to prevent MCM’s inactivation or acts as a chaperone to promote regeneration of inactivated enzyme. The interdisciplinary studies using this protein as a model in different organisms have helped to elucidate the mechanism of action of this isomerase, the impact of mutations at a functional level and their repercussion in the development and progression of MMA in humans. It is still necessary to study the mechanisms involved in more detail using new methods.

Takahashi-Iniguez, Toshiko; Garcia-Hernandez, Enrique; Arreguin-Espinosa, Roberto; Flores, Maria Elena



A puzzle of hemolytic anemia, iron and vitamin B12 deficiencies in a 52-year-old male.  


A 52-year-old male with no significant past medical history reports increasing generalized fatigue and weakness for the past 2 weeks. Physical examination reveals jaundice and pallor without organomegaly or lymphadenopathy. His hemoglobin was 5.9?g/dL with a mean corpuscular volume of 87.1?fL and elevated red blood cell distribution width of 30.7%. His liver function test was normal except for elevated total bilirubin of 3.7?mg/dL. Serum LDH was 701?IU/L, and serum haptoglobin was undetectable. Further investigation revealed serum vitamin B12 of <30?pg/mL with elevated methylmalonic acid and homocysteine level. In addition, serum ferritin and transferrin saturation were low. The patient was diagnosed with hemolytic anemia secondary to vitamin B12 deficiency with concomitant iron deficiency anemia. PMID:24083040

Prueksaritanond, Suartcha; Barbaryan, Aram; Mirrakhimov, Aibek E; Liana, Palacci; Ali, Alaa M; Gilman, Alan D



Elevated Serum Vitamin B12 Levels in Association With Tumor Markers as the Prognostic Factors Predictive for Poor Survival in Patients With Hepatocellular Carcinoma  

Microsoft Academic Search

Elevated blood vitamin B12 (VitB12) level has recently been identified as a prognostic indicator for advanced cancer patients. The predictive value of blood VitB12 for survival of patients with hepatocellular carcinoma (HCC) remains unclear. Our objective was to examine the determinants of elevated serum VitB12 levels and their associations with prognosis of patients with HCC. The cohort study included 90

Ching-Yih Lin; Chang-Sheng Kuo; Chin-Li Lu; Meng-Ying Wu; Rwei-Fen Syu Huang



Change of Epigenetic Control of Cystathionine Beta-Synthase Gene Expression through Dietary Vitamin B12 Is Not Recovered by Methionine Supplementation  

Microsoft Academic Search

Background\\/Aims: Vitamin B12 (B-12) is an essential cofactor for methionine synthase, and methionine is critical for the methylation of various biological molecules including DNA. Whether changes in B-12 levels can alter specific gene expression through DNA methylation and whether dietary methionine has any effect on general DNA methylation status still remains controversial. Methods: We raised severely B-12-deficient rats as well

Atsushi Uekawa; Keishuke Katsushima; Asumi Ogata; Tetsunori Kawata; Nozomi Maeda; Ken-Ichi Kobayashi; Akio Maekawa; Tadahiro Tadokoro; Yuji Yamamoto



A case-control nutrigenomic study on the synergistic activity of folate and vitamin B12 in cervical cancer progression.  


The present study was designed to identify the role of folate, B12, homocysteine, and polymorphisms of methylene tetrahydrofolatereductase (MTHFR) gene in cervical carcinogenesis among 322 women from Kerala, South India. Serum folate, vitamin B12 (chemiluminescence assay), and homocysteine (EIA) along with genetic polymorphisms of MTHFR gene (polymerase chain reaction/restriction fragment length polymorphism) were analyzed for 136 control subjects, 92 low-grade squamous intraepithelial lesions (LSIL) subjects, and 94 invasive cervical cancer cases (ICC). Statistically significant associations between MTHFR polymorphisms, serum homocysteine, and folate levels with cervical carcinogenesis were not evident, but we found that these parameters acted as effect modifiers of serum vitamin B12. The risk estimates observed for B12 became prominent only when there was a deficiency in serum folate levels [LSIL-odds ratio (OR): 14.9 (95% CI: 2.65 to 84.4); ICC-OR = 8.72 (95% CI = 1.55 to 48.8)] or when MTHFR A1298C polymorphic variant was present [LSIL-OR = 9.8 (95% CI = 2.61 to 36.7); ICC-OR = 10.0 (95%CI = 2.5 to 39.3)]. The statistical significance of this effect modification was further studied using an interaction model, where only folate was observed to have an influence on B12 levels as suggested by the odds ratio of 7.11 (95% CI = 0.45 to 111.9) obtained for ICC group, implicating a synergistic role of these 2 vitamins in invasive cervical cancer. PMID:22519865

Ragasudha, Preethi N; Thulaseedharan, Jissa V; Wesley, Ramani; Jayaprakash, P G; Lalitha, Prema; Pillai, M Radhakrishna



Association between dietary intake of folate, vitamin B6, B12 & MTHFR, MTR Genotype and breast cancer risk  

PubMed Central

Objective: we conducted a case-control study to investigate the association between dietary folate, vitamin B6 and vitamin B12 intake, MTHFR and MTR genotype, and breast cancer risk. Methods: Genotyping for MTHFR C677T and A1298C and MTR A2756G polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) method. The intake of folate, vitamin B6 and vitamin B12 were calculated by each food item from questionnaire. Results: Subjects with breast cancer tended to have more first-degree relatives (?2=30.77, P<0.001) and have high intake of folate (t=2.42, P=0.008) and Vitamin B6 (t=2.94, P=0.002). Compared to the reference group, women with MTHFR 677 TT genotype and T allele had a significantly increased risk of breast cancer, with ORs (95%CI) of 1.8(1.08-2.27) and 1.39(1.02-1.92), respectively. For those who had folate intake?450 ug/day, MTHFR 667TT genotype was associated with a higher risk of breast cancer (OR=2.45, 95% CI=1.09-5.82, P=0.02). Similarly, subjects with Vitamin B6 intake?0.84 mg/day and MTHFR 667T allele genotype was correlated with a marginally increased risk of breast cancer. A significant interaction was observed between MTHFR C667T polymorphism and folate intake on the risk of breast cancer (P for interaction was 0.025). Conclusion: This case-control study found a significant association between MTHFR C667T polymorphism, folate intake and vitamin B6 and breast cancer risk, and a significant interaction was observed between MTHFR C667T polymorphism and folate intake on the risk of breast cancer.

Weiwei, Zheng; Liping, Chen; Dequan, Li



Association between dietary intake of folate, vitamin B6, B12 & MTHFR, MTR Genotype and breast cancer risk.  


Objective: we conducted a case-control study to investigate the association between dietary folate, vitamin B6 and vitamin B12 intake, MTHFR and MTR genotype, and breast cancer risk. Methods: Genotyping for MTHFR C677T and A1298C and MTR A2756G polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) method. The intake of folate, vitamin B6 and vitamin B12 were calculated by each food item from questionnaire. Results: Subjects with breast cancer tended to have more first-degree relatives (?(2) =30.77, P<0.001) and have high intake of folate (t=2.42, P=0.008) and Vitamin B6 (t=2.94, P=0.002). Compared to the reference group, women with MTHFR 677 TT genotype and T allele had a significantly increased risk of breast cancer, with ORs (95%CI) of 1.8(1.08-2.27) and 1.39(1.02-1.92), respectively. For those who had folate intake?450 ug/day, MTHFR 667TT genotype was associated with a higher risk of breast cancer (OR=2.45, 95% CI=1.09-5.82, P=0.02). Similarly, subjects with Vitamin B6 intake?0.84 mg/day and MTHFR 667T allele genotype was correlated with a marginally increased risk of breast cancer. A significant interaction was observed between MTHFR C667T polymorphism and folate intake on the risk of breast cancer (P for interaction was 0.025). Conclusion: This case-control study found a significant association between MTHFR C667T polymorphism, folate intake and vitamin B6 and breast cancer risk, and a significant interaction was observed between MTHFR C667T polymorphism and folate intake on the risk of breast cancer. PMID:24639841

Weiwei, Zheng; Liping, Chen; Dequan, Li



Hypomethylation of Serum Blood Clot DNA, but Not Plasma EDTA-Blood Cell Pellet DNA, from Vitamin B12-Deficient Subjects  

PubMed Central

Vitamin B12, a co-factor in methyl-group transfer, is important in maintaining DNA (deoxycytidine) methylation. Using two independent assays we examined the effect of vitamin B12-deficiency (plasma vitamin B12<148 pmol/L) on DNA methylation in women of childbearing age. Coagulated blood clot DNA from vitamin B12-deficient women had significantly (p<0.001) lower percentage deoxycytidine methylation (3.23±0.66%; n?=?248) and greater [3 H]methyl-acceptance (42,859±9,699 cpm; n?=?17) than DNA from B12-replete women (4.44±0.18%; n?=?128 and 26,049±2,814 cpm; n?=?11) [correlation between assays: r?=?–0.8538; p<0.001; n?=?28]. In contrast, uncoagulated EDTA-blood cell pellet DNA from vitamin B12-deficient and B12-replete women exhibited similar percentage methylation (4.45±0.15%; n?=?77 vs. 4.47±0.15%; n?=?47) and [3 H]methyl-acceptance (27,378±4,094 cpm; n?=?17 vs. 26,610±2,292 cpm; n?=?11). Therefore, in simultaneously collected paired blood samples, vitamin B12-deficiency was associated with decreased DNA methylation only in coagulated samples. These findings highlight the importance of sample collection methods in epigenetic studies, and the potential impact biological processes can have on DNA methylation during collection.

Zhu, Jiang-Hui; Maneval, David R.; Hao, Ling; Li, Zhu; Rasmussen, Sonja A.; Berry, R. J.; Bailey, Lynn B.



Ultrafast infrared spectral fingerprints of vitamin B12 and related cobalamins.  


Vitamin B(12) (cyanocobalamin, CNCbl) and its derivatives are structurally complex and functionally diverse biomolecules. The excited state and radical pair reaction dynamics that follow their photoexcitation have been previously studied in detail using UV-visible techniques. Similar time-resolved infrared (TRIR) data are limited, however. Herein we present TRIR difference spectra in the 1300-1700 cm(-1) region between 2 ps and 2 ns for adenosylcobalamin (AdoCbl), methylcobalamin (MeCbl), CNCbl, and hydroxocobalamin (OHCbl). The spectral profiles of all four cobalamins are complex, with broad similarities that suggest the vibrational excited states are related, but with a number of identifiable variations. The majority of the signals from AdoCbl and MeCbl decay with kinetics similar to those reported in the literature from UV-visible studies. However, there are regions of rapid (<10 ps) vibrational relaxation (peak shifts to higher frequencies from 1551, 1442, and 1337 cm(-1)) that are more pronounced in AdoCbl than in MeCbl. The AdoCbl data also exhibit more substantial changes in the amide I region and a number of more gradual peak shifts elsewhere (e.g., from 1549 to 1563 cm(-1)), which are not apparent in the MeCbl data. We attribute these differences to interactions between the bulky adenosyl and the corrin ring after photoexcitation and during radical pair recombination, respectively. Although spectrally similar to the initial excited state, the long-lived metal-to-ligand charge transfer state of MeCbl is clearly resolved in the kinetic analysis. The excited states of CNCbl and OHCbl relax to the ground state within 40 ps with few significant peak shifts, suggesting little or no homolysis of the bond between the Co and the upper axial ligand. Difference spectra from density functional theory calculations (where spectra from simplified cobalamins with an upper axial methyl were subtracted from those without) show qualitative agreement with the experimental data. They imply the excited state intermediates in the TRIR difference spectra resemble the dissociated states vibrationally (the cobalamin with the upper axial ligand missing) relative to the ground state with a methyl in this position. They also indicate that most of the TRIR signals arise from vibrations involving some degree of motion in the corrin ring. Such coupling of motions throughout the ring makes specific peak assignments neither trivial nor always meaningful, suggesting our data should be regarded as IR spectral fingerprints. PMID:22612868

Jones, Alex R; Russell, Henry J; Greetham, Gregory M; Towrie, Michael; Hay, Sam; Scrutton, Nigel S



Methionine, folic acid and vitamin B12 in growing-finishing pigs: impact on growth performance and meat quality.  


Growth performance, metabolic variables, and meat quality were measured in 78 growing-finishing pigs using supplements of 0 (C), or 0.2% of DL-methionine (M), and three combinations of folic acid [mg/kg] and cyanocobalamin [microg/kg], respectively 0 and 0 (V0), 10 and 25 (V1), and 10 and 150 (V2) in a 2 x 3 factorial arrangement. Feed conversion was lower (p = 0.05) in M than in C pigs during the growing period (0-4 weeks). Both V1 and V2 treatments increased plasma vitamin B12 (p < 0.01) and decreased plasma homocysteine (p < 0.01). Plasma 5-methyl-tetrahydrofolates were the lowest, highest and intermediate in V0, V1 and V2 pigs (p < 0.04), respectively. In V2 meat, folates were 32% higher, vitamin B12, 55% higher and homocysteine, 28% lower than in V0 (p < 0.01). Oxidative stability of the fresh meat was similar among treatments during a storage period of 42 days. Therefore, methionine supplements improved growth performance during the growing period. Vitamin supplements interacted with the methionine cycle pathway, increased vitamin content of pork meat but did not improve oxidative stability of the fresh meat during storage. PMID:18610535

Giguére, Alain; Girard, Christiane L; Matte, J Jacques



Validity and reproducibility of folate and vitamin B12 intakes estimated from a self-administered diet history questionnaire in Japanese pregnant women  

PubMed Central

Background No validated dietary questionnaire for assessing folate and vitamin B12 intakes during pregnancy is available in Japan. We evaluated the validity and reproducibility of intakes of folate and vitamin B12 estimated from a self-administered diet history questionnaire (DHQ) in Japanese pregnant women. Methods A sample of 167 healthy subjects with singleton pregnancies in the second trimester was recruited at a private obstetric hospital in metropolitan Tokyo from June to October 2008 (n = 76), and at a university hospital in Tokyo from June 2010 to June 2011 (n = 91). The dietary intakes of folate and vitamin B12 were assessed using the DHQ. The serum concentrations of folate and vitamin B12 were measured as reference values in the validation study. To assess the reproducibility of the results, 58 pregnant women completed the DHQ twice within 4-5 week interval. Results Significantly positive correlations were found between energy-adjusted intakes and serum concentrations of folate and vitamin B12 (r = 0.286, p < 0.001 and r = 0.222, p = 0.004, respectively). After excluding the participants with nausea (n = 121), the correlation coefficient for vitamin B12 increased to 0.313 (p = 0.001). When participants were classified into quintiles based on intakes and serum concentrations of folate and vitamin B12 , approximately 60% were classified in the same or adjacent quintile. The intraclass correlation coefficients of the two-time DHQ were 0.725 for folate and 0.512 for vitamin B12 . Conclusion The present study indicated that the DHQ had acceptable validity and reproducibility for assessing folate and vitamin B12 intakes in Japanese pregnant women.



[Clinical, biological and therapeutic profile of anemia by vitamin B12 deficiency in the department of hematology of Marrakech (Morocco)].  


The aim of this study is to examine retrospectively the clinical, biological and treatment features of anemia by vitamin B12 deficiency in the Hematology department of CHU Mohamed VI Marrakech. We report the results of a retrospective study conducted during six years (2005-2010). It included all patients with anemia (with or without thrombocytopenia or leukopenia) associated with vitamin B12 levels <200 pg / ml. One hundred twenty one cases were analyzed. The average age of patients was 62 years (38-89 years) with a female predominance (sex ratio F/M: 1.3). The clinical symptomatology is dominated by pallor (97.5%), cardiovascular signs (46%) and digestive symptoms (34.7%). Neurological signs were noted in 17.3% of cases. The blood count showed anemia (hemoglobin: mean= 6.9 g/dl), macrocythemia (MCV: mean= 109 fl). Leukopenia was noted in 35 patients (29%), thrombocytopenia in 34 patients (28%) and pancytopenia in 21 patients (17,3%). The average vitamin B12 was 72 pg/ml. The causes of B12 deficiency are pernicious anemia (43%), food-cobalamin malabsorption (43%), and in 14% of cases no etiology was found. Gastritis was found in 82.7% of our patients and Helicobacter pylori (HP) infection in 72.7% of cases. Reticulocyte crisis was observed after parenteral administration of hydroxocobalamine within an average of 8 days and normalization of blood counts, in all patients, within an average of 51 days. In patients with HP infection, eradication therapy of HP was performed. The cure rate of the HP is 90%. PMID:23536425

Nafil, H; Tazi, I; Sifessalam, M; Bouchtia, M; Mahmal, L



Are vitamin B 12 and folate deficiency clinically important after roux-en-Y gastric bypass?  

Microsoft Academic Search

Although iron, vltamm B12, and folate deficiency have been well documented after gastric bypass operations performed for morbid obesity, there is surprisingly\\u000a little information on either the natural course or the treatment of these deficiencies in Roux-en-Y gastric bypass (RYGB)\\u000a patients Durmg a l0-year period, a complete blood count and serum levels of iron, total iron-binding capacity, vltamin B12, and

R. E. Brolin; J. H. Gorman; R. C. Gorman; A. J. Petschenik; L. J. Bradley; H. A. Kenler; R. P. Cody



Folic Acid, Vitamin B6, and Vitamin B12 in Combination and Age-related Macular Degeneration in a Randomized Trial of Women  

PubMed Central

Context Observational epidemiologic studies indicate a direct association between homocysteine concentration in the blood and risk of age-related macular degeneration (AMD), but randomized trial data to examine the effect of homocysteine-lowering in AMD are lacking. Objective To examine incidence of AMD in a trial of folic acid/vitamin B6/vitamin B12. Design Randomized, double-masked, placebo-controlled trial. Participants 5,442 female health professionals aged 40 years or older with preexisting cardiovascular disease (CVD) or 3 or more CVD risk factors. A total of 5,205 of these women did not have a diagnosis of AMD at baseline and were included in this analysis. Intervention Participants were randomly assigned to receive a combination of folic acid (2.5 mg/d), vitamin B6 (50 mg/d), and vitamin B12 (1 mg/d), or placebo. Main Outcome Measures Total AMD, defined as a self-report documented by medical record evidence of an initial diagnosis after randomization, and visually-significant AMD, defined as confirmed incident AMD with visual acuity of 20/30 or worse attributable to this condition. Results After an average of 7.3 years of treatment and follow-up, there were 55 cases of AMD in the folic acid/B6/B12 group and 82 in the placebo group (relative risk [RR], 0.66; 95% confidence interval [CI], 0.47–0.93; p=0.02). For visually-significant AMD, there were 26 cases in the folic acid/B6/B12 group and 44 in the placebo group (RR, 0.59; 95% CI, 0.36–0.95; p=0.03). Conclusions These randomized trial data from a large cohort of women at high risk of CVD indicate that daily supplementation with folic acid/B6/B12 may reduce the risk of AMD.

Christen, William G.; Glynn, Robert J.; Chew, Emily Y.; Albert, Christine M.; Manson, JoAnn E.



Ultra-high performance liquid chromatographic and mass spectrometric analysis of active vitamin B12 in cells of Propionibacterium and fermented cereal matrices.  


