A plausible prebiotic synthesis of pyridoxal phosphate: Vitamin B6 – A computational study

2006 ◽  
Vol 123 (2-3) ◽  
pp. 113-121 ◽  
Author(s):  
Nigel Aylward ◽  
Neville Bofinger
Keyword(s):  
Vitamin B6 ◽  
Pyridoxal Phosphate ◽  
Computational Study ◽  
Prebiotic Synthesis

scholarly journals The Affinity of Carboplatin to B-Vitamins and Nucleobases

2021 ◽  
Vol 22 (7) ◽  
pp. 3634
Author(s):  
Beata Szefler ◽  
Przemysław Czeleń ◽  
Przemysław Krawczyk
Keyword(s):  
Vitamin B6 ◽  
Pyridoxal Phosphate ◽  
Antitumor Agents ◽  
Lone Pair ◽  
Chemical Compounds ◽  
Free Energies ◽  
Aromatic Rings ◽  
Anti Cancer ◽  
Potential Impact ◽  
Reactive Molecule

Platinum compounds have found wide application in the treatment of various types of cancer and carboplatin is one of the main platinum-based drugs used as antitumor agents. The anticancer activity of carboplatin arises from interacting with DNA and inducing programmed cell death. However, such interactions may occur with other chemical compounds, such as vitamins containing aromatic rings with lone-pair orbitals, which reduces the anti-cancer effect of carboplatin. The most important aspect of the conducted research was related to the evaluation of carboplatin affinity to vitamins from the B group and the potential impact of such interactions on the reduction of therapeutic capabilities of carboplatin in anticancer therapy. Realized computations, including estimation of Gibbs Free Energies, allowed for the identification of the most reactive molecule, namely vitamin B6 (pyridoxal phosphate). In this case, the computational estimations indicating carboplatin reactivity were confirmed by spectrophotometric measurements.

COMMITTEE ON NUTRITION

PEDIATRICS ◽  
1966 ◽  
Vol 38 (6) ◽  
pp. 1068-1076
Author(s):  
Keyword(s):  
Vitamin B6 ◽  
Pyridoxal Phosphate ◽  
Normal Population ◽  
Clinical Signs ◽  
Normal Activity ◽  
Limited Information ◽  
Adequate Intake ◽  
Time Data ◽  
Binding Properties ◽  
Adequate Diet

Because of the limited information available it is not possible to derive precise figures for daily requirements of vitamin B6 in infants and children at this time. Data currently available suggest that the daily need in childhood is 0.5 to 1.5 mg and in adolescence is 1.5 to 2 mg. The requirement in infancy is clearly related to protein intake and is 20µg/gm of dietary protein. Requirements of a few individuals will undoubtedly be higher than the estimates for the normal population. Some of these patients will manifest frank biochemical and clinical signs of deficiency which will usually be promptly reversed by administration of small additional amounts of pyridoxine. Another group of patients will require large amounts of the vitamin to balance the heritable alteration in binding properties of a specific apoenzyme requiring pyridoxal phosphate for normal activity. It would appear that most infants, children and adults will have little difficulty in achieving an adequate intake of vitamin B6 if they receive what is considered to be in other respects an adequate diet.

scholarly journals The Alkaline Phosphatase (ALPL) Locus Is Associated with B6 Vitamer Levels in CSF and Plasma

Genes ◽  
2018 ◽  
Vol 10 (1) ◽  
pp. 8 ◽  
Author(s):  
Loes Loohuis ◽  
Monique Albersen ◽  
Simone de Jong ◽  
Timothy Wu ◽  
Jurjen Luykx ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Vitamin B6 ◽  
Pyridoxal Phosphate ◽  
Genome Wide Association Study ◽  
Active Form ◽  
Minor Allele ◽  
Chromosome 1 ◽  
Joint Analysis ◽  
Genome Wide ◽  
A Genome

