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Clinica Chimica Acta; International... Sep 2017We quantified pyridoxal 5'-phosphate (PLP), pyridoxal (PL), and 4-pyridoxic acid (PA) in paired serum and cerebrospinal fluid (CSF) samples from children and...
BACKGROUND
We quantified pyridoxal 5'-phosphate (PLP), pyridoxal (PL), and 4-pyridoxic acid (PA) in paired serum and cerebrospinal fluid (CSF) samples from children and investigated the effect of age on the concentrations and CSF-to-serum ratios of these vitamers.
METHODS
Serum and CSF samples prospectively collected from 49 pediatric patients were analyzed. PLP, PL, and PA were measured using high-performance liquid chromatography with fluorescence detection, using pre-column derivatization by semicarbazide. Effects of age on these vitamers, the PLP-to-PL ratio, CSF-to-serum PLP ratio, and CSF-to-serum PL ratio were evaluated using correlation analysis.
RESULTS
The PLP, PL, and PA concentrations in the serum and CSF were higher at younger ages, except for CSF PA concentrations that were mostly below the limit of detection (<1.2nmol/l). The PLP-to-PL ratios in the serum and CSF correlated positively with age. The CSF-to-serum PLP ratio and CSF-to-serum PL ratio were independent of age.
CONCLUSIONS
Age-related changes in PLP, PL, and PA in serum and in CSF from pediatric patients and CSF-to-serum ratios of PLP and PL demonstrated in this study will provide valuable information for evaluating PLP supply to the central nervous system from the peripheral blood.
Topics: Adolescent; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Pyridoxal; Pyridoxal Phosphate; Pyridoxic Acid
PubMed: 28778380
DOI: 10.1016/j.cca.2017.07.032 -
The Cochrane Database of Systematic... Apr 2015Tardive dyskinesia is a chronic and disabling abnormal movement disorder affecting the muscles of the face, neck, tongue and the limbs. It is a common side effect of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tardive dyskinesia is a chronic and disabling abnormal movement disorder affecting the muscles of the face, neck, tongue and the limbs. It is a common side effect of long-term antipsychotic medication use in individuals with schizophrenia and other related psychotic disorders. While there are no known effective treatments for tardive dyskinesia to date, some reports suggest that pyridoxal 5 phosphate may be effective in reducing the severity of tardive dyskinesia symptoms.
OBJECTIVES
To determine the effectiveness of pyridoxal 5 phosphate (vitamin B6 or Pyridoxine or Pyridoxal phosphate) in the treatment of neuroleptic-induced tardive dyskinesia among people with schizophrenia and other related psychotic disorders.
SEARCH METHODS
The Cochrane schizophrenia group's register of clinical trials was searched (January 2013) using the phrase: [*Pyridoxal* OR *Pyridoxine* OR *P5P* OR *PLP* OR *tardoxal* OR *Vitamin B6* O *Vitamin B 6* R in title, abstract or index terms of REFERENCE, or interventions of STUDY. References of relevant identified studies were handsearched and where necessary, the first authors of relevant studies were contacted.
SELECTION CRITERIA
Studies described as randomised controlled trials comparing the effectiveness pyridoxal 5 phosphate with placebo in the treatment of neuroleptic-induced tardive dyskinesia among patients with schizophrenia.
DATA COLLECTION AND ANALYSIS
The review authors independently extracted data from each selected study. For dichotomous data, we calculated risk ratios (RR) and their 95% confidence intervals (CIs) on an intention-to-treat basis based on a fixed-effect model. For continuous data, we calculated mean differences (MD) with 95% CIs, again based on a fixed-effect model. We assessed risk of bias for each included study and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to rate quality of evidence.