A sensitive and selective method is needed to analyse in situ produced vitamin B12 in plant-based materials, potential new dietary sources of vitamin B12. A UHPLC/UV method was developed and validated for the determination of human active vitamin B12 in cell extracts of Propionibacterium freudenreichii subsp. shermanii and after immunoaffinity purification in extracts of cereal matrices fermented by P. freudenreichii. An Acquity HSS T3 C18 column resulted in a baseline separation, a calibration curve of excellent linearity and a low limit of detection (0.075ng/5?L injection). As confirmed by UHPLC-MS, the active vitamin B12 could be separated from pseudovitamin B12. The recovery of vitamin B12 from purified spiked cereal matrices was good (>90%; RSD<5%). A nutritionally relevant amount of active vitamin B12 was produced by P. freudenreichii in cereal malt matrices (up to 1.9?g/100g) in 24h at 28°C. PMID:25053103

Chamlagain, Bhawani; Edelmann, Minnamari; Kariluoto, Susanna; Ollilainen, Velimatti; Piironen, Vieno



Activities of various cobalamins for Euglena gracilis with reference to vitamin B12 assay with Euglena  

PubMed Central

Coenzyme B12 and methylcobalamin in water are less active in promoting growth of Euglena gracilis Z strain than the same concentrations of cyanocobalamin and hydroxocobalamin which are equally active. When bound to human serum or human liver homogenate, however, the activities of these four cobalamins do not differ significantly with one exception. The results suggest that the Euglena assay using cyanocobalamin standards is not satisfactory for quantitation of coenzyme B12 and methylcobalamin in water but acceptable when coenzyme B12 and methylcobalamin are bound to serum or liver. Sulphitocobalamin in water is as active as cyanocobalamin and hydroxocobalamin but nitritocobalamin is less active. Factor B, the monocarboxylic acids of cyanocobalamin and hydroxocobalamin, and the dicarboxylic acid of cyanocobalamin in water were inactive.

Adams, J. F.; McEwan, Fiona



Homocyst(e)ine, Folate, and Vitamin B12 Status in a Cohort of Welsh Young People Aged 12–13 Years Old  

Microsoft Academic Search

The aim of this unique study was to consider the relationship between folate and vitamin B12 on homocyst(e)ine (Hcy) concentration in an apparently healthy cohort of Welsh young people.A cohort of 179, 12–13 year olds (88 boys and 91 girls) were measured for Hcy, folate, vitamin B12, adiposity, and dietary habits.Boys had significantly higher waist circumference and folate concentration than

N. E. Thomas; S. M. Cooper; J. S. Baker; M. R. Graham; B. Davies



Influence of Training Volume and Acute Physical Exercise on the Homocysteine Levels in Endurance-Trained Men: Interactions with Plasma Folate and Vitamin B12  

Microsoft Academic Search

The interrelation between physical exercise and plasma levels of homocysteine (Hcy), vitamin B12, and folic acid has not been examined. Therefore, we investigated the influence of extensive endurance training and acute intense exercise on plasma concentrations of total Hcy, vitamin B12, and folic acid in 42 well-trained male triathletes. Examinations and blood sampling took place before and after a 30-day

D. König; E. Bissé; P. Deibert; H.-M. Müller; H. Wieland; A. Berg



Enantioselective outer-sphere complexation of lanthanide(III) tris (pyridine-2,6-dicarboxylate) chelates with vitamin B 12 derivatives. An NMR and CD study  

Microsoft Academic Search

The binding of three corrinoids, cyanocobalarnin (vitamin B12, CNCbl), aquacobalamin (vitamin B12a, H2OCbl+) and dicyanocobinamide ((CN)2Cbi), collectively denoted by Q, to the ?- and ?-enantiomer of Ln(DPA)33? complexes (Ln=lanthanide, DPA=2,6-pyridine dicarboxylate) in aqueous solution at room temperature is investigated by NMR and Circular Dichroism (CD) spectroscopy. Tb(DPA)33? induces shifts of the 1H-NMR resonances of Q. A formula, describing the dipolar

Stefan C. J. Meskers; Harry P. J. M. Dekkers



Vitamin B 12 , a chlorophyll-related analog to pheophytin a from marine brown algae, promotes neurite outgrowth and stimulates differentiation in PC12 cells  

Microsoft Academic Search

We previously isolated an analog to chlorophyll-related compounds, pheophytin a, from the marine brown alga Sargassum fulvellum and demonstrated that it is a neurodifferentiation compound. In the current study, we investigated the effects of the pheophytin\\u000a a analog vitamin B12 on PC12 cell differentiation. In the presence of a low level of nerve growth factor (10 ng ml?1), vitamin B12 demonstrated neurite

Atsutoshi Ina; Yuto Kamei



An effective and simplified pH-stat control strategy for the industrial fermentation of vitamin B 12 by Pseudomonas denitrificans  

Microsoft Academic Search

In order to improve the productivity of vitamin B12 by Pseudomonas denitrificans carried out in a 120-m3 fermenter, the effect of pH on vitamin B12 biosynthesis was investigated. Results obtained from shake flask experiments showed that the feeding of carbon source (beet\\u000a molasses or glucose) and methyl-group donor (betaine or choline chloride) significantly influenced the pH and the biosynthesis\\u000a of

Kun-Tai Li; Dong-Hong Liu; Ju Chu; Yong-Hong Wang; Ying-Ping Zhuang; Si-Liang Zhang



Maternal Folate and Vitamin B12 Status and Neural Tube Defects in Northern Iran: A Case Control Study  

PubMed Central

Objective This study was conducted to determine the serum level of folic acid and vitamin B12 in neural tube defects pregnancies (NTD) and healthy controls in Northern Iran. Methods This case-control study was performed on women with neural tube defects pregnancies and controls with unaffected pregnancies in Northern Iran during 2006. Twenty three pregnant women whose pregnancies were diagnosed as NTD by a second-trimester ultrasonographic examination were recruited as cases. The control group (n=23) consisted of women who were selected among socio-economic status (SES) matched women who had a normal targeted ultrasound during the second trimester with documented normal fet al outcome. Fetal NTD was suspected with targeted second-trimester ultrasound during the 16th week of gestation and confirmed with high maternal serum ?-fetoprotein levels. Folate, vitamin B12, homocysteine and alpha fetoprotein were evaluated after target ultrasonography. Findings Serum alpha fetoprotein level (mean±SD) in cases and controls was 120.2±64.1 and 50±33.5 iu/ml, respectively (P<0.05). The mean±SD folate in cases and controls was 8.4±4.2 versus 9.3±4.2 ng/ml, respectively. This difference was not significant. Folate deficiency was found in 30.4% of the cases and 13% of the controls (OR=2.9, 95%: 0.54–19.8). Vitamin B12 deficiency was found in 13% of cases and 17.7% of the controls (OR=0.7, 95%: 0.1-4.9). Conclusion This study showed that the probability of having a newborn with NTDs in maternal folate deficiency is three times higher than with normal folate in Northern Iran.

Mobasheri, Elahm; Keshtkar, Abbasali; Golalipour, Mohammad-Jafar



Socioeconomic factors are associated with folate and vitamin B12 intakes and related biomarkers concentrations in European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence study.  


Because socioeconomic factors (SEFs) may influence dietary quality and vitamin intakes, this study aimed to examine associations between socioeconomic factors and folate and vitamin B12 intakes as well as their related biomarkers in the Healthy Lifestyle in Europe by Nutrition in Adolescence study. Vitamin intakes were obtained from two 24-hour recalls in 2253 participants (47% males). Vitamin B biomarkers were assessed in a subsample of 977 participants (46% males). Socioeconomic factors were assessed by questionnaire, and 1-way analysis of covariance and linear regression analysis were applied. For males and females, mean intakes of folate were 211.19 and 177.18 ?g/d, and for vitamin B12, 5.98 and 4.54 ?g/d, respectively. Levels of plasma folate, red blood cell folate, serum B12, and holotranscobalamin were 18.74, 807.19, 330.64, and 63.04 nmol/L in males, respectively, and 19.13, 770.16, 377.9, and 65.63 nmol/L in females, respectively. Lower folate intakes were associated with several SEFs, including maternal and paternal education in both sexes. Regarding folate biomarkers, lower plasma folate intakes were associated with single/shared care in males and with lower paternal occupation in females. Lower vitamin B12 intakes were associated with almost all the studied SEFs, except paternal occupation in both sexes. In females, when considering vitamin B12 biomarkers, lower plasma vitamin B12 was associated with lower maternal education and occupation, and lower holotranscobalamin was associated with lower maternal education and lower paternal occupation. In conclusion, from the set of socioeconomic determinants studied in a sample of European adolescents, maternal education and paternal occupation were more consistently associated with folate and vitamin B12 intakes and biomarkers concentrations. PMID:24655486

Iglesia, Iris; Mouratidou, Theodora; González-Gross, Marcela; Novakovic, Romana; Breidenassel, Christina; Jiménez-Pavón, David; Huybrechts, Inge; De Henauw, Stefaan; Geelen, Anouk; Gottrand, Frédéric; Kafatos, Anthony; Mistura, Lorenza; de Heredia, Fátima Pérez; Widhalm, Kurt; Manios, Yanis; Molnar, Denes; Stehle, Peter; Gurinovic, Mirjana; Cavelaars, Adrienne E J M; Van't Veer, Pieter; Moreno, Luis A



An effective and simplified pH-stat control strategy for the industrial fermentation of vitamin B(12) by Pseudomonas denitrificans.  


In order to improve the productivity of vitamin B(12) by Pseudomonas denitrificans carried out in a 120-m(3) fermenter, the effect of pH on vitamin B(12) biosynthesis was investigated. Results obtained from shake flask experiments showed that the feeding of carbon source (beet molasses or glucose) and methyl-group donor (betaine or choline chloride) significantly influenced the pH and the biosynthesis of vitamin B(12). In contrast to beet molasses or choline chloride, using glucose as a feed medium and betaine as a methyl-group donor, pH could be maintained at a stable range. As a result, higher vitamin B(12) production was achieved. Accordingly, an effective and simplified pH-stat control strategy was established for the fermentation of vitamin B(12) in a 120-m(3) industrial fermenter. When the new pH control strategy was applied, pH was stably kept in the range of 7.15-7.30 during fermentation. Thus, 214.3 microg/mL of vitamin B(12) was achieved. PMID:18320234

Li, Kun-Tai; Liu, Dong-Hong; Chu, Ju; Wang, Yong-Hong; Zhuang, Ying-Ping; Zhang, Si-Liang



Effect of folate, vitamin B6, and vitamin B12 intake and MTHFR C677T polymorphism on homocysteine concentrations of renal transplant recipients.  


Plasma hyperhomocysteinemia (HHcy) is considered a risk factor for chronic allograft dysfunction (CAD), the main cause of functional loss in transplant recipients. Genetic polymorphisms that alter enzymes involved in homocysteine (Hcy) metabolism, such as methylenetetrahydrofolate reductase (MTHFR), and vitamin deficiency can result in HHcy. The objectives of this study were to investigate the relationship between HHcy and CAD development, and to evaluate the effect of intake of folate and vitamins B6 and B12 as well as MTHFR C677T polymorphism on Hcy concentrations. Ninety-eight renal transplant recipients including 48 showing CAD and 50 with normal renal function (NRF), were included in this cross-sectional study. Peripheral blood samples were collected for plasma Hcy quantification by liquid chromatography/sequential mass spectrometry (LC-MS/MS), and for MTHFR polymorphism analysis using polymerase chain reaction-restriction fragment length polymorphism. Dietary intake was evaluated using a nutritional questionnaire. HHcy (P=.002) and higher mean concentrations of Hcy (P=.029) were associated with CAD. An association was observed between HHcy and 677T variant allele in the CAD group (P=.0005). There was no correlation between Hcy concentration and folate, vitamin B6 or vitamin B12 intake in the CAD group. However, a negative correlation was observed between Hcy concentration and folate intake (P=.043), and also between Hcy concentration and vitamin B6 intake (P=.030) in the NRF group. According to our study, HHcy is associated with CAD development. In patients with CAD, MTHFR polymorphism seems to have a greater effect on the Hcy concentration than the vitamin intake. Increased folate and vitamin B6 intakes seem to reduce Hcy concentrations among transplant recipients with NRF, and could contribute to reducing the risk of CAD development. PMID:18089344

Biselli, P M; Sanches de Alvarenga, M P; Abbud-Filho, M; Ferreira-Baptista, M A S; Galbiatti, A L S; Goto, M T Y; Cardoso, M A; Eberlin, M N; Haddad, R; Goloni-Bertollo, E M; Pavarino-Bertelli, E C



Do folate, vitamins b6 and B12 play a role in the pathogenesis of migraine? The role of pharmacoepigenomics.  


Migraine is a neurovascular disease that has classically been attributed to multifactorial aetiologies, with genetic components and environmental interactions considered the main influence. Genes such as flavoenzyme 5, 10- methylenetetrahydrofolate reductase (MTHFR), especially the C677T variant, have been associated with elevated plasma homocysteine levels. This elevation in homocysteine results in an array of metabolic disorders and increased risk of complex diseases, including migraine. Catalysation of homocysteine requires the presence of vitamins B6, B12 and folate. Deficiencies in these cofactor vitamins result in hypomethylation, which triggers migraine. Because migraine predominantly affects females, it is hypothesised that fluctuating oestrogen levels, which are governed by oestrogen receptor 1 polymorphisms, are important. Another important factor is homocysteine, the production of which is dependent upon MTHFR and B vitamins. Gene expression is modulated through epigenetic mechanisms, which involve methionine. Additionally, folate plays a major role in DNA synthesis. We propose that vitamin B intake, coupled with MTHFR and oestrogen receptor 1 polymorphisms, causes differential DNA methylation and gene expression that may contribute to the occurrence of migraine. PMID:24040787

Shaik, Munvar Miya; Tan, Huay Lin; Kamal, Mohammad A; Gan, Siew Hua



Cytochemical studies of nuclear basic proteins in control and vitamin B12 starved Euglena.  


In avitaminosis B12, Euglena gracilis Z is blocked in the cell cycle in the S/G2 phase. In these blocked cells, transcription and traduction go on and the amount of DNA is less than doubled and remains constant during the blockage. Chromatin clumps observed in situ with classical electron microscopic methods are always condensed in control cells but are not visualized in B12 starved cells. Two cytochemical reactions, ethanolic phosphotungstic acid and ammoniacal silver reaction, specific for lysine- or arginine-rich residues, are performed to reveal basic nuclear proteins of chromatin. With these two methods, control chromatin in situ always shows a condensed aspect, whereas the starved chromatin appears dispersed. These cytochemical differences might be considered to result from a different supramolecular organization of the two kinds of chromatin. PMID:6411805

Bré, M H; Pouphile, M; Delpech, S; Lefort-Tran, M



MTHFR Polymorphisms Involved in Vitamin B 12 Deficiency Associated with Atrophic Gastritis  

Microsoft Academic Search

Genetic polymorphisms affecting methylentetrahydrofolate reductase (MTHFR) activity may influence hematological and neurological\\u000a dysfunction in cobalamin-deficient patients. We studied the prevalence of C677T and A1298C polymorphisms by analyzing genomic\\u000a DNA in 30 cobalamin-deficient patients. No significant difference was found in 677 and 1298 genotype distribution with respect\\u000a to hematological parameters, B12 and folate levels, and neurological symptoms. The two MTHFR polymorphisms

Mariangela Palladino; Patrizia Chiusolo; Giovanni Reddiconto; Sara Marietti; Daniela De Ritis; Giuseppe Leone; Simona Sica



A prospective study of folate, vitamin b6, and vitamin B12 intake in relation to exfoliation glaucoma or suspected exfoliation glaucoma.  


IMPORTANCE Effective strategies for primary prevention are lacking for exfoliation glaucoma (EG), which is the most common type of secondary glaucoma. OBJECTIVE To examine the association between B vitamin intake and EG or suspected EG (EG/SEG) risk. DESIGN, SETTING, AND PARTICIPANTS National prospective cohort study using more than 20 years of follow-up data from the Nurses' Health Study (all female registered nurses) and the Health Professionals Follow-up Study (all male health professionals) from June 1, 1980, to May 31, 2010 (Nurses' Health Study) and January 1, 1986, to December 31, 2010 (Health Professionals Follow-up Study). We included a subset of 78?980 Nurses' Health Study women and 41?221 Health Professionals Follow-up Study men who were 40 years or older, free of glaucoma, had completed diet questionnaires, and reported eye examinations (follow-up rate, >85%). EXPOSURES Cumulatively updated intake of B vitamins (folate, vitamin B6, and vitamin B12) as ascertained by repeated administration of validated questionnaires. MAIN OUTCOMES AND MEASURES Incident cases of EG/SEG, totaling 399 (329 women and 70 men), were first identified with the questionnaires and were subsequently confirmed with medical records. Multivariable relative risks for EG/SEG were calculated in each cohort and then pooled with meta-analysis. RESULTS Vitamin B6 and vitamin B12 intake was not associated with EG/SEG risk in pooled analyses (P?=?.52 and P?=?.99 for linear trend, respectively). However, a suggestive trend of a reduced risk was observed with higher intake of folate: compared with the lowest quintile of cumulatively averaged updated total folate intake, the multivariable relative risk for EG/SEG for the highest quintile (?654 ?g/d) was 0.75 (95% CI, 0.54-1.04; P?=?.02 for linear trend). These results were not materially altered after adjustment for vitamin B6 and vitamin B12 intake. An association was observed for supplemental folate intake but not for dietary folate only (P?=?.03 and P?=?.64 for linear trend, respectively). Greater frequency of multivitamin use showed a modest suggestive inverse association (current multivitamin use of ?6 times per week vs nonuse multivariable relative risk, 0.84; 95% CI, 0.64-1.11; P?=?.06 for linear trend). CONCLUSIONS AND RELEVANCE Higher total folate intake was associated with a suggestive lower risk for EG/SEG, supporting a possible causal role of homocysteine in EG/SEG. PMID:24699833

Kang, Jae H; Loomis, Stephanie J; Wiggs, Janey L; Willett, Walter C; Pasquale, Louis R



Prevalence of Vitamin B12 deficiency in patients of type 2 diabetes mellitus on metformin: A case control study from Pakistan  

PubMed Central

Introduction Diabetes Mellitus is the most common endocrine disorder and metformin is the most commonly prescribed oral hypoglycemic agent. Metformin is well known to cause viamin B12 deficiency due to effect on calcium-dependent membrane action in the terminal ileum leading to malabsorption of vitamin B12. The purpose of this study is to determine prevalence and associations of Vitamin B12 deficiency in patients of type 2 diabetes mellitus treated with metformin. Methods This case control study was carried out in department of medicine, Combined Military Hospital, Kharian from 1st Jan 2012 to 30 december 2012. We enrolled 114 outdoor patients of type 2 diabetes mellitus currently on metformin for atleast 12 months, by consecutive sampling, and 105 age and sex matched patients taken as control. Patients with vitamin B12 levels of less than 150 pg/ml were said to be B12 deficient. The results were analyzed on SPSS version 16. Results Serum B12 levels were low in 35 patients (31%) on metformin as compared to only 9 patients (8.6%) among controls,(p value 0.002). Mean B12 levels were significantly low in metformin group 311 pg/ml (±194.4), p value 0.03. Dose of metformin had inverse correlation with B12 levels and the difference was statistically significant with p-value < 0.001. Conclusion Our study demonstrated significantly high prevalence of vitamin B12 deficiency in patients treated with metformin with significant effect of dose and duration of metformin use on B12 levels. Physicians must recognize this important fact and screen diabetics on metformin therapy for underlying B12 deficiency.

