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The Journal of Clinical Endocrinology... Sep 2022There is little evidence regarding the association between serum vitamin B6 status and catabolism and all-cause mortality in patients with type-2 diabetes mellitus...
CONTEXT
There is little evidence regarding the association between serum vitamin B6 status and catabolism and all-cause mortality in patients with type-2 diabetes mellitus (T2DM).
OBJECTIVE
We aimed to ascertain if the serum level of vitamin B6 and catabolism, including pyridoxal 5'-phosphate (PLP) and 4-pyridoxic acid (4-PA), were associated with risk of all-cause mortality in T2DM patients.
METHODS
This prospective cohort study involved 2574 patients with T2DM who participated in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. The serum concentrations of PLP and 4-PA were used to assess the serum level of vitamin B6. Mortality status was determined by routine follow-up using the National Death Index through December 31, 2015.
RESULTS
Over a median follow-up of 85 months, there were 588 deaths. The fully adjusted Cox model indicated that the highest serum PLP concentrations (> 63.6 nmol/L) were associated with a decrease in all-cause mortality (hazard ratio [HR], 0.74; 95% CI, 0.55-0.99, P trend = .035). The risk for all-cause mortality was 59% higher for participants with the highest quartile of 4-PA level compared with the lowest quartile (HR, 1.62; 95% CI, 1.12-2.35; P trend = .003). The sensitivity and specificity of the combination of PLP and 4-PA levels for the prediction of all-cause mortality were 59.5% and 60.9%, respectively (area under the receiver operating characteristic curve = 0.632). The Kaplan-Meier method was used to estimate overall survival for patients based on different combinations of PLP level and 4-PA level. Patients with PLP less than 24.3 nmol/L and 4-PA greater than or equal to 25.4 nmol/L had the worst outcomes (log-rank P < .001).
CONCLUSION
Overall, our data suggest that a low serum level of PLP and high serum level of 4-PA, which represent the serum level of vitamin B6, increases the risk of all-cause mortality significantly in patients with T2DM.
Topics: Diabetes Mellitus, Type 2; Humans; Nutrition Surveys; Phosphates; Prospective Studies; Pyridoxal Phosphate; Pyridoxic Acid; Vitamin B 6
PubMed: 35907182
DOI: 10.1210/clinem/dgac429 -
The American Journal of Clinical... Aug 2014
Topics: Female; Humans; Male; Vitamin B 6
PubMed: 24990424
DOI: 10.3945/ajcn.114.092445 -
BMJ Case Reports Mar 2020A 73-year-old woman was admitted to the intensive care unit following vomiting and diarrhoea onset after completing oral bowel preparation prior to colonoscopy to...
A 73-year-old woman was admitted to the intensive care unit following vomiting and diarrhoea onset after completing oral bowel preparation prior to colonoscopy to investigate haematochezia. She had a history of severe chronic obstructive pulmonary disease, Crohn's disease, diverticular disease, hypertension and dyslipidaemia. She was resuscitated with intravenous fluids, antibiotics and required epinephrine, norepinephrine and vasopressin infusions. She improved over her 4-day intensive care admission and was discharged to the general medical ward, but ultimately died 19 days after presentation.
Topics: Aged; Cathartics; Citrates; Colonoscopy; Fatal Outcome; Female; Humans; Organometallic Compounds; Picolines; Preoperative Care; Risk Factors; Shock, Septic
PubMed: 32161080
DOI: 10.1136/bcr-2019-233406 -
Nursing Open Jul 2022The aim of this study was to examine the relationship between intake of vitamins B1, B6, B9 and B12 with emotional mental disorders among nurses in Indonesia.
AIM
The aim of this study was to examine the relationship between intake of vitamins B1, B6, B9 and B12 with emotional mental disorders among nurses in Indonesia.
DESIGN
This cross-sectional study included nurses who have worked at least six months at a private hospital in Indonesia from March to April 2021.
