Vitamin B6 Effects on one-carbon metabolism
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ABSTRACT:
ORGANISM(S): Homo Sapiens
TISSUE(S): Unspecified
PROVIDER: ST000293 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
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Project description:We experimented with a mathematical model for 1-carbon metabolism and glutathione (GSH) synthesis to investigate the effects of vitamin B-6 deficiency on the reaction velocities and metabolite concentrations in this metabolic network. The mathematical model enabled us to independently alter the activities of each of the 5 vitamin B-6-dependent enzymes and thus determine which inhibitions were responsible for the experimentally observed consequences of a vitamin B-6 deficiency. The effect of vitamin B-6 deficiency on serine and glycine concentrations in tissues and plasma was almost entirely due to its effects on the activity of glycine decarboxylase. The effect of vitamin B-6 restriction on GSH concentrations appeared to be indirect, arising from the fact that vitamin B-6 restriction increases oxidative stress, which, in turn, affects several enzymes in 1-carbon metabolism as well as the GSH transporter. Vitamin B-6 restriction causes an abnormally high and prolonged homocysteine response to a methionine load test. This effect appeared to be mediated solely by its effects on cystathionine beta-synthase. Reduction of the enzymatic activity of serine hydroxymethyltransferase (SHMT) had negligible effects on most metabolite concentrations and reaction velocities. Reduction or total elimination of cytoplasmic SHMT had a surprisingly moderate effect on metabolite concentrations and reaction velocities. This corresponds to the experimental findings that a reduction in the enzymatic activity of SHMT has little effect on 1-carbon metabolism. Our simulations showed that the primary function of SHMT was to increase the rate by which the glycine-serine balance was reequilibrated after a perturbation.
| S-EPMC2666368 | biostudies-literature
Project description:Vitamin D (vitD) deficiency (25-hydroxy-vitamin D < 50 nmol/L) is common in pregnancy and associated with an increased risk of adverse pregnancy outcomes. High-dose vitD supplementation is suggested to improve pregnancy health, but there is limited knowledge about the effects on placental vitD transport and metabolism and the vitD status of newborns. Comparing the current standard maternal supplementation, 10 µg/day to a 90 µg vitD supplement, we investigated placental gene expression, maternal vitD transport and neonatal vitD status. Biological material was obtained from pregnant women randomized to 10 µg or 90 µg vitD supplements from week 11-16 onwards. Possible associations between maternal exposure, neonatal vitD status and placental expression of the vitD receptor (VDR), the transporters (Cubilin, CUBN and Megalin, LRP2) and the vitD-activating and -degrading enzymes (CYP24A1, CYP27B1) were investigated. Maternal vitD-binding protein (VDBP) was determined before and after supplementation. Overall, 51% of neonates in the 10 µg vitD group were vitD-deficient in contrast to 11% in the 90 µg group. High-dose vitD supplementation did not significantly affect VDBP or placental gene expression. However, the descriptive analyses indicate that maternal obesity may lead to the differential expression of CUBN, CYP24A1 and CYP27B1 and a changed VDBP response. High-dose vitD improves neonatal vitD status without affecting placental vitD regulation.
| S-EPMC11243372 | biostudies-literature
Project description:Oleanolic acid (OA) is a triterpenoid with reported bone anti-resorption activities. The present study aimed to characterize its bone protective effects in vivo and to study its effects on vitamin D metabolism, both in vivo and in vitro. OA significantly increased bone mineral density, improved micro-architectural properties, reduced urinary Ca excretion, increased 1,25(OH)₂D₃ and renal CYP27B1 mRNA expression in mature C57BL/6 ovariectomised (OVX) mice. OA also improved bone properties, Ca balance, and exerted modulatory effects on renal CYP27B1 and CYP24A1 expressions in aged normal female Sprague-Dawley rats. In addition, OA significantly increased renal CYP27B1 mRNA and promoter activity, and suppressed CYP24A1 mRNA and protein expressions in human proximal tubule HKC-8 cells. OA exerted bone protective effects in mature OVX mice and aged female rats. This action on bone might be, at least in part, associated with its effects on Ca and vitamin D metabolism. The present findings suggest that OA is a potential drug candidate for the management of postmenopausal osteoporosis.