The active form of vitamin B6, pyridoxal phosphate (PLP), is essential for human metabolism. The brain is dependent on vitamin B6 for its neurotransmitter balance. To obtain insight into the genetic determinants of vitamin B6 homeostasis, we conducted a genome-wide association study (GWAS) of the B6 vitamers pyridoxal (PL), PLP and the degradation product of vitamin B6, pyridoxic acid (PA). We collected a unique sample set of cerebrospinal fluid (CSF) and plasma from the same healthy human subjects of Dutch ancestry (n = 493) and included concentrations and ratios in and between these body fluids in our analysis. Based on a multivariate joint analysis of all B6 vitamers and their ratios, we identified a genome-wide significant association at a locus on chromosome 1 containing the ALPL (alkaline phosphatase) gene (minimal p = 7.89 × 10−10, rs1106357, minor allele frequency (MAF) = 0.46), previously associated with vitamin B6 levels in blood. Subjects homozygous for the minor allele showed a 1.4-times-higher ratio between PLP and PL in plasma, and even a 1.6-times-higher ratio between PLP and PL in CSF than subjects homozygous for the major allele. In addition, we observed a suggestive association with the CSF:plasma ratio of PLP on chromosome 15 (minimal p = 7.93 × 10−7, and MAF = 0.06 for rs28789220). Even though this finding is not reaching genome-wide significance, it highlights the potential of our experimental setup for studying transport and metabolism across the blood–CSF barrier. This GWAS of B6 vitamers identifies alkaline phosphatase as a key regulator in human vitamin B6 metabolism in CSF as well as plasma. Furthermore, our results demonstrate the potential of genetic studies of metabolites in plasma and CSF to elucidate biological aspects underlying metabolite generation, transport and degradation.

The relationship between plasma albumin, alkaline phosphatase and pyridoxal phosphate concentrations in plasma and red cells: Implications for assessing vitamin B6 status

2020 ◽  
Vol 39 (9) ◽  
pp. 2824-2831 ◽  
Author(s):  
Dinesh Talwar ◽  
Anthony Catchpole ◽  
John M. Wadsworth ◽  
Barry J. Toole ◽  
Donald C. McMillan
Keyword(s):  
Alkaline Phosphatase ◽  
Vitamin B6 ◽  
Pyridoxal Phosphate ◽  
Red Cells ◽  
Plasma Albumin ◽  
The Relationship

Pyridoxal phosphate ? The coenzyme form of vitamin B6

1979 ◽  
Vol 13 (10) ◽  
pp. 1097-1100
Author(s):  
M. A. Kovler ◽  
Zh. P. Alekseeva ◽  
T. N. Smirnova ◽  
M. L. Lobanova ◽  
L. A. Shevnyuk ◽  
...  
Keyword(s):  
Vitamin B6 ◽  
Pyridoxal Phosphate ◽  
Coenzyme Form

scholarly journals A Computational Study of a Prebiotic Synthesis of the Steroid Progesterone (A and B Rings)

2020 ◽  
Vol 17 ◽  
Keyword(s):  
Double Bond ◽  
Hydroxyl Radicals ◽  
Computational Study ◽  
Prebiotic Synthesis ◽  
Magnesium Ion ◽  
Methyl Substituent ◽  
Trans Conformation ◽  
Trans Orientation ◽  
Metal Site ◽  
Enthalpy Changes

The magnesium ion metalloporphyrin complex is shown to bind the ligands propyne (p) and ethyne (e) on the metal or nitrogen pyrrole sites as a two site catalyst in their copolymerization. The order of addition of the monomers is (pepeeepee). The steroid ring D (pep) is formed first from the propyne adduct bound to the metal site and the but-diene adduct bound to the N-site. The optimal orientation of these adducts determines the β-orientation of the 17-substituent. Further reaction with hydroxyl radicals allows this to be a 17 β- acetyl substituent. Further addition of three ethyne monomers forms a N-tri-ene cyclopentene derivative able to cyclise to form the steroid ring C (pee) with a trans conformation and a 13-β methyl substituent.. Further binding of propyne on the metal site together with the N-indenyl bound adduct enables the B-ring (eep) to form with a trans orientation and a 10-β-methyl substituent. Further addition of two ethyne monomers to the Mg.porphin.N-phenanthrenyl bound adduct allows cyclisation to form the A-ring (pee). The polymerization is curtailed by reaction with hydroxyl radical to form the 3-keto substituent. The cleavage of the Mg.porphin catalyst produces the double bond of pregnane-4,5-diene-3,20-dione. The reactions have been shown to be feasible from the overall enthalpy changes in the ZKE approximation at the HF and MP2 /6-31G* level, and with acceptable activation energies.

scholarly journals Vitamin B6 Acquisition and Metabolism in Schistosoma mansoni

2021 ◽  
Vol 11 ◽  
Author(s):  
Akram A. Da’dara ◽  
Manal Elzoheiry ◽  
Samar N. El-Beshbishi ◽  
Patrick J. Skelly
Keyword(s):  
Schistosoma Mansoni ◽  
Vitamin B6 ◽  
Pyridoxal Phosphate ◽  
Active Form ◽  
Adult Males ◽  
Pyridoxal Kinase ◽  
Genes Encoding ◽  
Inflammatory Processes ◽  
Survival And Growth ◽  
Males And Females