Iftikhar, Raheel; Kamran, Sultan Mehmood; Qadir, Adnan; Iqbal, Zohaib; Usman, Hassan bin



Genetic and lifestyle factors related to the periconception vitamin B12 status and congenital heart defects: a Dutch case-control study.  


Maternal hyperhomocysteinemia is associated with congenital heart defects (CHDs) in the offspring. A low periconception vitamin B12 status is determined by genetic and lifestyle factors and causes hyperhomocysteinemia. We investigated methionine synthase reductase (MTRR) and transcobalamin II (TC) genes and maternal intake and serum concentrations of vitamin B12 in association with CHD risk. Seventeen months after the index-pregnancy, we studied 230 children with a CHD and 251 non-malformed children and their parents. Data were collected on current and periconception maternal vitamin supplement use and maternal dietary vitamin B12 intake of the month before the study moment. Blood samples were taken for the determination of MTRR A66G and TC C776G genotypes in families and maternal serum vitamin B12 concentrations. Transmission disequilibrium tests and univariate and multivariate analyses were applied. Allele transmissions were not significantly distorted. The MTRR and TC genotypes did not significantly affect CHD risk. Neither polymorphisms in mothers and/or children revealed significant interactions nor in combination with low vitamin B12 intake. Low maternal serum vitamin B12 combined with the maternal or child's MTRR 66 GG genotype resulted in odds ratios of 1.4 (95% confidence interval 0.6-3.5) and 1.3 (0.5-3.4), respectively. The TC 776 GG genotype in mothers and children revealed risk estimates of 2.2 (0.7-7.1) and 1.9 (0.5-7.4), respectively. In conclusion, MTRR 66 GG and TC 776 GG genotypes in mothers and children may contribute to the risk of CHDs, particularly when the maternal vitamin B12 status is low. The future enlargement of our sample size might demonstrate significant associations. PMID:18226574

Verkleij-Hagoort, Anna C; van Driel, Lydi M J W; Lindemans, Jan; Isaacs, Aaron; Steegers, Eric A P; Helbing, Willem A; Uitterlinden, André G; Steegers-Theunissen, Régine P M



Greater intake of vitamins B6 and B12 spares gray matter in healthy elderly: a voxel-based morphometry study  

PubMed Central

Previous studies have reported that high concentrations of homocysteine and lower concentrations of vitamin B6, B12, and folate increase the risk for cognitive decline and pathology in aging populations. In this cross-sectional study, high-resolution magnetic resonance imaging (MRI) scans and a 3-day food diary were collected on 32 community-dwelling adults between the ages of 59 and 79. We examined the relation between vitamin B6, B12, and folate intake on cortical volume using an optimized voxel-based morphometry (VBM) method and global gray and white matter volume after correcting for age, sex, body mass index, calorie intake, and education. All participants met or surpassed the recommended daily intake for these vitamins. In the VBM analysis, we found that adults with greater vitamin B6 intake had greater gray matter volume along the medial wall, anterior cingulate cortex, medial parietal cortex, middle temporal gyrus, and superior frontal gyrus, whereas people with greater B12 intake had greater volume in the left and right superior parietal sulcus. These effects were driven by vitamin supplementation and were negated when only examining vitamin intake from diet. Folate had no effect on brain volume. Furthermore, there was no relationship between vitamin B6, B12, or folate intake on global brain volume measures, indicating that VBM methods are more sensitive for detecting localized differences in gray matter volume than global measures. These results are discussed in relation to a growing literature on vitamin intake on age-related neurocognitive deterioration.

Erickson, Kirk I.; Suever, Barbara L.; Shaurya Prakash, Ruchika; Colcombe, Stanley J.; McAuley, Edward; Kramer, Arthur F.



Fermentation of a waste-product from the industrial processing of the lime ( Citrus aurantifolia swingle) for vitamin B 12 production  

Microsoft Academic Search

The purpose of this study was to investigate the possibility of utilizing the distillation residue, produced in the industrial processing of the lime, as a substrate for the production of vitamin B12 by Propionibacterium freudenreichii and Propionibacterium shermanii. Both microorganisms were found capable of fermenting the distillation residue with no significant differences in the production of this vitamin. However, P.

José Luis Pérez-Mendoza; Fernando García-Hernández



Determination of vitamin B12 in milk products and selected foods by optical biosensor protein-binding assay: method comparison.  


Biomolecular interaction analysis was evaluated for the automated determination of vitamin B12 in a range of foods. The analytical technique was configured as a biosensor-based, nonlabeled inhibition protein-binding assay using nonintrinsic R-protein. Sample extraction conditions were optimized, and both ligand specificity and nonspecific binding considerations were evaluated. Performance parameters included a quantitation range of 0.08-2.40 ng/mL, recoveries of 89-106%, agreement against assigned reference values for 3 independent certified food reference materials, and a mean between-laboratory reproducibility relative standard deviation of 4.9%. The proposed method was compared with reference microbiological and radioisotope protein-binding methods for a range of food samples. A wide selection of milks, infant formulas, meats, and liver were evaluated for their vitamin B12 content. The influence of season was studied in herd milk, early lactation was followed for a single animal, and the cobalamin content of bovine, caprine, and ovine milks was compared. PMID:11883401

Indyk, Harvey E; Persson, Bjorn S; Caselunghe, Malin C B; Moberg, Anna; Filonzi, Enrico L; Woollard, David C



Clinical study of tongue pain: Serum zinc, vitamin B12, folic acid, and copper concentrations, and systemic disease.  


The aim of this retrospective study of patients with tongue pain who showed no improvement after initial treatment and examination was to find out if their lack of response correlated with serum concentrations of zinc, vitamin B12, folic acid, and copper, and if it was associated with coexisting systemic diseases. We studied 311 patients for whom we had data about serum concentrations of these elements, and recorded whether they had any systemic diseases and were taking medicines regularly. One patient (0.3%) had a copper concentration outside the reference range; 2 patients (0.6%) had folic acid concentrations outside the reference range. The corresponding number for vitamin B12 was 5 (2%), and for zinc 30 (10%). The systemic diseases with the highest rates were: hyperlipidaemia (n=53, 17%), gastritis or gastric ulcer (n=51, 16%), angina pectoris (n=39, 13%), diabetes mellitus (n=31, 10%), thyroid disease (n=31, 10%), mild mental disorder (n=27, 9%), hypertension (n=18, 6%), cerebral infarction (n=17, 6%), leiomyoma (n=15, 5%) and anaemia (n=15, 5%). Roughly 10% of the patients were deficient in zinc. This study suggested that the serum concentration of zinc was most important to the patients with tongue pain. Many patients had more than one systemic condition, and all were taking various drugs. PMID:19735964

Yoshida, Hiroaki; Tsuji, Kaname; Sakata, Takeichi; Nakagawa, Akihito; Morita, Shosuke



Maternal dietary intake of folate and vitamins b6 and B12 during pregnancy and risk of childhood brain tumors.  


Childhood brain tumors (CBT) are the second most common childhood cancers, yet their etiology is largely unknown. We investigated whether maternal gestational intake of folate and vitamins B6 and B12 was associated with CBT risk in a nationwide case-control study conducted 2005-2010. Case children 0-14 years were recruited from all 10 Australian pediatric oncology centers. Control children were recruited by national random digit dialing, frequency matched to cases on age, sex, and state of residence. Dietary intake was ascertained using food frequency questionnaires and adjusted for total energy intake. Data from 293 case and 726 control mothers were analyzed using unconditional logistic regression. The odds ratio (OR) for the highest versus lowest tertile of folate intake was 0.70 [95% confidence interval (CI): 0.48, 1.02]. The ORs appeared lower in mothers who drank alcohol during pregnancy (OR = 0.45, 95% CI: 0.22, 0.93), mothers who took folic acid (OR = 0.67, 95% CI: 0.42, 1.06) or B6/B12 supplements (OR = 0.51, 95% CI: 0.25, 1.06) and in children younger than 5 years (OR = 0.50, 95% CI: 0.27, 0.93). These findings are consistent with folate's crucial role in maintenance of genomic integrity and DNA methylation. Dietary intake of B6 and B12 was not associated with risk of CBT. PMID:24897174

Greenop, Kathryn R; Miller, Margaret; de Klerk, Nicholas H; Scott, Rodney J; Attia, John; Ashton, Lesley J; Dalla-Pozza, Luciano; Bower, Carol; Armstrong, Bruce K; Milne, Elizabeth



Biological Variability and Impact of Oral Contraceptives on Vitamins B6, B12 and Folate Status in Women of Reproductive Age  

PubMed Central

Vitamins B6, B12 and folate play crucial metabolic roles especially during the reproductive years for women. There is limited reporting of within-subject variability of these vitamins. This study aimed to determine the within and between subject variability in serum vitamins B6, B12, folate and erythrocyte folate concentrations in young women; identify factors that contribute to variability; and determine dietary intakes and sources of these vitamins. Data were obtained from the control group of a trial aimed at investigating the effect of iron on the nutritional status of young women (age 25.2 ± 4.2 year; BMI 21.9 ± 2.2 kg/m2). The coefficients of variability within-subject (CVI) and between-subject (CVG) for serum vitamins B6, B12 and folate, and erythrocyte folate were calculated. Food frequency questionnaires provided dietary data. CVI and CVG were in the range 16.1%–25.7% and 31.7%–62.2%, respectively. Oral contraceptive pill (OCP) use was associated (P = 0.042) with lower serum vitamin B12 concentrations. Initial values were 172 ± 16 pmol/L and 318 ± 51 pmol/L for OCP and non-OCP users, respectively; with differences maintained at four time points over 12 weeks. BMI, age, physical activity, alcohol intake and haematological variables did not affect serum or erythrocyte vitamin concentrations. Vitamin B12 intakes were derived from traditional and unexpected sources including commercial energy drinks. Young women using OCP had significantly lower serum vitamin B12 concentrations. This should be considered in clinical decision making and requires further investigation.

McArthur, Jennifer O.; Tang, HoMan; Petocz, Peter; Samman, Samir



A preliminary investigation of the variation of vitamin B12 in oceanic and coastal waters  

Microsoft Academic Search

The presence in the sea of vitamin Bm or of its analogues, has been found necessary for the growth of several species of unicellular plants (e.g. Provasoli & Pintner, 1953; Droop, 1954, 1955). Bioassaysof the quantities in inshore waters during winter have been made by Lewin (1954)and by Droop (1954).The present investigation, carried out in 1955,wasdesigned to extend this study

C. B. Cowey



Identification of the btuCED polypeptides and evidence for their role in vitamin B12 transport in Escherichia coli.  

PubMed Central

Passage of vitamin B12 across the outer and cytoplasmic membranes of Escherichia coli occurs in two steps, each involving independent transport systems. Since the vitamin accumulated in btuC or btuD mutants is readily released from the cell by chase or osmotic shock and does not undergo the usual metabolic conversions, the products of these genes might participate in transport across the cytoplasmic membrane. Mutations in btuC and btuD are complemented by recombinant plasmids carrying a 3,410-base-pair HindIII-HincII DNA fragment. Transposon Tn1000 mutagenesis and subcloning defined the location of these two genes and showed that they are separated by approximately 800 base pairs. The polypeptides elicited by this fragment and its derivatives were identified by using a maxicell system. The apparent molecular weight of the btuC product was approximately 26,000, that of the btuD product was 29,000. Both polypeptides were associated with the cell membrane. Transposon insertions in the region between btuC and btuD, as well as those in the two genes, conferred a deficiency in vitamin B12 utilization and transport when they were crossed onto the chromosome. This region, termed btuE, encoded a 22,000-Mr polypeptide and lesser amounts of a 20,000-Mr species. A portion of the BtuE protein was released from maxicells by osmotic shock or spheroplast formation. The relative production of BtuE and BtuD in response to plasmids carrying transposon insertions suggested that the three genes are arranged in an operon in the order btuC-btuE-btuD and that internal promoters exist since polarity was incomplete. Substantial elevation of transport activity was engendered by plasmids carrying the intact btu region, but not when any of the btu genes was disrupted. The btuCED region thus may encode a transport system for passage of vitamin B12 across the cytoplasmic membrane. This system bears similarities to periplasmic binding protein-dependent transport systems, although the putative periplasmic component is not required for its function. Images

de Veaux, L C; Clevenson, D S; Bradbeer, C; Kadner, R J



Association of the B-Vitamins Pyridoxal 5'Phosphate (B6), B12, and Folate with Lung Cancer Risk in Older Men  

Microsoft Academic Search

A nested case-control study was conducted within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort to test for associations between selected B-vitamins (folate, vitamin B6, vitamin B12) and incident lung cancer. This trial was conducted in Finland between 1985 and 1993. Serum was analyzed for these nutrients and homocysteine among 300 lung cancer cases and matched controls (1:1). Odds ratios and

Terryl J. Hartman; Karen Woodson; Rachael Stolzenberg-Solomon; Jarmo Virtamo; Jacob Selhub; Michael J. Barrett; Demetrius Albanes


Net flux of nutrients across splanchnic tissues of lactating dairy cows as influenced by dietary supplements of biotin and vitamin B12.  


Biotin and vitamin B(12) are coenzymes in reactions that are essential to propionate metabolism in dairy cows. The objective of the present studies was to determine whether an increased dietary supply of these vitamins would change the net flux of nutrients through the rumen, the portal-drained viscera (PDV), the total splanchnic tissues (TSP), and the liver. Four lactating cows equipped with ultrasonic flow probes around the right ruminal artery and the portal vein and catheters in the right ruminal vein, the portal vein, one hepatic vein, and one mesenteric artery were fed 12 times per day a mixed ration at 95% of ad libitum dry matter intake. Daily supplements of 500 mg of vitamin B(12)+20mg of biotin or no vitamin supplement (study 1) or 500 mg of vitamin B(12) alone or with 20mg of biotin (study 2) were fed according to a crossover design with two 4-wk periods in each study. On the last day of each period, blood flow was recorded and blood samples were collected every 30 min for 4h. In study 1, biotin and vitamin B(12) given together increased milk production and milk protein yields compared with the control diet. The supplement increased appearance of the 2 vitamins across the PDV and TSP. It also reduced the net portal appearance of ammonia and total volatile fatty acids across the PDV. In study 2, compared with the 2 vitamins together, vitamin B(12) alone increased glucose flux across PDV and TSP as well as its arterial concentration and PDV flux of ammonia. With the diet used in the present experiment, the major effects of the vitamin supplements seem to be mediated through changes in ruminal fermentation and gastrointestinal tract metabolism rather than by effects on hepatic metabolism. PMID:20338442

Girard, C L; Desrochers, A



Effects of intramuscular injections of vitamin B12 on lactation performance of dairy cows fed dietary supplements of folic acid and rumen-protected methionine.  


The experiment was undertaken to determine the effects of i.m. injections of vitamin B(12) on lactational performance of primiparous dairy cows fed dietary supplements of folic acid and rumen-protected methionine from 4 to 18 wk of lactation. Fourteen primiparous Holstein cows were assigned to 7 blocks of 2 cows each, according to milk production during the third week of lactation. All cows were fed a basal diet supplemented daily with rumen-protected methionine (18 g of supplement, to bring the estimated supply of methionine to 2.2% of metabolizable protein) plus folic acid (4 mg per kg of BW). Within each block, the cows received a weekly i.m. injection (2 mL) of saline or 10 mg of vitamin B(12). Milk production was recorded daily. Milk and blood were sampled every 2 wk. Supplementary vitamin B(12) increased energy-corrected milk from 25.8 to 29.0 (SE 1.6) kg/d, as well as milk yields of solids [3.52 to 3.90 (SE 0.22) kg/d], fat [0.87 to 1.01 (SE 0.06) kg/d], and lactose [1.48 to 1.64 (SE 0.11) kg/d]. Supplementation also increased concentrations and amounts of vitamin B(12) secreted in milk but had no significant effect on dry matter intake and concentrations and amounts of folates in milk. Packed cell volume, blood hemoglobin, and serum vitamin B(12) were increased by supplementary vitamin B(12), whereas serum methylmalonic acid was decreased. Serum concentrations of sulfur amino acids were unchanged by treatment. These findings support the hypothesis that, in early lactation, supply of vitamin B(12) was not optimal and limited the lactation performance of the cows. PMID:15653534

Girard, C L; Matte, J J



Influence of methionine supply on the response of lactational performance of dairy cows to supplementary folic acid and vitamin B12.  


The present experiment was undertaken to determine if the effects of supplementary folic acid on lactational performance were caused by improved methylneogenesis and if the supply in vitamin B(12) could affect this metabolic pathway. In this eventuality, supplementary Met, a major source of preformed methyl groups, should reduce the requirements for these vitamins. Sixty multiparous Holstein cows were assigned to 10 blocks of 6 cows each according to their previous milk production. Within each block, 3 cows were fed a diet estimated to supply Met as 1.83% metabolizable protein and 3 cows were fed the same diet supplemented with 18 g of rumen-protected methionine (RPM) to supply Met as 2.23% of metabolizable protein. Within each level of Met, cows received no vitamin supplement or weekly intramuscular injections of 160 mg of folic acid alone or combined with 10 mg of vitamin B(12) from 3 wk before to 16 wk after calving. There was no treatment effect on dry matter intake during pre- and postcalving periods: 13.4 +/- 0.4 and 21.8 +/- 0.4 kg/d, respectively. Milk production was not affected by RPM supplementation. Folic acid and vitamin B(12) given together tended to increase milk production during the 16 wk of lactation. This effect was more pronounced during the first 4 wk of lactation: 37.5, 37.7, and 40.3 +/- 0.9 kg/d for cows receiving no vitamin supplement, folic acid alone, or folic acid combined with vitamin B(12), respectively. Milk fat yield was not affected by treatments. Lactose, crude protein, and total solid yields were greater, in early lactation, in cows injected with folic acid and vitamin B(12) together but this effect diminished as lactation progressed. Intramuscular injections of folic acid alone or combined with vitamin B(12) tended to decrease plasma concentrations of homocysteine from 5.51 microM with no vitamin supplement to 4.54 and 4.77 +/- 0.37 microM, respectively. Results of the present experiment suggest that the effects of the combined supplement of folic acid and vitamin B(12) on lactational performance of dairy cows were not due to an improvement in methyl groups supply, because RPM supplement, a source of preformed methyl groups, did not alter the cow responsiveness to vitamin supplements. PMID:19307650

Preynat, A; Lapierre, H; Thivierge, M C; Palin, M F; Matte, J J; Desrochers, A; Girard, C L



Study on solvent extraction of propionic acid from simulated discharged water in vitamin B12 production by anaerobic fermentation.  


The potential of recovering propionic acid from discharged water in vitamin B(12) production by anaerobic fermentation was investigated in this paper. A primary amine, N(1923), was used as the extractant, kerosene as diluter and n-octanol as modifier. The influences of the content of N(1923) in the organic phase, the phase ratio and the pH of aqueous phase on the extraction yield of propionic acid were studied. The organic phase composition with the volume ratio was proposed of N(1923):kerosene:n-octanol as 45:35:20. Under conditions of the phase ratio (o/w) as 1:4, the pH of aqueous phase of 3.0 and after 5 min extraction, the extraction yield of propionic acid can be over 97%. PMID:19201188

Wang, Kang; Chang, Zhidong; Ma, Yinchen; Lei, Chao; Wang, Jing; Zhu, Tingyu; Liu, Huizhou; Zuo, Yanjun; Li, Xin



Conformational cycle of the vitamin B12 ABC importer in liposomes detected by double electron-electron resonance (DEER).  