METHODS
We used the Food Frequency Questionnaire, Self-Reporting Questionnaire 20 and the Expanded Nursing Stress Scale questionnaire to assess the B-vitamin intake, emotional mental disorders and work-related stress.
RESULTS
Of 80 interviewed nurses, 8.8% experienced severe work-related stress, and 22.5% had emotional mental disorders. Most nurses had inadequate intake of vitamins B1 and B9 but had adequate intake of vitamins B6 (72.5%) and B12 (56.3%). Emotional mental disorders are more probably to occur in nurses with less intake of vitamins B6 and B12, with respective aOR of 20.06, 95% CI 4.14-97.09 (p < .001) and 4.49, 95% CI 1.19-16.83 (p = .026).
Topics: Cross-Sectional Studies; Humans; Indonesia; Mental Disorders; Occupational Stress; Pyridoxine; Thiamine; Vitamin B 12; Vitamin B 6; Vitamin B Complex
PubMed: 35434916
DOI: 10.1002/nop2.1213 -
Biochimica Et Biophysica Acta. General... Jun 2019Pyridoxal 5'-phosphate (PLP) is the active form of vitamin B6. Mammals cannot synthesize vitamin B6, so they rely on dietary uptake of the different B6 forms, and via...
BACKGROUND
Pyridoxal 5'-phosphate (PLP) is the active form of vitamin B6. Mammals cannot synthesize vitamin B6, so they rely on dietary uptake of the different B6 forms, and via the B6 salvage pathway they interconvert them into PLP. Humans possess three enzymes in this pathway: pyridoxal kinase, pyridox(am)ine phosphate oxidase and pyridoxal phosphatase. Besides these, a fourth enzyme has been described in plants and yeast but not in humans: pyridoxal reductase.
METHODS
We analysed B6 vitamers in remnant CSF samples of PLP-treated patients and four mammalian cell lines (HepG2, Caco2, HEK293 and Neuro-2a) supplemented with PL as the sole source of vitamin B6.
RESULTS
Strong accumulation of pyridoxine (PN) in CSF of PLP-treated patients was observed, suggesting the existence of a PN-forming enzyme. Our in vitro studies show that all cell lines reduce PL to PN in a time- and dose-dependent manner. We compared the amino acid sequences of known PL reductases to human sequences and found high homology for members of the voltage-gated potassium channel beta subunits and the human aldose reductases. Pharmacological inhibition and knockout of these proteins show that none of the candidates is solely responsible for PL reduction to PN.
CONCLUSIONS
We show evidence for the presence of PL reductase activity in humans. Further studies are needed to identify the responsible protein.
GENERAL SIGNIFICANCE
This study expands the number of enzymes with a role in B6 salvage pathway. We hypothesize a protective role of PL reductase(s) by limiting the intracellular amount of free PL and PLP.
Topics: Alcohol Oxidoreductases; Caco-2 Cells; HEK293 Cells; Hep G2 Cells; Humans; Pyridoxine; Vitamin B 6
PubMed: 30928491
DOI: 10.1016/j.bbagen.2019.03.019 -
Clinical Nutrition (Edinburgh, Scotland) Jul 2021Vitamin B6 is involved in a large spectrum of physiological processes and comprises of the vitamers pyridoxamine (PM), pyridoxal (PL), pyridoxine (PN), and their... (Clinical Trial)
Clinical Trial
BACKGROUND AND AIMS
Vitamin B6 is involved in a large spectrum of physiological processes and comprises of the vitamers pyridoxamine (PM), pyridoxal (PL), pyridoxine (PN), and their phosphorylated derivatives including the biological active pyridoxal 5'-phosphate (PLP). While PN toxicity is known to complicate several treatments, PM has shown promise in relation to the treatment of metabolic and age-related diseases by blocking oxidative degradation and scavenging toxic dicarbonyl compounds and reactive oxygen species. We aimed to assess the metabolization of oral PM supplements in a single and three daily dose.