MAIN RESULTS
Of the 12 records retrieved by the search, three trials published in 2001, 2003 and 2007, involving 80 inpatients with schizophrenia, aged 18 to 71 years, admitted in a psychiatric facility and followed up for a period nine weeks to 26 weeks, were included. Overall, pyridoxal 5 phosphate produced a significant improvement in tardive dyskinesia symptoms when compared with placebo, assessed by a change in Extrapyramidal Symptoms Rating Scale (ESRS) scores from baseline to the end of the first phase of the included studies (2 RCTs n = 65, RR 19.97, CI 2.87 to 139.19, low quality evidence). The endpoint tardive dyskinesia score (a measure of its severity) assessed with the ESRS, was significantly lower among participants on pyridoxal 5 phosphate compared to those on placebo (2 RCTs n = 60, MD -4.07, CI -6.36 to -1.79, low quality evidence).It was unclear whether pyridoxal 5 phosphate led to more side effects (n = 65, 2 RCTs, RR 3.97, CI 0.20 to 78.59, low quality evidence) or caused deterioration in tardive dyskinesia symptoms when compared to placebo (n = 65, 2 RCTs, RR 0.16, CI 0.01 to 3.14, low quality evidence). Five participants taking pyridoxal 5 phosphate withdrew from the study because they were not willing to take more medications while none of the participants taking placebo discontinued their medications (n = 65, 2 RCTs, RR 8.72, CI 0.51 to 149.75, low quality evidence).There was no significant difference in the endpoint positive and negative psychiatric symptoms scores, measured using the Positive and Negative symptoms Scale (PANSS) between participants taking pyridoxal 5 phosphate and those taking placebo. For the positive symptoms: (n = 15, 1 RCT, MD -1.50, CI -4.80 to 1.80, low quality evidence). For negative the symptoms: (n = 15, 1 RCT, MD -1.10, CI -5.92 to 3.72, low quality evidence).
AUTHORS' CONCLUSIONS
Pyridoxal 5 phosphate may have some benefits in reducing the severity of tardive dyskinesia symptoms among individuals with schizophrenia. However, the quality of evidence supporting the effectiveness of pyridoxal 5 phosphate in treating tardive dyskinesia is low, based on few studies, short follow-up periods, small sample sizes and inadequate adherence to standardised reporting guidelines for randomised controlled trials among the included studies.
Topics: Adult; Aged; Antipsychotic Agents; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Pyridoxal Phosphate; Randomized Controlled Trials as Topic; Schizophrenia; Vitamin B Complex
PubMed: 25866243
DOI: 10.1002/14651858.CD010501.pub2 -
PloS One 2017Pyridoxal 5'-phosphate (PLP) is an essential cofactor for numerous enzymes involved in a diversity of cellular processes in living organisms. Previous analysis of the...
Pyridoxal 5'-phosphate (PLP) is an essential cofactor for numerous enzymes involved in a diversity of cellular processes in living organisms. Previous analysis of the Actinobacillus pleuropneumoniae S-8 genome sequence revealed the presence of pdxS and pdxT genes, which are implicated in deoxyxylulose 5-phosphate (DXP)-independent pathway of PLP biosynthesis; however, little is known about their roles in A. pleuropneumoniae pathogenicity. Our data demonstrated that A. pleuropneumoniae could synthesize PLP by PdxS and PdxT enzymes. Disruption of the pdxS and pdxT genes rendered the pathogen auxotrophic for PLP, and the defective growth as a result of these mutants was chemically compensated by the addition of PLP, suggesting the importance of PLP production for A. pleuropneumoniae growth and viability. Additionally, the pdxS and pdxT deletion mutants displayed morphological defects as indicated by irregular and aberrant shapes in the absence of PLP. The reduced growth of the pdxS and pdxT deletion mutants under osmotic and oxidative stress conditions suggests that the PLP synthases PdxS/PdxT are associated with the stress tolerance of A. pleuropneumoniae. Furthermore, disruption of the PLP biosynthesis pathway led to reduced colonization and attenuated virulence of A. pleuropneumoniae in the BALB/c mouse model. The data presented in this study reveal the critical role of PLP synthases PdxS/PdxT in viability, stress tolerance, and virulence of A. pleuropneumoniae.