Double electron-electron resonance is used here to investigate intermediates of the transport cycle of the Escherichia coli vitamin B12 ATP-binding cassette importer BtuCD-F. Previously, we showed the ATP-induced opening of the cytoplasmic gate I in TM5 helices, later confirmed by the AMP-PNP-bound BtuCD-F crystal structure. Here, other key residues are analyzed in TM10 helices (positions 307 and 322) and in the cytoplasmic gate II, i.e. the loop between TM2 and TM3 (positions 82 and 85). Without BtuF, binding of ATP induces detectable changes at positions 307 and 85 in BtuCD in liposomes. Together with BtuF, ATP triggers the closure of the cytoplasmic gate II in liposomes (reported by both positions 82 and 85). This forms a sealed cavity in the translocation channel in agreement with the AMP-PNP·BtuCD-F x-ray structure. When vitamin B12 and AMP-PNP are simultaneously present, the extent of complex formation is reduced, but the short 82-82 interspin distance detected indicates that the substrate does not affect the closed conformation of this gate. The existence of the BtuCD-F complex under these conditions is verified with spectroscopically orthogonal nitroxide and Gd(III)-based labels. The cytoplasmic gate II remains closed also in the vanadate-trapped state, but it reopens in the ADP-bound state of the complex. Therefore, we suggest that the substrate likely trapped in ATP·BtuCD-F can be released after ATP hydrolysis but before the occluded ADP-bound conformation is reached. PMID:24362024

Joseph, Benesh; Korkhov, Vladimir M; Yulikov, Maxim; Jeschke, Gunnar; Bordignon, Enrica



The Effect of Vitamin B12 Infusion on Prevention of Nitrous Oxide-induced Homocysteine Increase: A Double-blind Randomized Controlled Trial  

PubMed Central

Objective Nitrous oxide is a common inhalation anesthetic agent in general anesthesia. While it is widely accepted as a safe anesthetic agent, evidence suggests exposure to this gas, leads to hyperhomocysteinemia. The present study aimed to evaluate the effects of single-dose intravenous infusions of vitamin B12, before and after the induction of nitrous oxide anesthesia on homocysteine levels after the surgery. Methods This double-blind randomized controlled trial was conducted on 60 patients who were scheduled for elective surgery under general anesthesia, presumably lasting for more than two hours. The subjects were randomly allocated to three groups of 20. For the first group, vitamin B12 solution (1 mg/100 ml normal saline) and 100 ml of normal saline (placebo), were infused before and after the induction of anesthesia, respectively. The second group received placebo and vitamin B12 infusion before and after the induction of anesthesia, respectively. The third group received placebo infusions at both times. Homocysteine levels were measured before and 24 hours after the surgery. Results The mean homocysteine and vitamin B12 levels were significantly different within the three groups (p<0.001). In patients who had been infused with vitamin B12 before the surgery, homocysteine levels were significantly lower than the other two groups. In the placebo group, homocysteine levels significantly increased after the surgery. Conclusion Nitrous oxide causes hyperhomocysteinemia after general anesthesia. Since vitamin B12 infusion is a safe and inexpensive method to decrease homocysteine levels in these patients, it may be recommended for patients undergoing nitrous oxide anesthesia to be used before induction of anesthesia.

Kiasari, Alieh Zamani; Firouzian, Abolfazl; Baradari, Afshin Gholipour; Nia, Hamid Sharif; Kiasari, Seyed Hosein Moosavi



Direct exchange of vitamin B12 is demonstrated by modelling the growth dynamics of algal-bacterial cocultures.  


The growth dynamics of populations of interacting species in the aquatic environment is of great importance, both for understanding natural ecosystems and in efforts to cultivate these organisms for industrial purposes. Here we consider a simple two-species system wherein the bacterium Mesorhizobium loti supplies vitamin B12 (cobalamin) to the freshwater green alga Lobomonas rostrata, which requires this organic micronutrient for growth. In return, the bacterium receives photosynthate from the alga. Mathematical models are developed that describe minimally the interdependence between the two organisms, and that fit the experimental observations of the consortium. These models enable us to distinguish between different mechanisms of nutrient exchange between the organisms, and provide strong evidence that, rather than undergoing simple lysis and release of nutrients into the medium, M. loti regulates the levels of cobalamin it produces, resulting in a true mutualism with L. rostrata. Over half of all microalgae are dependent on an exogenous source of cobalamin for growth, and this vitamin is synthesised only by bacteria; it is very likely that similar symbiotic interactions underpin algal productivity more generally. PMID:24522262

Grant, Matthew Aa; Kazamia, Elena; Cicuta, Pietro; Smith, Alison G



Anemia - B12 deficiency  


... alcoholism Crohn's disease , celiac disease , infection with the fish tapeworm, or other problems that make it difficult ... done include: Complete blood count (CBC ) Reticulocyte count LDH level Vitamin B12 level This list may not ...


Neuropathological and neuroprotective features of vitamin B12 on the dorsal spinal ganglion of rats after the experimental crush of sciatic nerve: an experimental study  

PubMed Central

Background Spinal motoneuron neuroprotection by vitaminB12 was previously reported; the present study was carried out to evaluate neuroprotectivity in the dorsal root ganglion sensory neuron. Methods In present study thirty-six Wister-Albino rats (aged 8–9 weeks and weighing 200–250 g) were tested. The animals were randomly divided into 6 groups which every group contained 6 rats. Group A: received normal saline (for 42 days); Group B: vitamin B12 was administered (0.5 mg/kg/day for 21 days); Group C: received vitamin B12 (1 mg/kg/day for 21days); Group D: received vitamin B12 (0.5 mg/kg/day for 42 days); Group E; received vitamin B12 (1 mg/kg/day for 42 days); Group F; received no treatment. The L5 Dorsal Root Ganglion (DRG) neurons count compared to the number of left and right neurons .Furthermore, DRG sensory neurons for regeneration were evaluated 21 or 42 days after injury (each group was analyzed by One-Way ANOVA test). Results (1): The comparison of left crushed neurons (LCN) number with right non-crushed neurons in all experimental groups (B, C, D and C), indicating a significant decline in their neurons enumeration (p<0/05). (2): The comparison of test group’s LCN with the control group’s LCN revealed a significant rise in the number of experimental group neurons (p<0/05). (3): Moreover, comparing the number of right neurons in experimental groups with the number of neurons in crushed neurons indicated that the average number of right neurons showed a significant increase in experimental groups (p<0/05). Conclusion Consequently, the probability of nerve regeneration will be increased by the increment of the administered drug dosage and duration. On the other hand, the regeneration and healing in Dorsal Spinal Ganglion will be improved by increase of administration time and vitamin B12 dose, indicating that such vitamin was able to progress recovery process of peripheral nerves damage in experimental rats. Finally, our results have important implications for elucidating the mechanisms of nerve regeneration. Moreover, the results showed that vitaminB12 had a proliferative effect on the dorsal root ganglion sensory neuron. Virtual slides The virtual slide(s) for this article can be found here:



Metabolic Vitamin B12 Status on a Mostly Raw Vegan Diet with Follow-Up Using Tablets, Nutritional Yeast, or Probiotic Supplements  

Microsoft Academic Search

Background: Pure vegetarian diets might cause cobalamin deficiency due to lack of dietary intake. It was hypothesized that a population following a vegan diet consuming mostly raw fruits and vegetables, carrot juice, and dehydrated barley grass juice would be able to avoid vitamin B12 deficiency naturally. Methods: Subjects were recruited at a health ministers’ reunion based on adherence to the

Michael S. Donaldson



Selective extraction and determination of vitamin B12 in urine by ionic liquid-based aqueous two-phase system prior to high-performance liquid chromatography.  


A rapid and simple extraction technique based on aqueous two-phase system (ATPS) was developed for separation and enrichment of vitamin B(12) in urine samples. The proposed ATPS-based method involves the application of the hydrophilic ionic liquid (IL) 1-hexyl-3-methylimidazolium chloride and K(2)HPO(4). After the extraction procedure, the vitamin B(12)-enriched IL upper phase was directly injected into the high performance liquid chromatography (HPLC) system for analysis. All variables influencing the IL-based ATPS approach (e.g., the composition of ATPS, pH and temperature values) were evaluated. The average extraction efficiency was 97% under optimum conditions. Only 5.0 mL of sample and a single hydrolysis/deproteinization/extraction step were required, followed by direct injection of the IL-rich upper phase into HPLC system for vitamin B(12) determination. A detection limit of 0.09 ?g mL(-1), a relative standard deviation (RSD) of 4.50% (n=10) and a linear range of 0.40-8.00 ?g mL(-1) were obtained. The proposed green analytical procedure was satisfactorily applied to the analysis of samples with highly complex matrices, such as urine. Finally, the IL-ATPS technique could be considered as an efficient tool for the water-soluble vitamin B(12) extraction. PMID:22841117

Berton, Paula; Monasterio, Romina P; Wuilloud, Rodolfo G



Insulin resistance and endothelial function are improved after folate and vitamin B12 therapy in patients with metabolic syndrome: relationship between homocysteine levels and hyperinsulinemia  

Microsoft Academic Search

Objective: The purpose of this study was (a) to study whether a folate and vitamin B12 treatment, aimed at decreasing homocysteine levels, might ameliorate insulin resistance and endothelial dys- function in patients with metabolic syndrome according to the National Cholesterol Education Pro- gram - Adult Treatment Panel-III criteria and (b) to evaluate whether, under these metabolic conditions, there is a

Emanuela Setola; Lucilla Domenica Monti; Elena Galluccio; Altin Palloshi; Gabriele Fragasso; Rita Paroni; Fulvio Magni; Emilia Paola Sandoli; Pietro Lucotti; Sabrina Costa; Isabella Fermo; Marzia Galli-Kienle; Anna Origgi; Alberto Margonato; PierMarco Piatti



Effects of Altered Maternal Folic Acid, Vitamin B12 and Docosahexaenoic Acid on Placental Global DNA Methylation Patterns in Wistar Rats  

Microsoft Academic Search

Potential adverse effects of excess maternal folic acid supplementation on a vegetarian population deficient in vitamin B12 are poorly understood. We have previously shown in a rat model that maternal folic acid supplementation at marginal protein levels reduces brain omega-3 fatty acid levels in the adult offspring. We have also reported that reduced docosahexaenoic acid (DHA) levels may result in

Asmita Kulkarni; Kamini Dangat; Anvita Kale; Pratiksha Sable; Preeti Chavan-Gautam; Sadhana Joshi; Takeo Yoshikawa



Effects of Altered Maternal Folic Acid, Vitamin B12 and Docosahexaenoic Acid on Placental Global DNA Methylation Patterns in Wistar Rats  

PubMed Central

Potential adverse effects of excess maternal folic acid supplementation on a vegetarian population deficient in vitamin B12 are poorly understood. We have previously shown in a rat model that maternal folic acid supplementation at marginal protein levels reduces brain omega-3 fatty acid levels in the adult offspring. We have also reported that reduced docosahexaenoic acid (DHA) levels may result in diversion of methyl groups towards DNA in the one carbon metabolic pathway ultimately resulting in DNA methylation. This study was designed to examine the effect of normal and excess folic acid in the absence and presence of vitamin B12 deficiency on global methylation patterns in the placenta. Further, the effect of maternal omega 3 fatty acid supplementation on the above vitamin B12 deficient diets was also examined. Our results suggest maternal folic acid supplementation in the absence of vitamin B12 lowers plasma and placental DHA levels (p<0.05) and reduces global DNA methylation levels (p<0.05). When this group was supplemented with omega 3 fatty acids there was an increase in placental DHA levels and subsequently DNA methylation levels revert back to the levels of the control group. Our results suggest for the first time that DHA plays an important role in one carbon metabolism thereby influencing global DNA methylation in the placenta.

Kulkarni, Asmita; Dangat, Kamini; Kale, Anvita; Sable, Pratiksha; Chavan-Gautam, Preeti; Joshi, Sadhana



Assignments in the Carbon-13 Nuclear Magnetic Resonance Spectra of Vitamin B12, Coenzyme B12, and Other Corrinoids: Application of Partially-Relaxed Fourier Transform Spectroscopy  

PubMed Central

High-resolution Fourier transform NMR at 15.08 MHz was used to observe the proton-decoupled natural-abundance 13C spectra of aqueous solutions of cobinamide dicyanide (0.067 M), cyanocobalamin (0.024 M), dicyanocobalamin (0.14 M), and coenzyme B12 (0.038 M). Assignments were made with the aid of chemical shift comparisons, off-resonance single-frequency proton decoupling, partially-relaxed Fourier transform spectra, and splittings arising from 13C-31P coupling. As expected, the 13C spectra of the coronoids were appreciably more informative than the corresponding proton spectra. Nearly all the lines in the 13C spectra of the corrinoids were well-resolved single-carbon resonances, in spite of the structural complexity. Partially relaxed 13C Fourier transform NMR spectra, which yield spin-lattice relaxation times of each resolved resonance, were found to be a very useful addition to the arsenal of NMR techniques.

Doddrell, David; Allerhand, Adam



Effect of Folic Acid and Vitamin B12 on Pemetrexed Antifolate Chemotherapy in Nutrient Lung Cancer Cells  

PubMed Central

Pemetrexed (MTA) is a multitargeted antifolate drug approved for lung cancer therapy. Clinically, supplementation with high doses of folic acid (FA) and vitamin B12 (VB12) lowers MTA cytotoxicities. An antagonistic effect of FA/VB12 on MTA efficacy has been proposed. However, patients who receive FA/VB12 show better tolerance to MTA with improved survival. The aims of this study are to investigate the modulation of FA and VB12 on MTA drug efficacy in human nonsmall cell lung cancer (NSCLC) cell lines. The sensitivities of cells, apoptosis, and MTA-regulated proteins were characterized to determine the possible effects of high doses of FA and VB12 on MTA efficacy. MTA has the lowest efficacy under 10% serum conditions. However, supplementation with FA and VB12 individually and additively reversed the insensitivity of NSCLC cells to MTA treatment with 10% serum. The enhanced sensitivities of cells following FA/VB12 treatment were correlated with increasing apoptosis and were specific to MTA but not to 5-fluorouracil (5-FU). Enhanced sensitivity was also associated with p21WAF1/Cip1 expression level. Our results revealed no antagonistic effect of high doses of FA/VB12 on MTA efficacy in cancer cells grown in nutrient medium. Furthermore, these data may partially explain why supplementation of FA and VB12 resulted in better survival in MTA-treated patients.

Yang, Tsung-Ying; Chang, Gee-Chen; Hsu, Shih-Lan; Huang, Yi-Rou; Chiu, Ling-Yen



How can cobalamin injections be spaced in long-term therapy for inborn errors of vitamin B(12) absorption?  


Inborn errors of cobalamin (Cbl, vitamin B(12)) absorption include hereditary intrinsic factor deficiency (HIFD) and Imerslund-Gräsbeck disease (IGD). HIFD is secondary to mutations in the HIF gene while IGD is due to mutations in one of the 2 subunits of the intrinsic factor receptor that is cubilin (CUBN) or amnionless (AMN). These disorders lead to intracellular Cbl depletion which in turn causes megaloblastic bone marrow failure, accumulation of homocysteine and methylmalonic acid (MMA), and methionine depletion. The clinical presentation reflects Cbl deficiency, with gastrointestinal symptoms, pancytopenia, and megaloblastic anemia. Mixed proteinuria, when it is present is strongly suggestive of IGD. Accurate diagnosis is always an emergency because early detection and treatment with life-long parenteral pharmacological doses of hydroxocobalamin are life saving and prevent further deterioration. However, the optimal frequency for cobalamin injections as a maintenance therapy is poorly reported. In order to evaluate the optimal maintenance schedule of cobalamin injections, we retrospectively collected clinical, biological, molecular and treatment data on 7 patients affected with congenital Cbl malabsorption. Unlike previous recommendations, we showed that a maintenance dosage of 1 mg cobalamin twice a year was enough to ensure a normal clinical status and keep the hematological and metabolic parameters in the normal range. These data suggest that patients affected with inborn errors of cobalamin absorption may be safely long-term treated with cobalamin injections every 6 months with careful follow-up of hematological and metabolic parameters. This maintenance regime is beneficial because the patients' quality of life improves. PMID:22854512

Boina Abdallah, Amina; Ogier de Baulny, Hélène; Kozyraki, Renata; Passemard, Sandrine; Fenneteau, Odile; Lebon, Sophie; Rigal, Odile; Mesples, Bettina; Yacouben, Karima; Giraudier, Stéphane; Benoist, Jean-François; Schiff, Manuel



Vitamin B(12) model complex catalyzed methyl transfer reaction to alkylthiol under electrochemical conditions with sacrificial electrode.  


Catalytic methyl transfer reactions from methyl tosylate to 1-octanethiol catalyzed by heptamethyl cobyrinate perchlorate, [Cob(II)7C(1)ester]ClO(4), were investigated under electrochemical conditions. As a model study for the cobalamin-dependent methyl transfer reaction from methyltetrahydrofolate to homocysteine, controlled-potential electrolyses were carried out at -1.0 V vs. Ag/AgCl using a zinc plate as the sacrificial anode at 50 degrees C in the dark. A turnover behaviour for the methyl transfer reaction was observed for the first time under non-enzymatic reaction conditions. Co(I) species, which is generated from the continuous electrolysis of [Cob(II)7C(1)ester]ClO(4), and its methylated CH(3)-Co complex were found to be important intermediates. The mechanism for such a methyl transfer reaction was investigated by product analysis, electronic spectroscopy and ESR spin-trapping experiments. A simple vitamin B(12) model complex was also utilized as the catalyst for the methyl transfer reaction. PMID:19885539

Pan, Ling; Shimakoshi, Hisashi; Masuko, Takahiro; Hisaeda, Yoshio



Selective intestinal malabsorption of vitamin B12 displays recessive Mendelian inheritance: Assignment of a locus to chromosome 10 by linkage  

SciTech Connect

Juvenile megaloblastic anemia caused by selective intestinal malabsorption of vitamin B12 has been considered a distinct condition displaying autosomal recessive inheritance. It appears to have a worldwide distribution, and comparatively high incidences were reported 30 years ago in Finland and Norway. More recently, the Mendelian inheritance of the condition has been questioned because almost no new cases have occurred in these populations. Here we report linkage studies assigning a recessive-gene locus for the disease to chromosome 10 in previously diagnosed multiplex families from Finland and Norway, proving the Mendelian mode of inheritance. The locus is tentatively assigned to the 6-cM interval between markers D10S548 and D10S466, with a multipoint maximum lod score (Z{sub max}) of 5.36 near marker D10S1477. By haplotype analysis, the healthy sibs in these families did not appear to constitute any examples of nonpenetrance. We hypothesize that the paucity of new cases in these populations is due either to a dietary effect on the gene penetrance that has changed with time, or to a drop in the birth rate in subpopulations showing enrichment of the mutation, or to both of these causes. 38 refs., 4 figs., 2 tabs.

Aminoff, M.; Tahvanainen, E.; Chapelle, A. de la [Univ. of Helsinki (Finland)] [and others



Mechanism of the ring contraction process in vitamin B12 biosynthesis by the anaerobe Propionibacterium shermanii under aerobic conditions.  