MATERIALS AND METHODS
We optimized and validated a method for the quantification of the B6 vitamers in plasma and urine using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Five healthy volunteers were recruited to study PM metabolization after a single oral dose of 200 mg PM or a three daily dose of 67 mg PM. A third protocol was implemented as control for dietary intake. Venous blood samples, 24 h urine and fasted second void urine samples were collected.
RESULTS
After a single oral dose of 200 mg PM, plasma PM increased in the first 3 h to a maximum of 2324 ± 266 nmol/L. While plasma PM levels returned to baseline after ~10 h of PM intake, PLP increased to a maximum of 2787 ± 329 nmol/L and reached a plateau. We found a small increase of PN to a maximum of 13.5 ± 2.1 nmol/L; it was nearly undetectable after ~12 h. With a three daily dose of 67 mg PM we observed an increase and decline of plasma PM, PL, and PN concentrations after each PM intake. PLP showed a similar increase as in the single dose protocol and accumulated over time.
CONCLUSION
In this study we showed high plasma levels of PM after oral PM supplementation. We found steadily increasing levels of the biologically active PLP, with minimal formation of PN. The B6 vitamer PM is an interesting supplement as an inhibitor of harmful processes in metabolic diseases and for the treatment of vitamin B6 deficiency.
CLINICAL TRIAL REGISTRY
The study was approved by the Medical Ethics Committee of Maastricht University (NL) and was registered at ClinicalTrials.gov as NCT02954588.
Topics: Adult; Chromatography, High Pressure Liquid; Dietary Supplements; Female; Healthy Volunteers; Humans; Male; Pyridoxal Phosphate; Pyridoxamine; Pyridoxine; Tandem Mass Spectrometry; Vitamin B 6; Vitamin B 6 Deficiency
PubMed: 34229268
DOI: 10.1016/j.clnu.2021.05.028 -
International Journal of Molecular... Dec 2022Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, serves as a cofactor for scores of B6-dependent (PLP-dependent) enzymes involved in many cellular processes....
Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, serves as a cofactor for scores of B6-dependent (PLP-dependent) enzymes involved in many cellular processes. One such B6 enzyme is dopa decarboxylase (DDC), which is required for the biosynthesis of key neurotransmitters, e.g., dopamine and serotonin. PLP-dependent enzymes are biosynthesized as apo-B6 enzymes and then converted to the catalytically active holo-B6 enzymes by Schiff base formation between the aldehyde of PLP and an active site lysine of the protein. In eukaryotes, PLP is made available to the B6 enzymes through the activity of the B6-salvage enzymes, pyridoxine 5'-phosphate oxidase (PNPO) and pyridoxal kinase (PLK). To minimize toxicity, the cell keeps the content of free PLP (unbound) very low through dephosphorylation and PLP feedback inhibition of PNPO and PLK. This has led to a proposed mechanism of complex formation between the B6-salvage enzymes and apo-B6 enzymes prior to the transfer of PLP, although such complexes are yet to be characterized at the atomic level, presumably due to their transient nature. A computational study, for the first time, was used to predict a likely PNPO and DDC complex, which suggested contact between the allosteric PLP tight-binding site on PNPO and the active site of DDC. Using isothermal calorimetry and/or surface plasmon resonance, we also show that PNPO binds both apoDDC and holoDDC with dissociation constants of 0.93 ± 0.07 μM and 2.59 ± 0.11 μM, respectively. Finally, in the presence of apoDDC, the tightly bound PLP on PNPO is transferred to apoDDC, resulting in the formation of about 35% holoDDC.
Topics: Pyridoxine; Pyridoxaminephosphate Oxidase; Dopa Decarboxylase; Pyridoxal Phosphate; Oxidoreductases; Pyridoxal Kinase
PubMed: 36614085
DOI: 10.3390/ijms24010642 -
Molecular Plant May 2022Despite serving as a major inorganic nitrogen source for plants, ammonium causes toxicity at elevated concentrations, inhibiting root elongation early on. While previous...
