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At least 739 records · Page 41Linked to original sources
PubMed1995

Ca(2+)- and nitric oxide-dependent stimulation of cyclic GMP synthesis in neuronal cell line induced by P2-purinergic/pyrimidinergic receptor.

The mechanism by which cyclic GMP synthesis is activated through a nucleotide receptor was studied in mouse neuroblastoma x rat glioma hybrid cells [108CC15 (NG 108-15)]. The transient increase in cyclic GMP level induced by ATP reached its maximum at 20 s and lasted for approximately 1 min. The maximal rise in cyclic GMP level achieved was highest for ATP and decreased in the following order: ATP = adenosine 5'(gamma-thio)triphosphate > UTP = 2-methylthio-ATP > ADP much greater than CTP, AMP, alpha,beta-methylene-ATP, 2'- and 3'-O-(4-benzoylbenzoyl)ATP. The EC50 of 1 +/- 0.2 microM for UTP was significantly lower than that for ATP (14 +/- 8 microM) and for all the other nucleotides tested. The rank order of potency is consistent with the pharmacology of a P2u receptor. At submaximal concentrations of the nucleotides ATP and UTP, the rise in cyclic GMP level was inhibited by suramin (IC50 = 40-60 microM) or the pyridoxal phosphate analogue pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (IC50 = 20-30 microM). Pretreatment of cells with the Ca2+ ionophore ionomycin or with 2,5-di(tert-butyl)-1,4-benzohydroquinone, an inhibitor of Ca(2+)-ATPase in the endoplasmic reticulum, a maneuver to deplete internal Ca2+ stores, suppressed the ATP- or UTP-induced stimulation of cyclic GMP synthesis. Similarly, loading of the cells with the Ca2+ chelator 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid inhibited cyclic GMP formation by ATP. Preincubation with forskolin to raise the cyclic AMP level potentiated the ATP-induced rise in cyclic GMP level by 60%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1994

The influence of protein intake on vitamin B-6 metabolism differs in young and elderly humans.

Vitamin B-6 metabolism was studied as a function of dietary protein intake. Subjects were 29 young adults (29 +/- 1 y old) and 26 elderly adults (70 +/- 1 y old) who consumed standardized diets containing 12% (Diet A) and 21% (Diet B) of total energy as protein for 3 wk each, according to a randomized crossover design. Vitamin B-6 intake for young and elderly subjects was 1.52 +/- 0.08 mg/d (21.74 +/- 0.45 micrograms/g protein) and 1.47 +/- 0.05 mg/d (23.81 +/- 0.08 micrograms/g protein), respectively, during consumption of Diet A and 1.79 +/- 0.07 mg/d (14.49 +/- 0.11 micrograms/g protein) and 1.73 +/- 0.05 mg/d (16.24 +/- 0.06 micrograms/g protein) during consumption of Diet B. Plasma pyridoxal phosphate (PLP), pyridoxal and total vitamin B-6 concentrations were significantly lower in the elderly subjects compared with the young adult subjects during both diet periods. In the elderly subjects, PLP was significantly higher during Diet B consumption (Diet A: 27 +/- 3 nmol/L; Diet B: 32 +/- 3 nmol/L), whereas the level of protein intake had no significant effect on plasma PLP in the young adults (Diet A: 47 +/- 6 nmol/L; Diet B: 45 +/- 5 nmol/L). Plasma pyridoxal and plasma total vitamin B-6 concentrations were not influenced by the amount of protein intake in young and elderly subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Serum vitamin B6 in schizophrenic and schizoaffective patients with and without tardive dyskinesia.

There are several reports regarding the efficacy of vitamin B6 in the treatment of tardive dyskinesia (TD). Vitamin B6 plays a key role in the synthesis of several neurotransmitters, including serotonin, dopamine, norepinephrine, and gamma-aminobutyric acid, all of which have been proposed to be involved in the development of TD. The purpose of this study was to examine whether there are special markers to distinguish long-term neuroleptic exposure patients who have TD from those patients who do not develop this side effect. In view of the pivotal role of vitamin B6 in the synthesis of all neurotransmitters believed to take part in the pathogenesis of TD, we decided to examine whether basal levels of vitamin B6 might explain the difference between these two groups. Such a finding could provide a predictive marker for vulnerable patients. The active metabolite of vitamin B6 is pyridoxal phosphate (PP). Pyridoxal phosphate blood levels were measured in 15 schizophrenic and schizoaffective patients with TD and compared with 15 patients without evidence of TD (matched by sex, age, smoking, and diagnosis). We found that, although patients in the TD group were exposed to neuroleptic drugs for significantly longer periods of time, there were no differences in serum PP levels between the groups. The reports of the effectiveness of vitamin B6 supplementation in the treatment of TD could therefore be explained by the assumption that central nervous system or intracellular vitamin B6 levels, which are involved in the pathogenesis of TD, are not the same as vitamin B6 peripheral serum levels. There is need for further studies, which will clarify the relationship between vitamin B6 and TD.

Adult↗
PubMed1995

Effect of pyridoxal 5'-phosphate on human neutrophil aggregation in vitro.

Pyridoxal 5'-phosphate inhibited polymorphonuclear leukocyte aggregation in vitro in a dose-dependent fashion at concentrations ranging from 0.5 to 0.001 mmol/l. At pyridoxal 5'-phosphate concentrations between 0.4 and 0.5 mmol/l mean inhibition of aggregation was about 50%-60%. In this range, and at lower pyridoxal 5'-phosphate concentrations, phorbol myristate acetate-activated polymorphonuclear leukocytes showed a normal increase in volume, whereas swelling was inhibited at higher concentrations of pyridoxal 5'-phosphate. Since pyridoxal 5'-phosphate can be administered as a vitamin to man without any relevant side-effects its role as a physiological anti-aggregant of polymorphonuclear leukocytes warrants further investigation.