The mechanism of the ring contraction process during vitamin B(12) biosynthesis by the anaerobe Propionibacterium shermanii was investigated under both aerobic and anaerobic conditions by means of feeding experiments with delta-amino[1-(13)C]levulinic acid (a biosynthetic intermediate of tetrapyrrole) and delta-amino[1-(13)C,1,1,4-(18)O(3)]levulinic acid in combination with (13)C-NMR spectroscopy. We showed that the characteristic mechanism of the ring contraction process (the generation of precorrin-3x from formation of the gamma-lactone from the ring A acetate group at C1 and hydroxylation at C20 by molecular oxygen catalyzed by CobG, and the migration of ring D by cleavage of the carbon-oxygen bond at C1 of precorrin-3x) in the aerobe Pseudomonas denitrificans was not seen in P. shermanii under aerobic conditions, and the mechanism of the ring contraction process in P. shermanii was the same irrespective of the presence or absence of oxygen. PMID:17561959

Iida, Katsumi; Ohtaka, Kuniaki; Kajiwara, Masahiro



Seafood (wild and farmed) for the elderly: contribution to the dietary intakes of iodine, selenium, DHA and vitamins B12 and D.  


A large body of published data was analyzed to determine the concentrations of DHA, vitamins B12 and D, iodine, selenium in seafood (finfish and shellfish, wild and farmed, seawater and freshwater). The data on apparent consumption per inhabitant were taken from statistics prepared by OFIMER. This was used to determine the mean consumption of the main products of seafood in France in 2004 and the mean intakes of people aged 65 years and over. Not enough seafood is consumed by older people, according to the French recommended dietary allowances (french RDA), seafood provides 25% of the vitamin D RDA, 56% of the vitamin B12 RDA, 28% of iodine RDA, 23% of selenium RDA and 203% of DHA french RDA. For DHA, mean intake is aprox. 100% of international RDA. Seafood is the only class of food that provides major fractions of all these elements. We therefore recommend that older people increase their consumption of seafood to counteract the potential problems due to the low concentrations of these elements in their usual diets; this could overcome a potentially major public health problem. All elderly people would benefit from an increased intake of vitamin D and B12, iodine and selenium. Although some segments of the population seem not to lack DHA, others, such as those whose socio-economic positions or life styles restrict their seafood intakes, would benefit greatly from an increased intake of this omega-3 polyunsaturated fatty acid. PMID:18309439

Bourre, J M; Paquotte, P



Enantioselective excited-state quenching of racemic Tb (III) and Eu (III) Tris (pyridine-2,6-dicarboxylate) by vitamin B 12 derivatives  

Microsoft Academic Search

Enantioselectivity in the dynamic quenching of the luminescence of the ? and ? enantiomers of racemic Tb(III)(pyridine-2,6-dicarboxylate=DPA)33? and Eu(DPA)33? by a series of corrinoids is demonstrated by time resolved luminescence and circular-polarization-of-luminescence (CPL) spectroscopy. Studied are cyanocobalamin (vitamin B12), aquacobalamin (B12a) and its conjugated base hydroxocobalamin (HOCbl), dicyanocobinamide ((CN)2Cbi) and the heptamethyl ester of dicyanocobyrinic acid ((CN)2Cby(OMe)7). For this set

Stefan C. J. Meskers; Harry P. J. M. Dekkers



Measured Electron Spin Relaxation Rates in Frozen Solutions of Azurin, VITAMIN-B12R, and Nitrosyl Ferrous Myoglobin.  

NASA Astrophysics Data System (ADS)

Rates in frozen glycerin/water solutions at temperatures between 1.4 K and 20 K are reported for a copper-containing protein, azurin, and a cobalt-containing biomolecular complex, vitamin B_{rm 12r}, the paramagnetic product of the photolysis of coenzyme B_{12}. Results are interpreted in terms of a spectral dimensionality. Rates are also reported for nitrosyl ferrous myoglobin in frozen water solution, which exhibits a dominant one-phonon relaxation process up to 20 K and thus does not reveal spectral dimensionality. The anomalous variation of rate with temperature observed in several iron-containing proteins is not conspicuous here. In a model two-phonon mechanism of relaxation, temperature dependence is fixed by a spectral dimensionality, m, which specifies the variation of vibrational density of states with frequency rho(nu ) ~ nu ^{rm m-1} and is named in analogy with the Debye density of states in 1-, 2-, and 3-dimensional crystals. At sufficiently high temperatures, a non-resonant two-phonon process (Raman) should dominate the relaxation of a paramagnetic ion unless low-lying (under ^{~}70 cm^ {-1}) electronic states are present, as in many rare earths and in high spin ferric complexes, including many ferric proteins. The temperature dependence of the Raman rate for a Kramers ion (odd number of electrons) is T^{rm 3+2m} if temperature is sufficiently lower than Theta = hnu_{rm max} /k, the Debye temperature. The values of m from relaxation data on frozen solutions of a protein have sometimes been dependent upon solvent conditions. The maximum values of m for heme proteins, iron-sulfur proteins, and one copper -and-iron-containing protein, have ranged from about 1.3 to 1.8. Pulse saturation/recovery was used. The recoveries were not exponential, but rates were estimated from semilogarithmic displays of signals or from numerical fitting. The temperature dependence of the rates for azurin between 1.5 K and 22 K can be fit with a spectral dimensionality of 3 and a rather low Debye temperature near 69 K, in contrast to iron proteins. Relaxation of vitamin B_{ rm 12r} differed between samples, indicating varied photolysis or freezing. The Raman relaxation was well fit by a simple power law in temperature, but the values of m varied from 1.14 to 1.48 between samples.

Muench, Philip James


Effects of supplements of folic acid, vitamin B12, and rumen-protected methionine on whole body metabolism of methionine and glucose in lactating dairy cows.  


The present experiment was undertaken to determine the effects of dietary supplements of rumen-protected methionine and intramuscular injections of folic acid and vitamin B(12), given 3 wk before to 16 wk after calving, on glucose and methionine metabolism of lactating dairy cows. Twenty-four multiparous Holstein cows were assigned to 6 blocks of 4 cows each according to their previous milk production. Within each block, 2 cows were fed a diet estimated to supply methionine as 1.83% metabolizable protein, equivalent to 76% of methionine requirement, whereas the 2 other cows were fed the same diet supplemented daily with 18 g of rumen-protected methionine. Within each diet, the cows were administrated either no vitamin supplement or weekly intramuscular injections of 160 mg of folic acid plus 10 mg of vitamin B(12.) To investigate metabolic changes at 12 wk of lactation, glucose and methionine kinetics were measured by isotope dilution using infusions of 3[U-(13)C]glucose, [(13)C]NaHCO(3) and 3[1-(13)C,(2)H(3)] methionine. Milk and plasma concentrations of folic acid and vitamin B(12) increased with vitamin injections. Supplementary B-vitamins increased milk production from 34.7 to 38.9 +/- 1.0 kg/d and increased milk lactose, protein, and total solids yields. Whole-body glucose flux tended to increase with vitamin supplementation with a similar quantitative magnitude as the milk lactose yield increase. Vitamin supplementation increased methionine utilization for protein synthesis through increased protein turnover when methionine was deficient and through decreased methionine oxidation when rumen-protected methionine was fed. Vitamin supplementation decreased plasma concentrations of homocysteine independently of rumen-protected methionine feeding, although no effect of vitamin supplementation was measured on methionine remethylation, but this could be due to the limitation of the technique used. Therefore, the effects of these B-vitamins on lactation performance were not mainly explained by methionine economy because of a more efficient methylneogenesis but were rather related to increased glucose availability and changes in methionine metabolism. PMID:19164680

Preynat, A; Lapierre, H; Thivierge, M C; Palin, M F; Matte, J J; Desrochers, A; Girard, C L



The vitamin B12 analog cobinamide is an effective hydrogen sulfide antidote in a lethal rabbit model.  


Abstract Background and purpose. Hydrogen sulfide (H2S) is a highly toxic gas for which no effective antidotes exist. It acts, at least in part, by binding to cytochrome c oxidase, causing cellular asphyxiation and anoxia. We investigated the effects of three different ligand forms of cobinamide, a vitamin B12 analog, to reverse sulfide (NaHS) toxicity. Methods. New Zealand white rabbits received a continuous intravenous (IV) infusion of NaHS (3 mg/min) until expiration or a maximum 270 mg dose. Animals received six different treatments, administered at the time when they developed signs of severe toxicity: Group 1-saline (placebo group, N = 9); Group 2-IV hydroxocobalamin (N = 7); Group 3-IV aquohydroxocobinamide (N = 6); Group 4-IV sulfitocobinamide (N = 6); Group 5-intramuscular (IM) sulfitocobinamide (N = 6); and Group 6-IM dinitrocobinamide (N = 8). Blood was sampled intermittently, and systemic blood pressure and deoxygenated and oxygenated hemoglobin were measured continuously in peripheral muscle and over the brain region; the latter were measured by diffuse optical spectroscopy (DOS) and continuous wave near infrared spectroscopy (CWNIRS). Results. Compared with the saline controls, all cobinamide derivatives significantly increased survival time and the amount of NaHS that was tolerated. Aquohydroxocobinamide was most effective (261.5 ± 2.4 mg NaHS tolerated vs. 93.8 ± 6.2 mg in controls, p < 0.0001). Dinitrocobinamide was more effective than sulfitocobinamide. Hydroxocobalamin was not significantly more effective than the saline control. Conclusions. Cobinamide is an effective agent for inhibiting lethal sulfide exposure in this rabbit model. Further studies are needed to determine the optimal dose and form of cobinamide and route of administration. PMID:24716792

Brenner, M; Benavides, S; Mahon, S B; Lee, J; Yoon, D; Mukai, D; Viseroi, M; Chan, A; Jiang, J; Narula, N; Azer, S M; Alexander, C; Boss, G R



Water structure in vitamin B12 coenzyme crystals. I. Analysis of the neutron and x-ray solvent densities.  

PubMed Central

The disordered solvent distribution in crystals of vitamin B12 coenzyme was examined using the methods of high-resolution neutron and x-ray diffraction. One set of neutron (0.95 A) and two sets of x-ray (0.94 and 1.1 A) data were collected and the resulting models were extensively refined using least-squares and Fourier syntheses. The solvent regions were analyzed in two stages: first, main sites were assigned to the well defined regions of solvent density and refined using least squares; second, continuous sites were assigned representing the more disordered diffuse and elongated regions of solvent density. During the analysis an acetone molecule was also located. Water networks were formulated from the assigned sites in the above models and also from those assigned in the original structure determination (Lenhert, 1968), using criteria that included hydrogen bonding (derived from small crystal hydrates), van der Waals contact distances, side-chain disorder, water molecule orientations, and the presence or absence of foreign solvent. The well established networks extend throughout all the solvent regions of the crystal with interesting orientational arrangements of the individual waters around both polar and apolar groups of the coenzyme molecule. The networks were seen to be consistent among each of the four models in terms of occupying relatively similar positions. However, the occupancy values of the individual networks varied between the models; some networks were clearly visible in one but attenuated in another. The specific details of the water structure (bonding geometries, short-range nonbonded contacts, orientations of the waters, polar and apolar interactions, etc.) are described in the following paper. Images FIGURE 11 FIGURE 11b FIGURE 11c FIGURE 11b FIGURE 11e FIGURE 11f

Savage, H





... vitamins D and K. People who eat a vegetarian diet may need to take a vitamin B12 supplement. Each vitamin has specific jobs. If you have low levels of certain vitamins, you may get health problems. For example, if you don't get ...


Rapid resolution liquid chromatography method development and validation for simultaneous determination of homocysteine, vitamins B6, B9, and B12 in human serum  

PubMed Central

Aim: Hyperhomocysteinemia and vitamins B6, B9, and B12 deficiencies usually result in various neurological, vascular, ocular, renal, and pulmonary abnormalities. However, to date, there are no simultaneous detection methods available for determining homocysteine, vitamins B6, B9, and B12 levels in various biological fluids. In this study, we aim to develop a new validated simultaneous detection method for all four compounds to save both cost and time of analysis. Materials and Methods: The mobile phase consisted of a mixture of methanol and 1-heptanesulfonic acid sodium salt (33:67) with 0.05% triethylamine. The pH of the entire mixture was adjusted to 2.3 and the flow rate was 0.5 mL/min. Separation was achieved using a C-18 column (5 ?m; 150 mm × 4.6 mm) maintained at 28°C in a column oven and the detection was conducted at 210 nm. Results: The method was linear between 50 and 1600 ng/mL for all of the drugs. The limits of detection for homocysteine, vitamins B6, B9, and B12 were 5, 5, 10, and 10 ng/mL, respectively, while the limits of quantification were 10, 10, 25, and 25 ng/L, respectively. The developed method achieved good precision and accuracy and complies with the Food and Drug Administration (FDA) requirements. Conclusion: The developed and validated method is suitable to be used for the routine analysis of homocysteine, vitamins B6, B9, and B12 simultaneously in human serum.

Shaik, Munvar Miya; Gan, Siew Hua



Epidermal growth factor as a local mediator of the neurotrophic action of vitamin B12 (cobalamin) in the rat central nervous system  

Microsoft Academic Search

We have recently demonstrated that the myelinolytic lesions in the spinal cord (SC) of rats made deficient in vitamin B12 (cobalamin) (Cbl) through total gastrectomy (TG) are tumor necrosis factor-a (TNF-a)-mediated. We investigate whether or not permanent Cbl deficiency, induced in the rat either through TG or by chronic feeding of a Cbl-deficient diet, might modify the levels of three



Metabolic flux analysis of the central carbon metabolism of the industrial vitamin B 12 producing strain Pseudomonas denitrificans using 13C-labeled glucose  

Microsoft Academic Search

The network topology and metabolic fluxes of central carbon metabolism in the industrial vitamin B12 producing strain Pseudomonas denitrificans were characterized under oxygen limiting levels. Cultivations were carried out with 100% [1-13C] or 20% [U-13C] glucose as substrates under different oxygen supply conditions. The labeling patterns of the proteinogenic amino acids of exponentially growing cells were used to accurately estimate

Ze-Jian Wang; Ping Wang; Yu-Wei Liu; Yi-Ming Zhang; Ju Chu; Ming-zhi Huang; Ying-Ping Zhuang; Si-Liang Zhang


Methylenetetrahydrofolate reductase C677T genotype affects promoter methylation of tumor-specific genes in sporadic colorectal cancer through an interaction with folate\\/vitamin B12 status  

Microsoft Academic Search

AIM: To evaluate joint effects of Methylentetra- hydrofolate reductase (MTHFR ) C677T genotypes, and serum folate\\/vitamin B12 concentrations on promoter methylation of tumor-associated genes among Iranian colorectal cancer patients. METHODS: We examined the associations between MTHFR C677T genotype, and promoter methylation of P16 , hMLH1 , and hMSH2 tumor-related genes among 151 sporadic colorectal cancer patients. The promoter methylation of

Pooneh Mokarram; Fakhraddin Naghibalhossaini



Kenyan school children have multiple micronutrient deficiencies, but increased plasma vitamin B-12 is the only detectable micronutrient response to meat or milk supplementation.  


Animal source foods (ASF) can provide micronutrients in greater amounts and more bioavailable forms compared to plant source foods, but their intake is low in many poor populations. However, the impact of ASF on micronutrient status of undernourished populations has not been assessed. Supplemental meat (60-85 g/d), milk (200-250 mL/d) or energy (isocaloric with the meat and milk, 240-300 kcal/d) were randomly assigned to 555 undernourished school children aged 5-14 y in a rural malaria-endemic area of Kenya, at one school meal daily for one school year. Blood and stool samples were collected at baseline and after 1 y to assess stool parasites, malaria, hemoglobin, serum or plasma C-reactive protein, ferritin, iron, zinc, copper, vitamin B-12, folate and retinol, and erythrocyte riboflavin. At baseline, there was a high prevalence of micronutrient deficiencies (iron, zinc, vitamins A and B-12 and riboflavin), yet plasma ferritin was low in few children, and none had low serum copper. At the end of the year of supplementation, plasma vitamin B-12 concentrations were significantly increased in children fed the Meat or Milk meal; prevalence of severe plus moderate deficiency fell from 80.7% at baseline to 64.1% in the Meat group and from 71.6 to 45.1% in the Milk group, respectively. No significant improvement was observed in the status of other micronutrients compared to the Energy and Control groups, although malaria and other infections may have obscured effects. Supplementation with small amounts of meat or milk reduced the high prevalence of vitamin B-12 deficiency in these children. PMID:14672298

Siekmann, Jonathan H; Allen, Lindsay H; Bwibo, Nimrod O; Demment, Montague W; Murphy, Suzanne P; Neumann, Charlotte G



Prospective evaluation of protein bound vitamin B12 (cobalamin) malabsorption in the elderly using trout flesh labelled in vivo with 57Co-cobalamin  

PubMed Central

Background—The frequency of dietary protein bound vitamin B12 malabsorption in elderly patients remains controversial. ?Aims—To evaluate this malabsorption in elderly hospitalised patients using a modified Schilling test. ?Patients—Fourteen elderly patients with low B12 blood levels were prospectively selected from 394 hospitalised patients. ?Methods—The modified Schilling test was performed with trout labelled in vivo. ?Results—The test was normal in five healthy elderly subjects, in 7/8 patients with pancreatic insufficiency, and in nine non-elderly patients with antral gastritis. The low decision limit was established at 3.3% (median 4.8%). From the 14 elderly patients with low B12 prospectively selected from 394 hospitalised patients, seven had a real deficiency with anaemia and an increased homocysteine and/or methylmalonate serum level. The modified Schilling test showed malabsorption in five of these patients, including two in which the standard Schilling test was normal, and three in which the standard Schilling test was partially corrected by an intrinsic factor. ?Conclusions—Protein bound vitamin B12 malabsorption was detected in at least 0.5% of elderly hospitalised patients, using the labelled trout flesh absorption test. ?? Keywords: cobalamin deficiency; malabsorption; gastritis; Schilling test

Aimone-Gastin, I; Pierson, H; Jeandel, C; Bronowicki, J; Plenat, F; Lambert, D; Nabet-Belleville, F; Gueant, J



Red colored IgG4 caused by vitamin B12 from cell culture media combined with disulfide reduction at harvest.  


While many antibody therapeutics are formulated at low concentration (~10-20 mg/mL) for intravenous administration, high concentration (> 100 mg/mL) formulations may be required for subcutaneous delivery in certain clinical indications. For such high concentration formulations, product color is more apparent due to the higher molecular density across a given path-length. Color is therefore a product quality attribute that must be well-understood and controlled, to demonstrate process consistency and enable clinical trial blinding. Upon concentration of an IgG4 product at the 2000 L manufacturing scale, variability in product color, ranging from yellow to red, was observed. A small-scale experimental model was developed to assess the effect of processing conditions (medium composition and harvest conditions) on final bulk drug substance (BDS) color. The model was used to demonstrate that, for two distinct IgG4 products, red coloration occurred only in the presence of disulfide reduction-mediated antibody dissociation. The red color-causing component was identified as vitamin B 12, in the hydroxocobalamin form, and the extent of red color was correlated with the cobalt (vitamin B 12) concentration in the final pools. The intensity of redness in the final BDS was modulated by changing the concentration of vitamin B 12 in the cell culture media. PMID:24552690

Derfus, Gayle E; Dizon-Maspat, Jemelle; Broddrick, Jared T; Velayo, Arleene C; Toschi, Josh D; Santuray, Rodell T; Hsu, Stephen K; Winter, Charles M; Krishnan, Rajesh; Amanullah, Ashraf



Plasma and red cell reference intervals of 5-methyltetrahydrofolate of healthy adults in whom biochemical functional deficiencies of folate and vitamin B 12 had been excluded.  