Despite serving as a major inorganic nitrogen source for plants, ammonium causes toxicity at elevated concentrations, inhibiting root elongation early on. While previous studies have shown that ammonium-inhibited root development relates to ammonium uptake and formation of reactive oxygen species (ROS) in roots, it remains unclear about the mechanisms underlying the repression of root growth and how plants cope with this inhibitory effect of ammonium. In this study, we demonstrate that ammonium-induced apoplastic acidification co-localizes with Fe precipitation and hydrogen peroxide (HO) accumulation along the stele of the elongation and differentiation zone in root tips, indicating Fe-dependent ROS formation. By screening ammonium sensitivity in T-DNA insertion lines of ammonium-responsive genes, we identified PDX1.1, which is upregulated by ammonium in the root stele and whose product catalyzes de novo biosynthesis of vitamin B. Root growth of pdx1.1 mutants is hypersensitive to ammonium, while chemical complementation or overexpression of PDX1.1 restores root elongation. This salvage strategy requires non-phosphorylated forms of vitamin B that are able to quench ROS and rescue root growth from ammonium inhibition. Collectively, these results suggest that PDX1.1-mediated synthesis of non-phosphorylated B vitamers acts as a primary strategy to protect roots from ammonium-dependent ROS formation.
Topics: Ammonium Compounds; Arabidopsis; Arabidopsis Proteins; Hydrogen Peroxide; Oxidative Stress; Plant Roots; Reactive Oxygen Species; Vitamin B 6; Vitamins
PubMed: 35063660
DOI: 10.1016/j.molp.2022.01.012 -
Organic Letters Jul 2021Hydroperoxides were synthesized in one step from various alkenes using Co(pic) as the catalyst with molecular oxygen and tetramethyldisiloxane (TMDSO). The hydration...
Hydroperoxides were synthesized in one step from various alkenes using Co(pic) as the catalyst with molecular oxygen and tetramethyldisiloxane (TMDSO). The hydration product could be obtained using a modified catalyst, Co(3-mepic), with molecular oxygen and phenylsilane. Formation of hydroperoxides occurred through a rapid Co-O bond metathesis of a peroxycobalt compound with isopropanol.
Topics: Alkenes; Catalysis; Cobalt; Molecular Structure; Picolinic Acids
PubMed: 34125543
DOI: 10.1021/acs.orglett.1c01489 -
Clinical Chemistry and Laboratory... Mar 2013Although vitamin B6 and its metabolite, pyridoxal 5'-phosphate (PLP), have been shown to exert beneficial effects in ischemic heart disease, the mechanisms of their... (Review)
Review
Although vitamin B6 and its metabolite, pyridoxal 5'-phosphate (PLP), have been shown to exert beneficial effects in ischemic heart disease, the mechanisms of their action are not fully understood. Some studies have shown that ventricular arrhythmias and mortality upon the occlusion of coronary artery were attenuated by pretreatment of animals with PLP. Furthermore, ischemia-reperfusion-induced abnormalities in cardiac performance and defects in sarcoplasmic reticular Ca2+-transport activities were decreased by PLP. The increase in cardiac contractile activity of isolated heart by ATP was reduced by PLP, unlike propranolol, whereas that by isoproterenol was not depressed by PLP. ATP-induced increase in [Ca2+]i, unlike KCl-induced increase in [Ca2+]i in cardiomyocytes was depressed by PLP. Both high- and low-affinity sites for ATP binding in sarcolemmal membranes were also decreased by PLP. These observations support the view that PLP may produce cardioprotective effects in ischemic heart disease by attenuating the occurrence of intracellular Ca2+ overload due to the blockade of purinergic receptors.
Topics: Animals; Cardiotonic Agents; Heart; Myocardial Ischemia; Pyridoxal Phosphate; Reperfusion Injury; Vitamin B 6; Vitamin B 6 Deficiency
PubMed: 23314545
DOI: 10.1515/cclm-2012-0553