Topics: Actinobacillus pleuropneumoniae; Animals; Female; Gene Knockout Techniques; Hydrogen Peroxide; Ligases; Mice; Mice, Inbred BALB C; Microbial Viability; Mutation; Pyridoxal Phosphate; Sodium Chloride; Stress, Physiological; Virulence
PubMed: 28448619
DOI: 10.1371/journal.pone.0176374 -
Plant Physiology and Biochemistry : PPB Sep 2020Salinity-induced ethylene accumulation caused by high production of 1-aminocyclopropane-1-carboxylic acid (ACC) hinders rice plant growth and development. Nevertheless,...
Salinity-induced ethylene accumulation caused by high production of 1-aminocyclopropane-1-carboxylic acid (ACC) hinders rice plant growth and development. Nevertheless, ACC deaminase may alleviate salt stress and high ethylene production in rice cultivars under salinity stress. Pyridoxal 5'-phosphate (PLP), an ACC deaminase co-factor, could be a useful ACC inhibitor in plants; however, it has not been studied before. In the present study, the effects of PLP on the growth and morphophysiological characteristics of rice cultivars (Jinyuan 85 (JY85) and Nipponbare (NPBA) were investigated under salinity stress (control (CK), low salinity (LS), and high salinity (HS) in hydroponic conditions. The experiment was laid out in a completely randomized design (CRD) under factorial arrangement of treatments. The results showed that, compared with no PLP, exogenous application of PLP significantly inhibited ACC and ethylene production in the roots, leaves and panicles of both cultivars under salinity, and PLP was more effective at improving the physiological characteristics of both cultivars under salinity stress. Further, root morphophysiological traits and pollen viability were triggered in the PLP treatment compared to the no-PLP treatment under various salinity levels. ACC production inhibited by PLP was useful for improving the 1000-grain weight, grain yield per plant, and total plant biomass under the CK, LS and HS treatments in both rice cultivars. These results revealed that PLP, as an ACC deaminase cofactor, is a key tool for mitigating ethylene-induced effects under salinity stress and for enhancing the agronomic and morphophysiological traits of rice under saline conditions.
Topics: Carbon-Carbon Lyases; Ethylenes; Oryza; Pyridoxal Phosphate; Salinity; Salt Stress
PubMed: 32680726
DOI: 10.1016/j.plaphy.2020.05.035 -
Preparative Biochemistry & Biotechnology 2022Pyridoxal 5'-phosphate (PLP) is the coenzyme of more than 140 enzymes and is widely used in various fields. In this study, to enhance the production of PLP in BL21, the...
Pyridoxal 5'-phosphate (PLP) is the coenzyme of more than 140 enzymes and is widely used in various fields. In this study, to enhance the production of PLP in BL21, the recombinant strain BL21/pETDuet-1-pdxj-zwf-dxs was constructed. The concentration of PLP in this strain was 82.69 mg/L, which was increased by 1.38-fold as compared to that in BL21. Glucose, yeast extract, and pH had an obvious impact on the concentration of PLP, and their optimal levels were 34.89 g/L, 31.17 g/L, and 10.07, respectively. The concentration of PLP under the optimal condition reached 2.23 g/L. The time-course analysis showed that the highest concentration of PLP was 2.32 g/L in recombinant strain after the induction for 12 h by 0.1 mM IPTG in a 1 L shake flask, which was increased by 38.76-fold as compared to that in BL21. This study provides a good basis for the efficient production of PLP in BL21.
Topics: Escherichia coli; Escherichia coli Proteins; Ligases; Phosphates; Pyridoxal Phosphate
PubMed: 34431758
DOI: 10.1080/10826068.2021.1966801 -
Journal of the National Cancer Institute Mar 2017Vitamin B6 is involved in many biochemical reactions and might play a role in carcinogenesis. We summarized the evidence linking vitamin B6 to cancer risk. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vitamin B6 is involved in many biochemical reactions and might play a role in carcinogenesis. We summarized the evidence linking vitamin B6 to cancer risk.