| S-EPMC5852823 | biostudies-literature
Project description:1,25-Dihydroxvitamin D3 [1,25(OH)2D3] is the hormonally active form of vitamin D. The genomic mechanism of 1,25(OH)2D3 action involves the direct binding of the 1,25(OH)2D3 activated vitamin D receptor/retinoic X receptor (VDR/RXR) heterodimeric complex to specific DNA sequences. Numerous VDR co-regulatory proteins have been identified, and genome-wide studies have shown that the actions of 1,25(OH)2D3 involve regulation of gene activity at a range of locations many kilobases from the transcription start site. The structure of the liganded VDR/RXR complex was recently characterized using cryoelectron microscopy, X-ray scattering, and hydrogen deuterium exchange. These recent technological advances will result in a more complete understanding of VDR coactivator interactions, thus facilitating cell and gene specific clinical applications. Although the identification of mechanisms mediating VDR-regulated transcription has been one focus of recent research in the field, other topics of fundamental importance include the identification and functional significance of proteins involved in the metabolism of vitamin D. CYP2R1 has been identified as the most important 25-hydroxylase, and a critical role for CYP24A1 in humans was noted in studies showing that inactivating mutations in CYP24A1 are a probable cause of idiopathic infantile hypercalcemia. In addition, studies using knockout and transgenic mice have provided new insight on the physiological role of vitamin D in classical target tissues as well as evidence of extraskeletal effects of 1,25(OH)2D3 including inhibition of cancer progression, effects on the cardiovascular system, and immunomodulatory effects in certain autoimmune diseases. Some of the mechanistic findings in mouse models have also been observed in humans. The identification of similar pathways in humans could lead to the development of new therapies to prevent and treat disease.
| S-EPMC4839493 | biostudies-literature
Project description:ContextVitamin D2 and vitamin D3 have been hypothesized to exert differential effects on vitamin D metabolism.ObjectiveTo compare the influence of administering vitamin D2 vs vitamin D3 on metabolism of vitamin D3.MethodsWe measured baseline and 4-month serum concentrations of vitamin D3, 25-hydroxyvitamin D3 [25(OH)D3], 25-hydroxyvitamin D2, 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3], 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], and 4β,25-dihydroxyvitamin D3 [4β,25(OH)2D3] in 52 adults randomized to receive a total of four oral bolus doses of 2.5 mg vitamin D2 (n = 28) or vitamin D3 (n = 24) over four months. Metabolite-to-parent compound ratios were calculated to estimate hydroxylase activity. Pairwise before vs after comparisons were made to evaluate effects of vitamin D2 and vitamin D3 on metabolism of vitamin D. Mean postsupplementation metabolite-to-parent ratios were then compared between groups.ResultsVitamin D2 was less effective than vitamin D3 in elevating total serum 25(OH)D concentration. Vitamin D2 suppressed mean four-month serum concentrations of 25(OH)D3, 24R,25(OH)2D3, 1α,25(OH)2D3, and 4β,25(OH)2D3 and mean ratios of 25(OH)D3 to D3 and 1α,25(OH)2D3 to 25(OH)D3, while increasing the mean ratio of 24R,25(OH)2D3 to 25(OH)D3. Vitamin D3 increased mean four-month serum concentrations of 25(OH)D3, 24R,25(OH)2D3, 1α,25(OH)2D3, and 4β,25(OH)2D3 and the mean ratio of 24R,25(OH)2D3 to 25(OH)D3. Participants receiving vitamin D2 had lower mean postsupplementation ratios of 25(OH)D3 to vitamin D3 and 1α,25(OH)2D3 to 25(OH)D3 than those receiving vitamin D3. Mean postsupplementation ratios of 24R,25(OH)2D3 to 25(OH)D3 and 4β,25(OH)2D3 to 25(OH)D3 did not differ between groups.ConclusionsBolus-dose vitamin D2 is less effective than bolus-dose vitamin D3 in elevating total serum 25(OH)D concentration. Administration of vitamin D2 reduces 25-hydroxylation of vitamin D3 and 1-α hydroxylation of 25(OH)D3, while increasing 24R-hydroxylation of 25(OH)D3.