5-Methyltetrahydrofolate (5-MTHF) is the predominant form of folate and a strong determinant of homocysteine concentrations. There is evidence that suboptimal 5-MTHF availability is a risk factor for cardiovascular disease independent of homocysteine. The analysis of folates remains challenging and is almost exclusively limited to the reporting of "total" folate rather than individual molecular forms. The purpose of this study was to establish the reference intervals of 5-MTHF in plasma and red cells of healthy adults who had been prescreened to exclude biochemical evidence of functional deficiency of folate and/or vitamin B12. Functional folate and vitamin B12 status was assessed by respective plasma measurements of homocysteine and methylmalonic acid in 144 healthy volunteers, aged 19-64 years. After the exclusion of 10 individuals, values for 134 subjects were used to establish the upper reference limits for homocysteine (13? ? mol/L females and 15? ? mol/L males) and methylmalonic acid (430?nmol/L). Subjects with values below these cutoffs were designated as folate and vitamin B12 replete and their plasma and red cell 5-MTHF reference intervals determined, N = 126: 6.6-39.9?nmol/L and 223-1041?nmol/L, respectively. The application of these intervals will assist in the evaluation of folate status and facilitate studies to evaluate the relationship of 5-MTHF to disease. PMID:24527038

Sobczy?ska-Malefora, Agata; Harrington, Dominic J; Voong, Kieran; Shearer, Martin J



Plasma and Red Cell Reference Intervals of 5-Methyltetrahydrofolate of Healthy Adults in Whom Biochemical Functional Deficiencies of Folate and Vitamin B12 Had Been Excluded  

PubMed Central

5-Methyltetrahydrofolate (5-MTHF) is the predominant form of folate and a strong determinant of homocysteine concentrations. There is evidence that suboptimal 5-MTHF availability is a risk factor for cardiovascular disease independent of homocysteine. The analysis of folates remains challenging and is almost exclusively limited to the reporting of “total” folate rather than individual molecular forms. The purpose of this study was to establish the reference intervals of 5-MTHF in plasma and red cells of healthy adults who had been prescreened to exclude biochemical evidence of functional deficiency of folate and/or vitamin B12. Functional folate and vitamin B12 status was assessed by respective plasma measurements of homocysteine and methylmalonic acid in 144 healthy volunteers, aged 19–64 years. After the exclusion of 10 individuals, values for 134 subjects were used to establish the upper reference limits for homocysteine (13??mol/L females and 15??mol/L males) and methylmalonic acid (430?nmol/L). Subjects with values below these cutoffs were designated as folate and vitamin B12 replete and their plasma and red cell 5-MTHF reference intervals determined, N = 126: 6.6–39.9?nmol/L and 223–1041?nmol/L, respectively. The application of these intervals will assist in the evaluation of folate status and facilitate studies to evaluate the relationship of 5-MTHF to disease.

Sobczynska-Malefora, Agata; Harrington, Dominic J.; Voong, Kieran; Shearer, Martin J.



B12 in fetal development  

Microsoft Academic Search

Vitamin B12 (cobalamin) is necessary for development of the fetus and child. Pregnant women who are vegetarian or vegan, have Crohn's or celiac disease, or have undergone gastric bypass surgery are at increased risk of B12 deficiency. Low serum levels of B12 have been linked to negative impacts in cognitive, motor, and growth outcomes. Low cobalamin levels also may be

M. Reese Pepper; Maureen M. Black



The synthesis of a corrole analogue of aquacobalamin (vitamin b12a) and its ligand substitution reactions.  


The synthesis of a Co(III) corrole, [10-(2-[[4-(1H-imidazol-1-ylmethyl)benzoyl]amino]phenyl)-5,15-diphenylcorrolato]cobalt(III), DPTC-Co, bearing a tail motif terminating in an imidazole ligand that coordinates Co(III), is described. The corrole therefore places Co(III) in a similar environment to that in aquacobalamin (vitamin B12a, H2OCbl(+)) but with a different equatorial ligand. In coordinating solvents, DPTC-Co is a mixture of five- and six-coordinate species, with a solvent molecule occupying the axial coordination site trans to the proximal imidazole ligand. In an 80:20 MeOH/H2O solution, allowed to age for about 1 h, the predominant species is the six-coordinate aqua species [H2O-DPTC-Co]. It is monomeric at least up to concentrations of 60 ?M. The coordinated H2O has a pKa = 9.76(6). Under the same conditions H2OCbl(+) has a pKa = 7.40(2). Equilibrium constants for the substitution of coordinated H2O by exogenous ligands are reported as log K values for neutral N-, P-, and S-donor ligands, and CN(-), NO2(-), N3(-), SCN(-), I(-), and Cys in 80:20 MeOH/H2O solution at low ionic strength. The log K values for [H2O-DPTC-Co] correlate reasonably well with those for H2OCbl(+); therefore, Co(III) displays a similar behavior toward these ligands irrespective of whether the equatorial ligand is a corrole or a corrin. Pyridine is an exception; it is poorly coordinated by H2OCbl(+) because of the sterically hindered coordination site of the corrin. With few exceptions, [H2O-DPTC-Co] has a higher affinity for neutral ligands than H2OCbl(+), but the converse is true for anionic ligands. Density functional theory (DFT) models (BP86/TZVP) show that the Co-ligand bonds tend to be longer in corrin than in corrole complexes, explaining the higher affinity of the latter for neutral ligands. It is argued that the residual charge at the metal center (+2 in corrin, 0 in corrole) increases the affinity of H2OCbl(+) for anionic ligands through an electrostatic attraction. The topological properties of the electron density in the DFT-modeled compounds are used to explore the nature of the bonding between the metal and the ligands. PMID:24721109

Zipp, Caitlin F; Michael, Joseph P; Fernandes, Manuel A; Mathura, Sadhna; Perry, Christopher B; Navizet, Isabelle; Govender, Penny P; Marques, Helder M



Phenylethynylcobalamin: a light-stable and thermolysis-resistant organometallic vitamin B(12) derivative prepared by radical synthesis.  


Don't take this antivitamin! 2-Phenylethynylcobalamin was prepared in a newly developed radical reaction using cob(II)alamin and 1-iodo-2-phenylethyne. It has an exceptionally short organometallic bond and is a remarkably light-stable and heat-resistant organometallic cobalamin. It is bound well by two important proteins of the human B12 transport system and has properties that are as expected for a new type of an "antivitamin?B12 ". PMID:24030966

Ruetz, Markus; Salchner, Robert; Wurst, Klaus; Fedosov, Sergey; Kräutler, Bernhard



Synthesis, characterization, Co-S bond reactivity of a vitamin B12 model complex having pentafluorophenylthiolate as an axial ligand.  


Heptamethyl (aquo)(pentafluorophenylthiolate)cobyrinate perchlorate, [(H2O)(C6F5S)Cob(III)7C1ester]ClO4, was synthesized as a B12 model complex having a thiolate ligand in the axial position. The axial ligand change in heptamethyl (diaquo)cobyrinate diperchlorate, [(H2O)2Cob(III)7C1ester](ClO4)2, from H2O to C6F5S(-) afforded the B12-thiolate complex. The B12-thiolate model complex was characterized by UV-vis, NMR and ESI-mass spectroscopies. The coordination of C6F5S(-) to the cobalt center affected the spectroscopic properties of the corrin ring through the electronic interaction between the axial ligand (C6F5S(-)) and the equatorial ligand (corrin). The photolysis of the B12-thiolate model complex led to the homolytic cleavage of the Co(iii)-S bond to form the Co(II) complex and the phenyl thiyl radical. The thermolysis of the B12-thiolate model complex also led to the homolytic cleavage of the Co(III)-S bond. Furthermore, the reactivity of the Co(III)-S bond of the B12-thiolate model complex was applied to the catalytic oxidation of C6F5SH to C6F5S-SC6F5. PMID:23463441

Tahara, Keishiro; Matsuzaki, Ayaka; Masuko, Takahiro; Kikuchi, Jun-ichi; Hisaeda, Yoshio



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. PMID:2070790

Stupperich, E; Nexø, E



Vitamin B12 regulates photosystem gene expression via the CrtJ antirepressor AerR in Rhodobacter capsulatus.  


The tetrapyrroles haem, bacteriochlorophyll and cobalamin (B12 ) exhibit a complex interrelationship regarding their synthesis. In this study, we demonstrate that AerR functions as an antirepressor of the tetrapyrrole regulator CrtJ. We show that purified AerR contains B12 that is bound to a conserved histidine (His145) in AerR. The interaction of AerR to CrtJ was further demonstrated in vitro by pull down experiments using AerR as bait and quantified using microscale thermophoresis. DNase I DNA footprint assays show that AerR containing B12 inhibits CrtJ binding to the bchC promoter. We further show that bchC expression is greatly repressed in a B12 auxotroph of Rhodobacter capsulatus and that B12 regulation of gene expression is mediated by AerR's ability to function as an antirepressor of CrtJ. This study thus provides a mechanism for how the essential tetrapyrrole, cobalamin controls the synthesis of bacteriochlorophyll, an essential component of the photosystem. PMID:24329562

Cheng, Zhuo; Li, Keran; Hammad, Loubna A; Karty, Jonathan A; Bauer, Carl E



Neural-tube defects are associated with low concentrations of cobalamin (vitamin B12) in amniotic fluid.  


While folate supplementation reduces the risk of recurrent neural-tube defects (NTD), both folate and cobalamin deficiencies may be independent risk-factors for neural-tube defects. Folate-dependence and impaired remethylation of homocysteine are implicated as mechanisms for NTD. There are few references reported for folate, cobalamin, homocysteine and methionine in the fetal compartment. This case-controlled pilot study of amniotic fluid (AF) samples derived from 16 NTD pregnancies and 64 age-matched controls quantities total homocysteine (tHcy), total cysteine (tCys), folate, cobalamin (B12), and methionine. Only decreased AF B12 concentrations were found (150 pg/ml versus 540 pg/ml, P < 0.02). Since cobalamin, folate and homocysteine participate in the remethylation of homocysteine, via methyl transfer from 5-methyltetrahydrofolate to B12, to methionine, we compared ratios of these methionine synthase (EC intermediates. The ratio of B12/folate for NTD versus controls was 48 (34-90) versus 126 (123-182), P < 0.001. The ratio of methionine/(folate x tHcy) was 1.4 (1.2-2.2) versus 2.7 (2.4-3.3), P < 0.001. We conclude that AF from pregnancies with NTD have lower B12 concentrations, and that ratios of product to substrate(s) of homocysteine remethylation suggest impaired methionine synthase in the fetal compartment through the early second trimester. PMID:9664599

Steen, M T; Boddie, A M; Fisher, A J; Macmahon, W; Saxe, D; Sullivan, K M; Dembure, P P; Elsas, L J



Metformin associated B12 deficiency.  


According to the ADA guidelines, metformin and lifestyle modifications are the first line therapies in the treatment of type 2 diabetes mellitus. Metformin does, however, cause vitamin B-12 malabsorption, which may increase the risk of developing vitamin B-12 deficiency--a clinically important and treatable condition. Here we report a case of 60 year old diabetic male presenting with clinical features of Vitamin B-12 deficiency on long term metformin therapy, which was confirmed on investigations. Patient showed symptomatic improvement with change in treatment. PMID:22799121

Kumthekar, Anand Ajit; Gidwani, Hitesh Vinod; Kumthekar, Ajit Bhaskar



Effect of inositol, lecithin, vitamins (B12 with choline and E), and iodinated casein on induced fatty liver-hemorrhagic syndrome in laying chickens.  


Egg production, liver lipid, and liver hemorrhagic score were not significantly altered by diets that contained inositol (at 1 or 2 g./kg. diet) and fed ad libitum, or force-fed to S.C. White Leghorn hens to produce fatty liver-hemorrhagic syndrome (FLHS). FLHS was not prevented by lecithin, iodinated casein alone or with inositol. The vitamins B12, choline and E appeared to reduce FLHS and liver lipid in the one group tested. The dose-response relationship between feed intake, liver hemorrhagic score and liver lipid content was again demonstrated. PMID:51496

Wolford, J H; Polin, D



Treatment of multiple sclerosis with lofepramine, L-phenylalanine and vitamin B(12): mechanism of action and clinical importance: roles of the locus coeruleus and central noradrenergic systems.  


In a randomized, placebo-controlled double-blind trial a combination of lofepramine, phenylalanine and vitamin B(12) was found to be effective in relieving the symptoms of multiple sclerosis (MS). The effect occurred within 2-4 weeks, and improved all types of symptoms in all types of MS. The combination was also effective in relieving symptoms in patients with chronic pain and chronic fatigue. We hypothesize that the action of this combined therapy may relate to activation of the noradrenergic locus coeruleus/lateral tegmentum (LC/LT) system which has the potential to influence the functioning of large areas of the brain and spinal cord. PMID:12376086

Loder, C; Allawi, J; Horrobin, D F



Is a low blood level of vitamin B12 a cardiovascular and diabetes risk factor? A systematic review of cohort studies  

Microsoft Academic Search

Purpose  To assess the prior hypothesis that low blood vitamin B12, partly through hyperhomocysteinemia and partly through direct effects,\\u000a increases the risk of cardiovascular diseases and diabetes. As background, we also extracted all-cause mortality from the\\u000a studies that met our criteria.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  A systematic review of prospective cohort studies identified through searching six electronic databases, screening of reference\\u000a lists, and citation search.

Snorri B. Rafnsson; Ponnusamy Saravanan; Raj S. Bhopal; Chittaranjan S. Yajnik



Clinical, nerve conduction and nerve biopsy study in vitamin B12 deficiency neurological syndrome with a short-term follow-up.  


Objective The frequency and type of neuropathy in vitamin B12 deficiency neurological syndrome (VBDNS) is controversial. This study reports the frequency and type of nerve dysfunction in VBDNS using nerve conduction and sural nerve biopsy and its response to treatment. Method Sixty-six patients with VBDNS diagnosed on the basis of low serum vitamin B12 level and/or megaloblastic bone marrow were subjected to clinical evaluation, hemoglobin, mean corpuscular volume, thyroid function test, HIV serology, and vasculitic profile. Peroneal motor and sural sensory nerve conduction studies were done. Sural nerve biopsy was done in six patients. The patients were treated with cyanocobalamin injection and followed up clinically and with nerve conduction study at 3 and 6 months. Results The median age of the patients was 46 (12-80) years and 11 patients were females. The duration of symptoms was 1-96 (median 7) months. Clinical features of neuropathy were present in 46 (69.7%) patients and nerve conduction was abnormal in 36 (54.5%) patients. On nerve conduction study, 8 (22.2%) patients had axonal, 4 (11.1%) had demyelinating, and 24 (66.7%) had mixed features. Nerve biopsy revealed acute axonal degeneration in early stage and chronic axonopathy with demyelination in the late stages of disease. The nerve conduction parameters improved at 6 months along with clinical recovery. Conclusion Nearly 70% patients with VBDNS had evidence of neuropathy which is mainly axonal with some demyelinating features. PMID:24256995

Kalita, Jayantee; Chandra, Satish; Bhoi, Sanjeev K; Agarwal, Ritu; Misra, Usha Kant; Shankar, Surala K; Mahadevan, Anita



Holotranscobalamins in B 12 and non B 12 requiring prokaryotes and eukaryotes  

Microsoft Academic Search

Transcobalamins, vitamin B12 binding proteins, deliver B12 to cell surface receptors which then permit B12 to cross cell membranes for metabolic use. There is little documentation concerning B12 binding proteins in bacteria and protists. We found that prokaryotes and eukaryotes requiring B12, as well as those protists synthesizing B12, also produce several transcobalamins for functionally transporting B12 similar to humans.

Herman Baker; Barbara DeAngelis; Marcelle Khalil; Oscar Frank; Elliott R. Baker




Microsoft Academic Search

Aims: Chronic alcohol exposure leads to a deficiency of group B vitamins and increased risk of alcoholic cardiomyopathy characterized by impaired ventricular contractility. This study was designed to examine the effect of group B vitamin supplementation on short-term exposure of the main alcohol metabolite acetaldehyde (ACA)-induced cardiac contractile dysfunction in rat ventricular myocytes. Methods: Mechanical contractile properties were evaluated by




Folate, but not vitamin B12 status, predicts respiratory morbidity in north Indian children1-5  

Microsoft Academic Search

Background: Vitamin deficiencies are often part of malnutrition, which predisposes to acute lower respiratory tract infections. Objective: The objective was to measure the association between cobalamin and folate status and subsequent respiratory morbidity. Design:Aprospectivecohortstudywasconductedin2482children aged 6-30 mo nested in a zinc supplementation trial. We measured plasma concentrations of folate, cobalamin, methylmalonic acid, and total homocysteine (tHcy) and followed the children

Tor A Strand; Sunita Taneja; Nita Bhandari; Helga Refsum; Per M Ueland; Håkon K Gjessing; Rajiv Bahl; Joern Schneede; Maharaj K Bhan; Halvor Sommerfelt


Enhanced application of square wave voltammetry with glassy carbon electrode coupled to multivariate calibration tools for the determination of B(6) and B(12) vitamins in pharmaceutical preparations.  


Vitamins B(6) (VB(6)) and B(12) (VB(12)) were simultaneously determined in pharmaceutical preparations by using square wave voltametry (SWV) together with artificial neural networks (ANNs). Supporting electrolyte solution, pH and voltametric technique were optimised. The calibration set was built with several artificial samples containing both active ingredients and excipients. Deviations from linearity were observed for both analytes. It is probably due to interactions among the electro active components and competition by the electrode surface, fact that supports the use of ANNs. Recoveries when analysing a nine sample validation set, of 100.2 and 96.4 were calculated for VB(6) and VB(12), respectively. Commercial samples were analysed with reasonably good results considering the complexity of the mixture studied. PMID:18969239

Hernández, Silvia R; Ribero, Gustavo G; Goicoechea, Héctor C



In vitro release studies of vitamin B 12 from poly N-vinyl pyrrolidone/starch hydrogels grafted with acrylic acid synthesized by gamma radiation  

NASA Astrophysics Data System (ADS)

Co-polymeric hydrogels containing N-vinyl pyrrolidone and starch grafted with acrylic acid were synthesized by gamma radiation to be used as drug delivery system. Their gel contents, grafting swelling and thermal gravimetric analysis were evaluated. The gel content increases by increasing the irradiation dose up to 50 kGy, then decreases. The grafting percent increases by the increasing of acrylic acid. The thermal stability and the rate of the thermal decomposition changed according to the different compositions. The maximum rate of the thermal decomposition decreases by increasing the irradiation dose from 20 to 30 kGy and increases by increasing the irradiation dose from 30 to 70 kGy. The hydrogels loaded with vitamin B 12 demonstrated a decrease release in acidic medium than the neutral one.

Eid, M.



The transcobalamin receptor knockout mouse: a model for vitamin B12 deficiency in the central nervous system.  