METHODS
We conducted a systematic review of both observational and intervention studies investigating the relationship between vitamin B6 intake or blood levels of its bioactive form pyridoxal-5'-phosphate (PLP) and the risk of any type of cancer. Random-effects meta-analysis was used to calculate pooled relative risks (RRs) and their 95% confidence intervals (CIs) across studies for high vs low categories of vitamin intake or PLP levels. We also performed a random-effects dose-response meta-analysis.
RESULTS
We identified 121 observational studies (participants, n = 1 924 506; cases, n = 96 , 436) and nine randomized controlled trials (RCTs; participants, n = 34 911; cases, n = 2539) considering 19 tumor sites. High intake of dietary (food only) vitamin B6 was statistically significantly associated with lower risk of all cancers (relative risk [RR] = 0.78, 95% CI = 0.73 to 0.84) and specific tumors, with special regard to gastrointestinal carcinomas (RR = 0.68, 95% CI = 0.61 to 0.75). An inverse association was also observed between high PLP levels and the risk of all cancers (RR = 0.66, 95% CI = 0.58 to 0.76) and single tumor sites, the most consistent results being those for gastrointestinal tumors (RR = 0.56, 95% CI = 0.48 to 0.65). There was a statistically significant inverse linear relationship between cancer risk and both vitamin B6 dietary intake and PLP levels. When total (food and supplements) intake was considered, the associations were weaker or null. Findings from RCTs did not support a protective effect of vitamin B6 against cancer, although this evidence was graded as low level.
CONCLUSIONS
Epidemiological evidence supports the potential of vitamin B6 as a cancer risk reduction agent and the role of PLP as a cancer screening biomarker, especially for gastrointestinal tumors. However, inconsistent findings from total intake and intervention studies suggest that vitamin B6 might also be an indicator of other dietary protective micronutrients.
Topics: Diet; Dose-Response Relationship, Drug; Humans; Neoplasms; Observational Studies as Topic; Protective Factors; Pyridoxal Phosphate; Randomized Controlled Trials as Topic; Risk Assessment; Vitamin B 6
PubMed: 28376200
DOI: 10.1093/jnci/djw230 -
Proceedings of the National Academy of... Oct 2021The mechanism by which molecular oxygen is activated by the organic cofactor pyridoxal phosphate (PLP) for oxidation reactions remains poorly understood. Recent work has...
The mechanism by which molecular oxygen is activated by the organic cofactor pyridoxal phosphate (PLP) for oxidation reactions remains poorly understood. Recent work has identified arginine oxidases that catalyze desaturation or hydroxylation reactions. Here, we investigate a desaturase from the indolmycin pathway. Our work, combining X-ray crystallographic, biochemical, spectroscopic, and computational studies, supports a shared mechanism with arginine hydroxylases, involving two rounds of single-electron transfer to oxygen and superoxide rebound at the 4' carbon of the PLP cofactor. The precise positioning of a water molecule in the active site is proposed to control the final reaction outcome. This proposed mechanism provides a unified framework to understand how oxygen can be activated by PLP-dependent enzymes for oxidation of arginine and elucidates a shared mechanistic pathway and intertwined evolutionary history for arginine desaturases and hydroxylases.
Topics: Amino Acid Oxidoreductases; Catalytic Domain; Crystallography, X-Ray; Evolution, Chemical; Mixed Function Oxygenases; Protein Conformation; Pyridoxal Phosphate
PubMed: 34580201
DOI: 10.1073/pnas.2012591118 -
Yakugaku Zasshi : Journal of the... 2019Overconsumption of Ginkgo biloba seeds induces food poisoning characterized by tonic-clonic convulsions and vomiting. The primary toxic component, 4'-O-methylpyridoxine... (Review)
Review
Overconsumption of Ginkgo biloba seeds induces food poisoning characterized by tonic-clonic convulsions and vomiting. The primary toxic component, 4'-O-methylpyridoxine (MPN), was purified from the seeds in 1985. This review includes the following aspects of ginkgo seed poisoning: 1) toxicity related to the content of MPN and MPN glucoside in G. biloba seeds; 2) the effect of MPN on vitamin B analogs, including an increase in pyridoxal and pyridoxic acid and decrease in pyridoxal-5'-phosphate plasma concentrations; 3) case reports of ginkgo seed poisoning in Asia, North America, and Europe, and their effective treatment via vitamin B administration. Considering the increase in the use of G. biloba seeds, it is essential to raise global awareness of their potential toxicity.