| S-EPMC6797055 | biostudies-literature
Project description:Vitamin B12 is an essential nutritional co-factor for the folate and methionine cycles, which together constitute one-carbon metabolism. Here, we show that dietary uptake of vitamin B12 modulates cell fate decisions controlled by the conserved RAS/MAPK signaling pathway in C. elegans. A bacterial diet rich in vitamin B12 increases vulval induction, germ cell apoptosis and oocyte differentiation. These effects are mediated by different one-carbon metabolites in a tissue-specific manner. Vitamin B12 enhances via the choline/phosphatidylcholine metabolism vulval induction by down-regulating fat biosynthesis genes and increasing H3K4 tri-methylation, which results in increased expression of RAS/MAPK target genes. Furthermore, the nucleoside metabolism and H3K4 tri-methylation positively regulate germ cell apoptosis and oocyte production. Using mammalian cells carrying different activated KRAS and BRAF alleles, we show that the effects of methionine on RAS/MAPK-regulated phenotype are conserved in mammals. Our findings suggest that the vitamin B12-dependent one-carbon metabolism is a limiting factor for diverse RAS/MAPK-induced cellular responses.
| S-EPMC11408588 | biostudies-literature
Project description:Vitamin B-6, folate and homocysteine may play a critical role in the colorectal cancer progression. This is a 4-y study and the specific aims are: 1) to compare vitamin B-6, folate and homocysteine status, oxidative stress, antioxidant activities and DNA methylation between subjects with colorectal polyps and colorectal cancer; 2) to study the effects of vitamin B-6, folate and homocysteine status on oxidative stress, antioxidant activities and DNA methylation in colorectal cancer patients; 3) to evaluate whether folic acid and/or pyridoxine supplementation had a beneficial effect on oxidative stress, antioxidant activities and DNA methylation in patients with colorectal; 4) to compare vitamin B-6, folate and homocysteine status, oxidative stress, antioxidant activities and DNA methylation between colorectal cancer patients and age-, sex-matched healthy subjects; 5) to evaluate the effect of vitamin B-6, folate and homocysteine status, oxidative stress, antioxidant activities and DNA methylation on the risk of colorectal cancer (odds ratio); 6) to follow the effects of vitamin B-6, folate and homocysteine status, oxidative stress, antioxidant activities and DNA methylation on the occurrence of colorectal cancer; 7) to follow the effects of pyridoxine and/or folic acid supplementation on the occurrence of colorectal cancer.
This protocol is designed as a hospital-based cross-sectional, case-control, double blinded randomized placebo-controlled intervention and follow-up trial. Three hundred colorectal cancer patients and 300 age-, sex-matched controls who meet the inclusion criteria will be recruited from Taichung General Veterans Hospital. If cancer patients’ plasma pyridoxal 5’-phosphate (PLP) level less than 30 nmol/L will be asked to participate the intervention study and will be blinded and randomly assigned to either the 1) control (vitamin C, 100 mg/d); 2) 50 mg vitamin B-6; 3) 400 microgram/d folic acid; or 4) vitamin B-6 (50 mg/d) plus folic acid (400 microgram/d) for 1 year. Data on demography, anthropometry, medical history, food frequency questionnaire and 24-h diet recall will be collected. Cancer patients will have fasting blood drawn before surgery or receiving chemotherapy. Additionally, fasting blood samples will be obtained at month 0, 3, 6, 9 and 12 during intervention period and at month 6, 12, 18, 24, 30, 36, 42 and 48 during follow-up. Hematological, plasma and erythrocyte PLP, plasma pyridoxal and 4-pyridoxic acid, serum and erythrocyte folate, serum vitamin B-12, homocysteine, SAM, SAH, lipid peroxidation indicators (TBARS, oxidized LDL), glutathione, antioxidant enzymatic activities and DNA methylation and MTHFR 677C>T polymorphism will be measured.