The membrane receptor (TCblR/CD320) for transcobalamin (TC)-bound cobalamin (Cbl) facilitates the cellular uptake of Cbl. A genetically modified mouse model involving ablation of the CD320 gene was generated to study the effects on cobalamin homeostasis. The nonlethal nature of this knockout and the lack of systemic cobalamin deficiency point to other mechanisms for cellular Cbl uptake in the mouse. However, severe cobalamin depletion in the central nervous system (CNS) after birth (P<0.01) indicates that TCblR is the only receptor responsible for Cbl uptake in the CNS. Metabolic Cbl deficiency in the brain was evident from the increased methylmalonic acid (P<0.01-0.04), homocysteine (P<0.01), cystathionine (P<0.01), and the decreased S-adenosylmethionine/S-adenosyl homocysteine ratio (P<0.01). The CNS pathology of Cbl deficiency seen in humans may not manifest in this mouse model; however, it does provide a model with which to evaluate metabolic pathways and genes affected. PMID:23430977

Lai, Shao-Chiang; Nakayama, Yasumi; Sequeira, Jeffrey M; Wlodarczyk, Bogdan J; Cabrera, Robert M; Finnell, Richard H; Bottiglieri, Teodoro; Quadros, Edward V



Effect of the vitamin B12-binding protein haptocorrin present in human milk on a panel of commensal and pathogenic bacteria  

PubMed Central

Background Haptocorrin is a vitamin B12-binding protein present in high amounts in different body fluids including human milk. Haptocorrin has previously been shown to inhibit the growth of specific E. coli strains, and the aim of the present study was to elucidate whether the antibacterial properties of this protein may exert a general defense against pathogens and/or affect the composition of the developing microbiota in the gastrointestinal tracts of breastfed infants. Findings The present work was the first systematic study of the effect of haptocorrin on bacterial growth, and included 34 commensal and pathogenic bacteria to which infants are likely to be exposed. Well-diffusion assays addressing antibacterial effects were performed with human milk, haptocorrin-free human milk, porcine holo-haptocorrin (saturated with B-12) and human apo-haptocorrin (unsaturated). Human milk inhibited the growth of S. thermophilus and the pathogenic strains L. monocytogenes LO28, L. monocytogenes 4446 and L. monocytogenes 7291, but the inhibition could not be ascribed to haptocorrin. Human apo-haptocorrin inhibited the growth of only a single bacterial strain (Bifidobacterium breve), while porcine holo-haptocorrin did not show any inhibitory effect. Conclusions Our results suggest that haptocorrin does not have a general antibacterial activity, and thereby contradict the existing hypothesis implicating such an effect. The study contributes to the knowledge on the potential impact of breastfeeding on the establishment of a healthy microbiota in infants.



B12 in fetal development.  


Vitamin B12 (cobalamin) is necessary for development of the fetus and child. Pregnant women who are vegetarian or vegan, have Crohn's or celiac disease, or have undergone gastric bypass surgery are at increased risk of B12 deficiency. Low serum levels of B12 have been linked to negative impacts in cognitive, motor, and growth outcomes. Low cobalamin levels also may be related to depression in adults. Some studies indicate that B12 supplementation may improve outcomes in children, although more research is needed in this area. Overall, the mechanisms of B12 action in development remain unclear. Further studies in this area to elucidate the pathways of cobalamin influence on development, as well as to prevent B12 deficiency in pregnant women and children are indicated. PMID:21664980

Pepper, M Reese; Black, Maureen M



Navigating the B12 Road: Assimilation, Delivery, and Disorders of Cobalamin*  

PubMed Central

The reactivity of the cobalt-carbon bond in cobalamins is the key to their chemical versatility, supporting both methyl transfer and isomerization reactions. During evolution of higher eukaryotes that utilize vitamin B12, the high reactivity of the cofactor coupled with its low abundance pressured development of an efficient system for uptake, assimilation, and delivery of the cofactor to client B12-dependent enzymes. Although most proteins suspected to be involved in B12 trafficking were discovered by 2009, the recent identification of a new protein reveals that the quest for elucidating the intracellular B12 highway is still far from complete. Herein, we review the biochemistry of cobalamin trafficking.

Gherasim, Carmen; Lofgren, Michael; Banerjee, Ruma



Neoproterozoic Oxygenation of Earth Surface Environments Reflected in the Late Evolution of the O2-Dependent Vitamin B12 Biosynthesis Pathway  

NASA Astrophysics Data System (ADS)

There are multiple lines of evidence for a significant rise of O2 in the Earth's atmosphere ~2.4 Ga. A second oxygenation event in the Neoproterozoic is not as well constrained. These changes in environmental redox affected the abundances of bioessential elements. Trace elements such as Co, Fe, and Ni were likely favored in the early evolution of metalloenzymes, prior to the first oxidation event. Consistent with this expectation, vitamin B12 is a Co-containing biomolecule whose biosynthesis is thought to have evolved prior to the origin of oxygenic photosynthesis and the first rise in O2. However, biochemical characterization of the many enzymes involved in B12 biosynthesis has revealed two distinct pathways: an O2-independent pathway and an O2-dependant pathway. The major difference between these pathways involves the timing of the insertion of Co. We examined the amino acid sequences of enzymes in the B12 biosynthesis pathway from a set of 100 phylogenetically diverse microbial genomes, focusing on enzymes exclusive to each pathway as well as enzymes shared by both. Molecular clock and phylogenetic analyses were performed on alignments of the sequences obtained from these study genomes. This approach focused on functional genes rather than the phylogeny of microbes in an attempt to understand the evolution of the pathway itself, rather than its presence in individual phylogenetic groups. Clear differences in age are apparent between representatives of each pathway. The O2-independent pathway and enzymes shared in both pathways show the most ancient last common ancestors. In contrast, the enzymes associated exclusively with the O2-dependent pathway diverged from a common ancestor less than a billion years ago. Phylogenetic analysis suggests that these enzymes were recruited from other biochemical pathways. From these results it seems likely that the evolution of the O2-dependent pathway occurred long after the initial evolution of the B12 biosynthesis. This conclusion provides evidence independent of the geological record as to the timing and existence of a second great oxidation event in Earth history.

Saito, M. A.; Bertrand, E. M.; Anbar, A.



Reversed-phase high-performance liquid chromatography method with coulometric electrochemical and ultraviolet detection for the quantification of vitamins B 1 (thiamine), B 6 (pyridoxamine, pyridoxal and pyridoxine) and B 12 in animal and plant foods  

Microsoft Academic Search

A rapid and sensitive high-performance liquid chromatography (HPLC) method with coulometric electrochemical and ultraviolet detections for analysis of vitamin B (B1, B6 and B12) in animal and plant foods has been developed. A combination of acid digestion and enzymatic extraction to release protein bound and phosphorylated vitamins followed by HPLC analysis was applied. The analyses were carried out on a

Anna Lebiedzi?ska; Marcin Leszek Marsza??; Jadwiga Kuta; Piotr Szefer



Efficacy of Multivitamin Supplementation Containing Vitamins B 6 and B 12 and Folic Acid as Adjunctive Treatment with a Cholinesterase Inhibitor in Alzheimer's Disease: A 26Week, Randomized, Double-Blind, Placebo-Controlled Study in Taiwanese Patients  

Microsoft Academic Search

BackgroundElevated serum homocysteine levels have been associated with the development of Alzheimer's dementia (AD). The combined use of a mecobalamin capsule preparation, which contains vitamin B12 0.5 mg with an active methyl base, and an over-the-counter nutritional supplement that contains folic acid 1 mg and pyridoxine hyperchloride 5 mg may be effective as a homocysteine-lowering vitamin regimen.ObjectiveThe aim of this

Yu Sun; Chien-Jung Lu; Kuo-Liong Chien; Sien-Tsong Chen; Rong-Chi Chen



Dietary Intake of Folate, but not Vitamin B 2 or B 12 , Is Associated with Increased Bone Mineral Density 5 Years after the Menopause: Results from a 10Year Follow-Up Study in Early Postmenopausal Women  

Microsoft Academic Search

Folate, vitamin B2 (riboflavin), and vitamin B12 may affect bone directly or through an effect on plasma homocysteine levels. Previously, a positive association has been found\\u000a between plasma levels and bone mineral density (BMD) as well as risk of fracture. However, there are limited data on whether\\u000a dietary intakes affect bone. Our aim was to investigate whether intake of folate,

L. Rejnmark; P. Vestergaard; A. P. Hermann; C. Brot; P. Eiken; L. Mosekilde



Atypical B12 Deficiency with Nonresolving Paraesthesia  

PubMed Central

Vitamin B12 deficiency can present with various hematological, gastrointestinal and neurological manifestations. We report a case of elderly female who presented with neuropathy and vitamin B12 deficiency where the final work-up revealed polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS). This case suggests that, although POEMS syndrome is a rare entity, it can present with vitamin-B12 deficiency and thus specific work up for early diagnosis of POEMS should be considered in patients with B12 deficiency unresponsive to therapy.

Haider, S.; Ahmad, N.; Anaissie, E. J.; Abdel Karim, N.



Comparative effect of low levels of dietary cobalt and parenteral injection of vitamin B(12) on carcass and meat quality characteristics in Omani goats.  


The effect of low levels of dietary cobalt (Co) on carcass and meat quality characteristics were investigated in 36 male goats of three different Omani breeds namely Batina, Dhofari and Jabal Akdhar. Goats were randomly divided into two groups at 10 weeks of age, control (18 animals) and treated (18 animals). Goats from both groups were fed Rhodesgrass hay and a commercially prepared diet containing 0.10 and 0.12 mg Co/kg DM, respectively from 10 to 46 weeks of age. Animals in the treated group were supplemented with subcutaneous injections of 2000 ?g of hydroxocobalamin (vitamin B(12)) on week 10 and thereafter for 46 weeks at 8-week intervals. At 46 weeks of age, the animals were slaughtered and their carcass and meat quality characteristics compared. Serum vitamin B(12) levels were significantly higher in goats from the treated group from week 16 till the end of the experiment. The final live and carcass weights were significantly higher (P<0.05) for the treated Batina group by 13.4 and 8.3% compared with the control group, respectively. Shoulder, rack, loin and leg cut weights were also significantly higher (P<0.05) for the Batina treated group compared with the control group by 14.7, 16.8, 12.8 and 13.1%, respectively. Carcass length, leg length, width behind shoulder, maximum shoulder width and longissimus muscle area were significantly higher (P<0.05) for the Batina treated breed than for the control group by 6.7, 5.8, 10.1, 10.1 and 28.5%, respectively. Four muscles (Mm. longissimus dorsi, biceps femoris, semimembranosus, and semitendinosus) from treated and control groups were evaluated for ultimate pH, expressed juice, cooking loss%, colour (L*, a* and b*), and Warner-Bratzler shear force values. There were significant treatment effects on these muscle quality characteristics for the Batina breed only. Muscles from the treated group showed significantly lower (P<0.05) shear force values of between 15 and 27% than those from the control group. Moreover, the treated Batina goats tended to have significantly lower (P<0.05) ultimate pH, expressed juice, L* and higher a* values than those from the control group for longissimus dorsi and biceps femoris muscles only. PMID:22061016

Kadim, I T; Mahgoub, O; Srikandakumar, A; Al-Ajmi, D S; Al-Maqbaly, R S; Al-Saqri, N M; Johnson, E H



Enantioselective excited-state quenching of racemic Tb (III) and Eu (III) Tris (pyridine-2,6-dicarboxylate) by vitamin B 12 derivatives  

NASA Astrophysics Data System (ADS)

Enantioselectivity in the dynamic quenching of the luminescence of the ? and ? enantiomers of racemic Tb(III)(pyridine-2,6-dicarboxylate=DPA) 33- and Eu(DPA) 33- by a series of corrinoids is demonstrated by time resolved luminescence and circular-polarization-of-luminescence (CPL) spectroscopy. Studied are cyanocobalamin (vitamin B 12), aquacobalamin (B 12a) and its conjugated base hydroxocobalamin (HOCbl), dicyanocobinamide ((CN) 2Cbi) and the heptamethyl ester of dicyanocobyrinic acid ((CN) 2Cby(OMe) 7). For this set of quenchers (Q), the diastereomeric quenching rate constants ( kq? and kq?) are reported together with the degree of enantioselectivity Eq=( kq?- kq?)/( kq?+ kq?). In the systems with Tb, values of the average rate constant kqavg(=( kq?+ kq?)/2) are 1.0, 2.9 and 0.53 10 8 M -1 s -1 for CNCbl, (CN) 2Cbi, (CN) 2Cby(OMe) 7 with Eq=-0.24, -0.20, +0.01 (standard error of Eq is 0.01). The quenching by B 12a is strongly dependent on pH and ionic strength ( I); when I=12 mM we find kqavg=5.3, Eq=-0.23 at pH 6.7 and kqavg=1.3, Eq=-0.27 at pH 8.9. Corresponding rates for Eu are 0.41, 27, 3.4 10 7 M -1 s -1 and for B 12a, 7.3 and 1.2 10 7 M -1 s -1, corresponding values for Eq -0.27, -0.29, +0.02, -0.21 and -0.29. The quenching reaction is modeled as a pre-equilibrium involving the formation of an encounter complex (association constant K) followed by the actual electronic energy transfer step (rate ket). By relating the quenching data with molecular structure it is argued that the binding in the encounter complex involves two hydrogen bonds between the uncoordinated carboxylate oxygen atom of two DPA ligands of Ln(DPA) 33- and two amide groups of the corrinoid, presumably involving the a and g, the a and b, or the b and g side chains. For some corrinoid/Ln(DPA) 33- complexes the association constants and enantioselectivities in the ground state are known (Spectrochimica Acta 55A (1999) 1837-1855), which allows for an estimate of the average rate of energy transfer, ketavg (i.e. ( ket?+ ket?)/2). The enantioselectivity in the quenching reaction is lower than in the ground state association which is interpreted in terms of different values of ket in the two diastereomeric Ln-corrinoid complexes; for both Tb and Eu we find ket?/ ket?˜0.3 with CNCbl, B 12a at pH 6.7 and (CN) 2Cbi. These data imply that the chiral discrimination in the energy transfer is considerable and counteracts that in the binding but does not dominate it.

Meskers, Stefan C. J.; Dekkers, Harry P. J. M.



Expression of Genes Encoding Enzymes Involved in the One Carbon Cycle in Rat Placenta is Determined by Maternal Micronutrients (Folic Acid, Vitamin B12) and Omega-3 Fatty Acids  

PubMed Central

We have reported that folic acid, vitamin B12, and omega-3 fatty acids are interlinked in the one carbon cycle and have implications for fetal programming. Our earlier studies demonstrate that an imbalance in maternal micronutrients influence long chain polyunsaturated fatty acid metabolism and global methylation in rat placenta. We hypothesize that these changes are mediated through micronutrient dependent regulation of enzymes in one carbon cycle. Pregnant dams were assigned to six dietary groups with varying folic acid and vitamin B12 levels. Vitamin B12 deficient groups were supplemented with omega-3 fatty acid. Placental mRNA levels of enzymes, levels of phospholipids, and glutathione were determined. Results suggest that maternal micronutrient imbalance (excess folic acid with vitamin B12 deficiency) leads to lower mRNA levels of methylene tetrahydrofolate reductase (MTHFR) and methionine synthase , but higher cystathionine b-synthase (CBS) and Phosphatidylethanolamine-N-methyltransferase (PEMT) as compared to control. Omega-3 supplementation normalized CBS and MTHFR mRNA levels. Increased placental phosphatidylethanolamine (PE), phosphatidylcholine (PC), in the same group was also observed. Our data suggests that adverse effects of a maternal micronutrient imbalanced diet may be due to differential regulation of key genes encoding enzymes in one carbon cycle and omega-3 supplementation may ameliorate most of these changes.

Khot, Vinita; Kale, Anvita; Joshi, Asmita; Chavan-Gautam, Preeti; Joshi, Sadhana



A phase II study of pralatrexate with vitamin B12 and folic acid supplementation for previously treated recurrent and/or metastatic head and neck squamous cell cancer.  


Background Pralatrexate (Fotolyn(TM); Allos Therapeutics Inc.) is an antifolate dihydrofolate reductase (DHFR) inhibitor. We conducted a phase II study of pralatrexate with folic acid and B12 supplementation in patients with recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC). Patients and methods This was a single-arm, Simon optimal two stage phase II study. Patients with R/M HNSCC previously treated with chemotherapy were eligible. The study was initiated with a dosing schedule of pralatrexate 190 mg/m(2) biweekly on a 4-week cycle with vitamin supplementation. Due to toxicity concerns, the dosing was modified to 30 mg/m(2) weekly for 3 weeks in a 4-week cycle with vitamin supplementation. Radiologic imaging was to be obtained about every 2 cycles. Results Thirteen subjects were enrolled; 12 were treated. Seven of the twelve patients had previously received ?2 lines of chemotherapy. The most common grade 3 toxicity was mucositis (3 patients). Seven patients did not complete two cycles of therapy due to progression of disease (4), toxicity (1), death (1), and withdrawal of consent (1). Two deaths occurred: one due to disease progression and the other was an unwitnessed event that was possibly related to pralatrexate. No clinical activity was observed. The median overall survival was 3.1 months. The study was closed early due to lack of efficacy. Conclusions Pralatrexate does not possess clinical activity against previously treated R/M HNSCC. Evaluation of pralatrexate in other clinical settings of HNSCC management with special considerations for drug toxicity may be warranted. PMID:24566705

Ho, Alan L; Lipson, Brynna L; Sherman, Eric J; Xiao, Han; Fury, Matthew G; Apollo, Arlyn; Seetharamu, Nagashree; Sima, Camelia S; Haque, Sofia; Lyo, John K; Sales, Roberta; Cox, Lisa; Pfister, David G



Indian women with higher serum concentrations of folate and vitamin B12 are significantly less likely to be infected with carcinogenic or high-risk (HR) types of human papillomaviruses (HPVs)  

PubMed Central

Background: Studies conducted in the USA have demonstrated that micronutrients such as folate and vitamin B12 play a significant role in modifying the natural history of high-risk human papillomaviruses (HR-HPVs), the causative agent for developing invasive cervical cancer (CC) and its precursor lesions. Objective: The purpose of the current study was to investigate whether these micronutrients have similar effects on HR-HPV infections in Indian women. Methods: The associations between serum concentrations of folate and vitamin B12 and HR-HPV infections were evaluated in 724 women who participated in a CC screening study in the southern state of Andhra Pradesh, India. Serum folate and vitamin B12 concentrations were measured by using a competitive radio-binding assay. Digene hybrid capture 2 (HC2) assay results were used to categorize women into two groups, positive or negative for HR-HPVs. Unconditional logistic regression models specified a binary indicator of HC2 (positive/negative) as the dependent variable and serum folate concentrations combined with serum vitamin B12 concentrations as the independent predictor of primary interest. Models were fitted, adjusting for age, education, marital status, parity, type of fuel used for cooking and smoking status. Results: Women with higher concentrations of serum folate (>6 ng/mL) and vitamin B12 (>356 pg/mL) were at lower risk of being positive for HR-HPVs compared to those with serum folate ?6 ng/mL and serum vitamin B12 ? 356 pg/mL (odds ratio = 0.26; 95% confidence interval: 0.08–0.89; P = 0.03). Conclusions: These results demonstrated that improving folate and vitamin B12 status in Indian women may have a beneficial impact on the prevention of CC. Micronutrient based interventions for control of HR-HPV infections may represent feasible alternatives to vaccine based approaches to HPV disease prevention, which are currently unaffordable for use in resource limited areas in rural India.