Schistosomes are parasitic platyhelminths that currently infect >200 million people globally. The adult worms can live within the vasculature of their hosts for many years where they acquire all nutrients necessary for their survival and growth. In this work we focus on how Schistosoma mansoni parasites acquire and metabolize vitamin B6, whose active form is pyridoxal phosphate (PLP). We show here that live intravascular stage parasites (schistosomula and adult males and females) can cleave exogenous PLP to liberate pyridoxal. Of the three characterized nucleotide-metabolizing ectoenzymes expressed at the schistosome surface (SmAP, SmNPP5, and SmATPDase1), only SmAP hydrolyzes PLP. Heat-inactivated recombinant SmAP can no longer cleave PLP. Further, parasites whose SmAP gene has been suppressed by RNAi are significantly impaired in their ability to cleave PLP compared to controls. When schistosomes are incubated in murine plasma, they alter its metabolomic profile—the levels of both pyridoxal and phosphate increase over time, a finding consistent with the action of host-exposed SmAP acting on PLP. We hypothesize that SmAP-mediated dephosphorylation of PLP generates a pool of pyridoxal around the worms that can be conveniently taken in by the parasites to participate in essential, vitamin B6-driven metabolism. In addition, since host PLP‐dependent enzymes play active roles in inflammatory processes, parasite-mediated cleavage of this metabolite may serve to limit parasite-damaging inflammation. In this work we also identified schistosome homologs of enzymes that are involved in intracellular vitamin B6 metabolism. These are pyridoxal kinase (SmPK) as well as pyridoxal phosphate phosphatase (SmPLP-Ph) and pyridox(am)ine 5’-phosphate oxidase (SmPNPO) and cDNAs encoding these three enzymes were cloned and sequenced. The three genes encoding these enzymes all display high relative expression in schistosomula and adult worms suggestive of robust vitamin B6 metabolism in the intravascular life stages.

B-group vitamin supplementation mitigates oxidative damage after acute ischaemic stroke

2004 ◽  
Vol 107 (5) ◽  
pp. 477-484 ◽  
Author(s):  
Rajesh ULLEGADDI ◽  
Hilary J. POWERS ◽  
Salah E. GARIBALLA
Keyword(s):  
Treatment Group ◽  
Oxidative Damage ◽  
Ischaemic Stroke ◽  
Acute Ischaemic Stroke ◽  
Vitamin B6 ◽  
Pyridoxal Phosphate ◽  
Vitamin Supplementation ◽  
Control Group ◽  
Vitamin B2 ◽  
Plasma Thcy

Evidence shows that there is a rapid increase in the production of markers of oxidative damage immediately following acute stroke and that endogenous antioxidant defences are rapidly depleted, thus permitting further tissue damage. Several studies point to an antioxidant effect of B-group vitamins and a pro-oxidant effect of elevated plasma tHcy (total homocysteine). In the present study, we assessed whether supplementary B-group vitamins during this critical period will enhance antioxidant capacity and mitigate oxidative damage. Forty-eight patients with acute ischaemic stroke within 12 h of symptom onset were assigned to receive daily oral supplements of B-group vitamins comprising 5 mg of folate, 5 mg of vitamin B2, 50 mg of vitamin B6 and 0.4 mg of vitamin B12 (n=24) or no supplements (n=24) for 14 days. The treatment group and controls were matched for stroke subtype and age. Blood samples were obtained before intervention and also at 7 and 14 days post-recruitment for measurement of the following biomarkers: red cell folate (whole blood folate corrected with haematocrit), erythrocyte glutathione reductase activity coefficient (EGRAC; measure of vitamin B2 status), plasma pyridoxal phosphate (vitamin B6 status), plasma vitamin B12, plasma α-tocopherol, plasma ascorbic acid, plasma TAOC (total antioxidant capacity), plasma MDA (malondialdehyde), plasma tHcy and CRP (C-reactive protein). Supplementation for 14 days with B-group vitamins significantly increased the plasma concentrations of pyridoxal phosphate and red blood cell folate and improved a measure of B2 status compared with the control group (P<0.05). Plasma tHcy decreased in both groups albeit less in the control group, but differences in cumulative changes were not significant. There was, however, a decrease in plasma MDA concentration in the treatment group, in contrast with the increase seen in the control group and these differences were significant (P=0.05). CRP concentration, a marker of tissue inflammation, was significantly lower in the treatment group compared with controls (P<0.05). In conclusion, B-group vitamin supplementation immediately post-infarct may have antioxidant and anti-inflammatory effects in stroke disease independent of a homocysteine-lowering effect.

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