Topics: Foodborne Diseases; Ginkgo biloba; Humans; Pyridoxal Phosphate; Pyridoxic Acid; Pyridoxine; Vitamin B 6; Vitamin B 6 Deficiency
PubMed: 30606915
DOI: 10.1248/yakushi.18-00136 -
Nature Metabolism Jun 2024Oxygen is critical for all metazoan organisms on the earth and impacts various biological processes in physiological and pathological conditions. While oxygen-sensing...
Oxygen is critical for all metazoan organisms on the earth and impacts various biological processes in physiological and pathological conditions. While oxygen-sensing systems inducing acute hypoxic responses, including the hypoxia-inducible factor pathway, have been identified, those operating in prolonged hypoxia remain to be elucidated. Here we show that pyridoxine 5'-phosphate oxidase (PNPO), which catalyses bioactivation of vitamin B6, serves as an oxygen sensor and regulates lysosomal activity in macrophages. Decreased PNPO activity under prolonged hypoxia reduced an active form of vitamin B6, pyridoxal 5'-phosphate (PLP), and inhibited lysosomal acidification, which in macrophages led to iron dysregulation, TET2 protein loss and delayed resolution of the inflammatory response. Among PLP-dependent metabolism, supersulfide synthesis was suppressed in prolonged hypoxia, resulting in the lysosomal inhibition and consequent proinflammatory phenotypes of macrophages. The PNPO-PLP axis creates a distinct layer of oxygen sensing that gradually shuts down PLP-dependent metabolism in response to prolonged oxygen deprivation.
Topics: Lysosomes; Macrophages; Animals; Mice; Pyridoxal Phosphate; Hypoxia; Cell Hypoxia; Vitamin B 6; Oxygen; Inflammation
PubMed: 38822028
DOI: 10.1038/s42255-024-01053-4 -
Expert Opinion on Drug Metabolism &... Nov 2020Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the western world. Despite extensive investigations into the mechanisms of cell death,... (Review)
Review
INTRODUCTION
Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the western world. Despite extensive investigations into the mechanisms of cell death, only a single antidote, N-acetylcysteine, is in clinical use. However, there have recently been more efforts made to translate mechanistic insight into identification of therapeutic targets and potential new drugs for this indication.
AREAS COVERED
After a short review of the key events in the pathophysiology of APAP-induced liver injury and recovery, the pros and cons of targeting individual steps in the pathophysiology as therapeutic targets are discussed. While the re-purposed drug fomepizole (4-methylpyrazole) and the new entity calmangafodipir are most advanced based on the understanding of their mechanism of action, several herbal medicine extracts and their individual components are also considered.
EXPERT OPINION
Fomepizole (4-methylpyrazole) is safe and has shown efficacy in preclinical models, human hepatocytes and in volunteers against APAP overdose. The safety of calmangafodipir in APAP overdose patients was shown but it lacks solid preclinical efficacy studies. Both drugs require a controlled phase III trial to achieve regulatory approval. All studies of herbal medicine extracts and components suffer from poor experimental design, which questions their clinical utility at this point.
Topics: Acetaminophen; Acetylcysteine; Animals; Antidotes; Chemical and Drug Induced Liver Injury; Drug Overdose; Edetic Acid; Fomepizole; Hepatocytes; Humans; Liver Failure, Acute; Pyridoxal Phosphate
PubMed: 32862728
DOI: 10.1080/17425255.2020.1817896