Piyathilake, Chandrika J; Badiga, Suguna; Paul, Proma; Vijayaraghavan, K; Vedantham, Haripriya; Sudula, Mrudula; Sowjanya, Pavani; Ramakrishna, Gayatri; Shah, Keerti V; Partridge, Edward E; Gravitt, Patti E



Rationale, design and baseline characteristics of a large, simple, randomized trial of combined folic acid and vitamins B6 and B12 in high-risk patients: The Heart Outcomes Prevention Evaluation (HOPE)-2 trial  

PubMed Central

BACKGROUND Epidemiological studies suggest that mild to moderate elevation in plasma homocysteine concentration is associated with increased risk of atherothrombotic cardiovascular (CV) disease. Simple, inexpensive and nontoxic therapy with folic acid and vitamins B6 and B12 reduces plasma homocysteine levels by approximately 25% to 30% and may reduce CV events. Therefore, a large, randomized clinical trial – the Heart Outcomes Prevention Evaluation (HOPE)-2 study – is being conducted to evaluate this therapy in patients at high risk for CV events. OBJECTIVES To evaluate whether long-term therapy with folic acid and vitamins B6 and B12 reduces the risk of major CV events in a high-risk population. The primary study outcome is the composite of death from CV causes, myocardial infarction and stroke. METHODS A total of 5522 patients aged 55 years or older with pre-existing CV disease or with diabetes and additional risk factor(s) at 145 centres in 13 countries were randomly assigned to daily therapy with combined folic acid 2.5 mg, vitamin B6 50 mg and vitamin B12 1 mg, or to placebo. Follow-up will average five years, to be completed by the end of 2005. RESULTS The patients’ baseline characteristics confirmed their high-risk status. Baseline homocysteine levels varied between countries and regions. HOPE-2 is one of the largest trials of folate and vitamins B6 and B12 and is expected to significantly contribute to the evaluation of the role of homocysteine lowering in CV prevention.



Methyl Vitamin B12 but not methylfolate rescues a motor neuron-like cell line from homocysteine-mediated cell death  

SciTech Connect

Homocysteine is an excitatory amino acid implicated in multiple diseases including amyotrophic lateral sclerosis (ALS). Information on the toxicity of homocysteine in motor neurons is limited and few studies have examined how this toxicity can be modulated. In NSC-34D cells (a hybrid cell line derived from motor neuron-neuroblastoma), homocysteine induces apoptotic cell death in the millimolar range with a TC{sub 50} (toxic concentration at which 50% of maximal cell death is achieved) of 2.2 mM, confirmed by activation of caspase 3/7. Induction of apoptosis was independent of short-term reactive oxygen species (ROS) generation. Methyl Vitamin B12 (MeCbl) and methyl tetrahydrofolate (MTHF), used clinically to treat elevated homocysteine levels, were tested for their ability to reverse homocysteine-mediated motor neuron cell death. MeCbl in the micromolar range was able to provide neuroprotection (2 h pretreatment prior to homocysteine) and neurorescue (simultaneous exposure with homocysteine) against millimolar homocysteine with an IC{sub 50} (concentration at which 50% of maximal cell death is inhibited) of 0.6 {mu}M and 0.4 {mu}M, respectively. In contrast, MTHF (up to 10 {mu}M) had no effect on homocysteine-mediated cell death. MeCbl inhibited caspase 3/7 activation by homocysteine in a time- and dose-dependent manner, whereas MTHF had no effect. We conclude that MeCbl is effective against homocysteine-induced cell death in motor neurons in a ROS-independent manner, via a reduction in caspase activation and apoptosis. MeCbl decreases Hcy induced motor neuron death in vitro in a hybrid cell line derived from motor neuron-neuroblastoma and may play a role in the treatment of late stage ALS where HCy levels are increased in animal models of ALS.

Hemendinger, Richelle A., E-mail:; Armstrong, Edward J.; Brooks, Benjamin Rix



A phase I study of pemetrexed (LY231514) supplemented with folate and vitamin B12 in Japanese patients with solid tumours.  


The purpose of this study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of pemetrexed with folate and vitamin B12 supplementation (FA/VB(12)) in Japanese patients with solid tumours and to investigate the safety, efficacy, and pharmacokinetics of pemetrexed. Eligible patients had incurable solid tumours by standard treatments, a performance status 0-2, and adequate organ function. Pemetrexed from 300 to 1,200 mg m(-2) was administered as a 10-min infusion on day 1 of a 21-day cycle with FA/VB(12). Totally, 31 patients were treated. Dose-limiting toxicities were alanine aminotransferase (ALT) elevation at 700 mg m(-2), and infection and skin rash at 1,200 mg m(-2). The MTD/RD were determined to be 1,200/1,000 mg m(-2), respectively. The most common grade 3/4 toxicities were neutropenia (grade (G) 3:29, G4:3%), leucopenia (G3:13, G4:3%), lympopenia (G3:13%) and ALT elevation (G3:13%). Pemetrexed pharmacokinetics in Japanese were not overtly different from those in western patients. Partial response was achieved for 5/23 evaluable patients (four with non-small cell lung cancer (NSCLC) and one with thymoma). The MTD/RD of pemetrexed were determined to be 1,200/1,000 mg m(-2), respectively, that is, a higher RD than without FA/VB(12) (500 mg m(-2)). Pemetrexed with FA/VB(12) showed a tolerable toxicity profile and potent antitumour activity against NSCLC in this study. PMID:16940981

Nakagawa, K; Kudoh, S; Matsui, K; Negoro, S; Yamamoto, N; Latz, J E; Adachi, S; Fukuoka, M



Polymorphism C776G in the transcobalamin II gene and homocysteine, folate and vitamin B12 concentrations. Association with MTHFR C677T and A1298C and MTRR A66G polymorphisms in healthy children.  


One of the etiologies of hyperhomocysteinemia is decreased vitamin B(12). Genetic variation in the transcobalamin II gene, the transporter of vitamin B(12) to the cells, may produce altered homocysteine levels. We determined transcobalamin II C776G polymorphism, homocysteine, folate and vitamin B(12) levels and analyzed the interactive effect with the methylenetetrahydrofolate reductase C677T and A1298C and methionine synthase reductase A66G polymorphisms in 207 healthy Brazilian children. The prevalence of GG genotype of transcobalamin II C776G polymorphism in this Brazilian population, a highly miscigeneous population was 12.5% and the statistical analysis showed that this population is in Hardy-Weinberg equilibrium, it could be considered representative of the general population. We observed a significant increase in homocysteine in the 776GG vs. 776CC genotype, corroborating the influence of age as a determinant of homocysteine in relation to this polymorphism. When we analyzed vitamin B(12) and its relationship with the C776G polymorphism, we found no significant differences. Only 776CG/66AA or 776GG/66AG genotypes presented a significant increase in homocysteine when compared with other groups. In the multivariate analysis, transcobalamin II C776G (CC/CG vs. GG), methylenetetrahydrofolate reductase C677T (CC/CT vs. TT), folate, gender and age presented statistical significance in relation to the homocysteine. These can be considered independent risk factors for hyperhomocysteinemia in this children group. Our results, if confirmed in other populations, highlight the necessity for investigation of the transcobalamin II C776G polymorphism in the research for hyperhomocysteinemia risk factors. PMID:16820193

Aléssio, Ana C M; Höehr, Nelci F; Siqueira, Lúcia H; Bydlowski, Sérgio P; Annichino-Bizzacchi, Joyce M



Dietary intake of the water-soluble vitamins B1, B2, B6, B12 and C in 10 countries in the European Prospective Investigation into Cancer and Nutrition  

Microsoft Academic Search

Objectives:To describe the intake of vitamins thiamine (B1), riboflavin (B2), B6 (pyridoxine), B12 (cobalamine) and C (ascorbic acid) and their food sources among 27 centres in 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Methods:Between 1995 and 2000, 36 034 persons aged between 35 and 74 years were administered a standardized 24-h dietary recall using

A Olsen; J Halkjær; C H van Gils; B Buijsse; H Verhagen; M Jenab; M C Boutron-Ruault; U Ericson; M C Ocké; P H M Peeters; M Touvier; M Niravong; M Waaseth; G Skeie; K T Khaw; R Travis; P Ferrari; M J Sanchez; A Agudo; K Overvad; J Linseisen; C Weikert; C Sacerdote; A Evangelista; D Zylis; K Tsiotas; J Manjer; B van Guelpen; E Riboli; N Slimani; S Bingham



Nucleotide sequence of the btuCED genes involved in vitamin B12 transport in Escherichia coli and homology with components of periplasmic-binding-protein-dependent transport systems.  

PubMed Central

The products of the btuCED region of the Escherichia coli chromosome participate in the transport of vitamin B12 across the cytoplasmic membrane. The nucleotide sequence of the 3,410-base-pair HindIII-HincII DNA fragment carrying a portion of the himA gene and the entire btuCED region was determined. Comparison of the location of the open reading frames with the gene boundaries defined by transposon insertions allowed the assignment of polypeptide products to gene sequences. The btuC product is a highly nonpolar integral membrane protein of molecular weight 31,683. The distribution of hydrophobic regions suggests the presence of numerous membrane-spanning domains. The btuD product is a relatively polar but membrane-associated polypeptide of Mr 27,088 and contains segments bearing extensive homology to the ATP-binding peripheral membrane constituents of periplasmic binding protein-dependent transport systems. Other regions of this protein are similar to portions of the outer membrane vitamin B12 receptor. The btuE product (Mr 20,474) appears to have a periplasmic location. It has the mean hydropathy of a soluble protein but lacks an obvious signal sequence. The cellular locations and structural and sequence homologies of the Btu polypeptides point to the similarity of these three proteins to components of binding protein-dependent transport systems. However, the dependence on a periplasmic vitamin B12-binding protein has not yet been demonstrated.

Friedrich, M J; de Veaux, L C; Kadner, R J



Calcidiol and vitamin D binding protein uptake by LLC-PK/sub 1/ cells  

SciTech Connect

The process by which target cells take up vitamin D and its metabolites is not known. The authors studied the uptake of both /sup 3/H-calcidiol and /sup 125/I-Vitamin D Binding Protein (DBP) by LLC-PK/sub 1/ cells. Uptake was directly related to their extracellular concentrations. In the presence of 55 serum in the growth media cells previously incubated with 10 nM calcitriol for 4 hr had a greater uptake of calcidiol than those cells not incubated with calcitriol. This effect of calcitriol on calcidiol uptake was absent when cells were grown in hormone-supplemented, serum-free media, despite these cells having a cytosolic calcitriol receptor. Equal uptake of calcidiol occurred when DBP was absent and when DBP was present in a one to one molar ratio to calcidiol. With a 1:1 ratio of DBP to calcidiol and a measured K/sub D/ of 2 x 10/sup -8/M, the uptake of calcidiol could not be accounted for by uptake of the free ligand alone. A large excess of DBP (100:1) in relation to calcidiol suppressed uptake of calcidiol by approx. 90%. The authors have not been able to identify a saturable, specific uptake of either calcidiol or DBP despite DBP appearing to facilitate calcidiol uptake.

Keenan, M.J.; Holmes, R.P.



Betaine Stimulation of Vitamin B12 Biosynthesis in Pseudomonas denitrificans May Be Mediated by an Increase in Activity of  -Aminolaevulinic Acid Synthase  

Microsoft Academic Search

~ ~ ~ ~~~~~ ~~ ~~ The stimulation by betaine of vitamin B, and extracellular coproporphyrin production in the industrial species Pseudomonas denitrificuns GY 57\\/2 was confirmed using a replacement culture technique; biosynthesis of haem was also found to be stimulated. In the absence of betaine, 6-aminolaevulinic acid synthase decreased in specific activity from time zero. In the presence of

J. P. Kusel; Y. H. Fa; A. L. Demain



Neurologic aspects of cobalamin (B12) deficiency.  


Optimal functioning of the central and peripheral nervous system is dependent on a constant supply of appropriate nutrients. Particularly important for optimal functioning of the nervous system is cobalamin (vitamin B12). Cobalamin deficiency is particularly common in the elderly and after gastric surgery. Many patients with clinically expressed cobalamin deficiency have intrinsic factor-related malabsorption such as that seen in pernicious anemia. The commonly recognized neurological manifestations of cobalamin deficiency include a myelopathy with or without an associated neuropathy. This review deals with neurological aspects of vitamin B12 deficiency and attempts to highlight recent developments. PMID:24365360

Kumar, Neeraj



Investigations of the mechanism of vitamin E removal from blood and the effect of NO/sub 2/ on the pulmonary uptake of vitamin E  

SciTech Connect

To examine the effect of NO/sub 2/ on vitamin E uptake by lung, we first investigated the mechanism of removal of vitamin E from blood. To accomplish this, a method for labeling serum with tritiated vitamin E was developed. Two other lipids, whose uptake is better understood, were also studied, and compared with vitamin E. Tritiated triacylglycerol was used to monitor lipoprotein lipase-mediated uptake, while tritiated cholesterol was used to monitor LDL receptor-mediated uptake. Blood curves derived from untreated, adult, male, Long-Evans rats indicated that all three lipids were removed biexponentially. The half-life for the Rapid component was 2.5-3.7 minutes for all lipids. The slower curve had half-lives of 42.3 minutes for triacylglycerol, 990.0 minutes for cholesterol, and 288.8 minutes for vitamin E. Biological screening of labeled serum demonstrated that the faster process was not simply the removal of lipoproteins damaged by the labeling process. Hepatectomy affected the rate of neither triacylglycerol nor cholesterol removal, but did slow vitamin E uptake, suggesting a distinct role for liver in vitamin E extraction.

Gardner, H.K.



Point mutations in a conserved region (TonB box) of Escherichia coli outer membrane protein BtuB affect vitamin B12 transport.  

PubMed Central

Uptake of cobalamins and iron chelates in Escherichia coli K-12 is dependent on specific outer membrane transport proteins and the energy-coupling function provided by the TonB protein. The btuB product is the outer membrane receptor for cobalamins, bacteriophage BF23, and the E colicins. A short sequence near the amino terminus of mature BtuB, previously called the TonB box, is conserved in all tonB-dependent receptors and colicins and is the site of the btuB451 mutation (Leu-8----Pro), which prevents energy-coupled cobalamin uptake. This phenotype is partially suppressed by certain mutations in tonB. To examine the role of individual amino acids in the TonB box of BtuB, more than 30 amino acid substitutions in residues 6 to 13 were generated by doped oligonucleotide-directed mutagenesis. Many of the mutations affecting each amino acid did not impair transport activity, although some substitutions reduced cobalamin uptake and the Leu-8----Pro and Val-10----Gly alleles were completely inactive. To test whether the btuB451 mutation affects only cobalamin transport, a hybrid gene was constructed which encodes the signal sequence and first 39 residues of BtuB fused to the bulk of the ferrienterobactin receptor FepA (residues 26 to 723). This hybrid protein conferred all FepA functions but no BtuB functions. The presence of the btuB451 mutation in this fusion gene eliminated all of its tonB-coupled reactions, showing that the TonB box of FepA could be replaced by that from BtuB. These results suggest that the TonB-box region of BtuB is involved in active transport in a manner dependent not on the identity of specific side chains but on the local secondary structure.

Gudmundsdottir, A; Bell, P E; Lundrigan, M D; Bradbeer, C; Kadner, R J



Superoxide-dependent uptake of vitamin C in human glioma cells.  


Glioblastomas are lethal brain tumors that resist current cytostatic therapies. Vitamin C may antagonize the effects of reactive oxygen species (ROS) generating therapies; however, it is often used to reduce therapy-related side effects despite its effects on therapy or tumor growth. Because the mechanisms of vitamin C uptake in gliomas are currently unknown, we evaluated the expression of the sodium-vitamin C cotransporter (SVCT) and facilitative hexose transporter (GLUT) families in human glioma cells. In addition, as microglial cells can greatly infiltrate high-grade gliomas (constituting up to 45% of cells in glioblastomas), the effect of TC620 glioma cell interactions with microglial-like HL60 cells on vitamin C uptake (Bystander effect) was determined. Although glioma cells expressed high levels of the SVCT isoform-2 (SVCT2), low functional activity, intracellular localization and the expression of the dominant-negative isoform (dnSVCT2) were observed. The increased glucose metabolic activity of glioma cells was evident by the high 2-Deoxy-d-glucose and dehydroascorbic acid (DHA) uptake rates through the GLUT isoform-1 (GLUT1), the main DHA transporter in glioblastoma. Co-culture of glioma cells and activated microglial-like HL60 cells resulted in extracellular ascorbic acid oxidation and high DHA uptake by glioma cells. This Bystander effect may explain the high antioxidative potential observed in high-grade gliomas. This study strongly suggests that the Bystander effect, that is, glioma cell interaction with oxidant-producing microglia, could be an important mechanism for glioma vitamin C loading in the absence of functional sodium-vitamin C cotransporter 2 (SVCT2) expression. The high cellular vitamin C load in glioma cells results from a high uptake of extracellular dehydroascorbic acid (DHA) generated by neighboring microglia. This Bystander effect may explain the high antioxidative potential observed in high-grade gliomas, considering that high-grade gliomas may be the only neoplasm where oxidant-producing microglia can almost equal the number of tumor cells. PMID:23859461

Rodríguez, Federico S; Salazar, Katterine A; Jara, Nery A; García-Robles, María A; Pérez, Fernando; Ferrada, Luciano E; Martínez, Fernando; Nualart, Francisco J



The 380 kb pCMU01 plasmid encodes chloromethane utilization genes and redundant genes for vitamin B12- and tetrahydrofolate-dependent chloromethane metabolism in Methylobacterium extorquens CM4: a proteomic and bioinformatics study.  


Chloromethane (CH3Cl) is the most abundant volatile halocarbon in the atmosphere and contributes to the destruction of stratospheric ozone. The only known pathway for bacterial chloromethane utilization (cmu) was characterized in Methylobacterium extorquens CM4, a methylotrophic bacterium able to utilize compounds without carbon-carbon bonds such as methanol and chloromethane as the sole carbon source for growth. Previous work demonstrated that tetrahydrofolate and vitamin B12 are essential cofactors of cmuA- and cmuB-encoded methyltransferases of chloromethane dehalogenase, and that the pathway for chloromethane utilization is distinct from that for methanol. This work reports genomic and proteomic data demonstrating that cognate cmu genes are located on the 380 kb pCMU01 plasmid, which drives the previously defined pathway for tetrahydrofolate-mediated chloromethane dehalogenation. Comparison of complete genome sequences of strain CM4 and that of four other M. extorquens strains unable to grow with chloromethane showed that plasmid pCMU01 harbors unique genes without homologs in the compared genomes (bluB2, btuB, cobA, cbiD), as well as 13 duplicated genes with homologs of chromosome-borne genes involved in vitamin B12-associated biosynthesis and transport, or in tetrahydrofolate-dependent metabolism (folC2). In addition, the presence of both chromosomal and plasmid-borne genes for corrinoid salvaging pathways may ensure corrinoid coenzyme supply in challenging environments. Proteomes of M. extorquens CM4 grown with one-carbon substrates chloromethane and methanol were compared. Of the 49 proteins with differential abundance identified, only five (CmuA, CmuB, PurU, CobH2 and a PaaE-like uncharacterized putative oxidoreductase) are encoded by the pCMU01 plasmid. The mainly chromosome-encoded response to chloromethane involves gene clusters associated with oxidative stress, production of reducing equivalents (PntAA, Nuo complex), conversion of tetrahydrofolate-bound one-carbon units, and central metabolism. The mosaic organization of plasmid pCMU01 and the clustering of genes coding for dehalogenase enzymes and for