| 2112226 | ecrin-mdr-crc
Project description:Necrotic enteritis (NE) is an important enteric inflammatory disease of poultry, and the effects of vitamin A (VitA) on NE birds are largely unknown. The present study was conducted to investigate the effects of VitA on the immune responses and VitA metabolism of NE broilers as well as the underlying mechanisms. Using a 2 × 2 factorial arrangement, 336 1-day-old Ross 308 broiler chicks were randomly assigned to 4 groups with 7 replicates. Broilers in the control (Ctrl) group were fed a basal diet without extra VitA supplementation. Broilers in the VitA group were fed a basal diet supplemented with 12,000 IU/kg of VitA. Birds in NE and VitA + NE groups were fed corresponding diets and, in addition, co-infected with Eimeria spp. and Clostridium perfringens on days 14 to 20. Samples of the blood, jejunum, spleen and liver were obtained on day 28 for analysis, and meanwhile, lesion scores were also recorded. The results showed that NE challenge increased lesion score in the jejunum and decreased serum glucose, total glyceride, calcium, phosphorus and uric acid levels (p < 0.05). VitA supplementation reduced the levels of serum phosphorus, uric acid and alkaline phosphatase in NE-challenged birds and increased serum low-density lipoprotein content and the activity of aspartate aminotransferase and creatine kinase (p < 0.05). Compared with the Ctrl group, the VitA and NE groups had higher mRNA expression of interferon-γ in the jejunum (p < 0.05). NE challenge up-regulated mRNA expression of interleukin (IL)-13, transforming growth factor-β4, aldehyde dehydrogenase (RALDH)-2 and RALDH-3 in the jejunum, while VitA supplementation increased jejunal IL-13 mRNA expression and hepatic VitA content, but down-regulated splenic IL-13 mRNA expression (p < 0.05). The VitA + NE group had higher serum prostaglandin E2 levels and the Ctrl group had higher splenic RALDH-3 mRNA expression than that of the other three groups (p < 0.05). NE challenge up-regulated jejunal retinoic acid receptor (RAR)-β and retinoid X receptor (RXR)-α as well as splenic RAR-α and RAR-β mRNA expression (p < 0.05). VitA supplementation up-regulated jejunal RAR-β expression but down-regulated mRNA expression of RXR-α, RXR-γ, signal transducers and activators of transcription (STAT) 5 and STAT6 in the spleen (p < 0.05). Moreover, compared with the Ctrl group, the VitA and NE groups had down-regulated mRNA expression of jejunal and splenic Janus kinase (JAK) 1 (p < 0.05). In conclusion, NE challenge induced jejunal injury and expression of Th2 and Treg cell-related cytokines and enhanced RALDH and RAR/RXR mRNA expression, mainly in the jejunum of broilers. VitA supplementation did not alleviate jejunal injury or Th2 cell-related cytokine expression; however, it improved hepatic VitA deposition and inhibited the expression of RALDH-3, RXR and the JAK/STAT signaling pathway in the spleen of broilers. In short, the present study suggested the modulatory effects of vitamin A on the immune responses and vitamin A metabolism in broiler chickens challenged with necrotic enteritis.
| S-EPMC10221067 | biostudies-literature
Project description:Observational studies with healthy persons demonstrated an inverse association of vitamin E with the risk of coronary heart disease or cancer, the outcome of large-scale clinical trials conducted to prove a benefit of vitamin E in the recurrence and/or progression of such disease, however, was disappointing. Vitamin E did not provide benefits to patients with cardiovascular diseases, cancer, diabetes or hypertension. Even harmful events and worsening of pre-existing diseases were reported, which are hard to explain. Since vitamin E is metabolized along the same routes as xenobiotics and induces drug-metabolizing enzymes in rodents, it is hypothesized that a supplementation with high dosages of vitamin E may also lead to an induction of the drug-metabolizing system in patients that depend on drug therapy. Compromising essential therapy might therefore outweigh any benefit of vitamin E in patients. It is recommended to work out at which threshold the drug-metabolizing system can be induced in humans before new trials with high dosages of vitamin E are started.
| S-EPMC2474942 | biostudies-other
Project description:In humans, most free tryptophan is degraded via kynurenine pathways into kynurenines. Kynurenines modulate the immune system, central nervous system, and skeletal muscle bioenergetics. Consequently, kynurenine pathway metabolites (KPMs) have been studied in the context of exercise. However, the effect of vitamin D supplementation on exercise-induced changes in KPMs has not been investigated. Here, we analyzed the effect of a single high-dose vitamin D supplementation on KPMs and tryptophan levels in runners after an ultramarathon. In the study, 35 amateur runners were assigned into two groups: vitamin D supplementation group, administered 150,000 IU vitamin D in vegetable oil 24 h before the run (n = 16); and control (placebo) group (n = 19). Blood was collected for analysis 24 h before, immediately after, and 24 h after the run. Kynurenic, xanthurenic, quinolinic, and picolinic acids levels were significantly increased after the run in the control group, but the effect was blunted by vitamin D supplementation. Conversely, the decrease in serum tryptophan, tyrosine, and phenylalanine levels immediately after the run was more pronounced in the supplemented group than in the control. The 3-hydroxy-l-kynurenine levels were significantly increased in both groups after the run. We conclude that vitamin D supplementation affects ultramarathon-induced changes in tryptophan metabolism.
| S-EPMC9655671 | biostudies-literature