Adult↗
PubMed1987

[Interaction of pyridoxal-5-phosphate with human serum albumin and pancreatic ribonuclease].

Pyridoxal-5-phosphate (in a lesser degree, pyridoxal) interacts with both non-protonated and protonated exposed epsilon-amino groups of lysine residues and with alpha-amino groups in human serum albumin and pancreatic ribonuclease A. The reaction of Schiff base formation proceeds within a wide pH range--from 3.0 to 12.0. At a great pyridoxal-5-phosphate excess in ribonuclease A in neutral or slightly acidic aqueous media all the ten epsilon-amino groups of lysine residues and the alpha-amino groups of Lys-1 become modified. The formation of aldimine bonds of pyridoxal-5-phosphate with protonated amino groups in acidic media is determined by ionization of its phenol hydroxyl and phosphate residues. Acetaldehyde, propionic aldehyde and pyridine aldehyde interact only with non-protonated amino groups of the proteins. The equilibrium constants of pyridoxal-5-phosphate and other aldehydes binding to proteins and amino acids were determined. The rate constants of Schiff base formation for pyridoxal-5-phosphates with some amino acids and primary sites of proteins for direct and reverse reactions were calculated.

Alkylation↗
PubMed1975

Biphasic inactivation of procine heart mitochondrial malate dehydrogenase by pyridoxal 5'-phosphate.

Temperature studies have indicated that from 0 to 37 degrees, the time-dependent inactivation of mitochondrial malate dehydrogenase from porcine heart by pyridoxal 5-phosphate (pyridoxal-5-P) is biphasic. The initial phase of the inactivation is reversible but can be made irreversible by reduction with sodium borohydride. The reduced pryidoxal-5-P-enzyme adduct exhibits a new absorbance maximum at 325 nm and a fluorescence emission at 392 nm when excited at 325. The irreversible second phase of the inactivation is accompanied by the appearance of a new 325-nm absorbance maximum, in the absence of reduction, and a fluorescence emission centered about 390 to 400 nm when excited at 325. The evidence presented suggests the formation of a Schiff base between pyridoxal-5-P and a nucleophilic residue, most likely lysine, of malate dehydrogenase during the first phase of inactivation. An X-azolidine-like structure, a further derivative of the Schiff base, possessing spectral properties consistent with the reported data, may be formed during the second phase; this presumably involves a second nucleophilic residue of the enzyme, implicating the action of pyridoxal-5-P as a bifunctional reagent in this instance. The presence of the coenzyme, NADH, protects the enzyme from inactivation, suggesting that pyridoxal-5-P interacts at or near the malate dehydrogenase active center. Simultaneous binding studies using pyridoxal-5-P with known malate dehydrogenase competitive inhibitors AMP, ADP, and nicotinamide indicate that the pyridoxal-5-P modification occurs in the general area of the ADP portion of the coenzyme binging site. Furthermore, the presence of nicotinamide enhances pyridoxal-5-P binding to and inactivation of malate dehydrogenase.

Animals↗
PubMed1995

Essential lysine residue in glutathione reductase: chemical modification by pyridoxal 5'-phosphate.

Yeast glutathione reductase was inactivated by pyridoxal 5'-phosphate. The inhibition was reversed by dilution. The enzyme-pyridoxal 5'-phosphate complex on reduction with sodium borohydride gave a characteristic absorption maximum at 325 nm and fluorescence maximum at 395 nm when exciated at 325 nm. These results were consistent with the reaction of epsilon-amino group of lysine residue of the enzyme with pyridoxal 5'-phosphate. The enzyme was protected against pyridoxal 5'-phosphate inhibition by NADP indicating thereby that the essential lysine residues are present during the NADP binding site.

Adenosine Monophosphate↗
PubMed1997

Biological role of carbamoyl pyridoxal 5'-phosphate.

A new compound, carbamoyl-pyridoxal 5'-phosphate (C-PLP), was synthetized by condensation of pyridoxal 5'-phosphate (PLP) with KCNO. It may be obtained under certain physiological conditions of pH, temperature and concentration of reagents. Formation and degradation of C-PLP are readily reversible chemical reactions, not involving enzymes, at least in rat tissues. However, different considerations suggest that synthesis and breakdown of C-PLP play a biological role in the cell, providing 'protective synthesis' and a 'variable reservoir' of PLP and KCNO, which can be trapped by other proteins, apoenzymes and metabolites, to regulate many cell metabolic functions.

Animals↗
PubMed1981

Anticonvulsant activity of muscimol and gamma-aminobutyric acid against pyridoxal phosphate-induced epileptic seizures.

The intracerebroventricular injection of pyridoxal phosphate (PLP, 0.125-1.25 mumol/rat) causes epileptic seizures (4 min leads to 1 min) that are preventable or reversible by GABA (1 mumol/rat), by muscimol (0.025 mumol/rat), or by diazepam (1.75 mumol/rat). At the peak of PLP-induced convulsions, the activities of GAD and GABA-T in 14 regions of rat brain remained unaltered, whereas the concentrations of PLP remained elevated. The PLP-induced convulsion was blocked by DABA (10 mumol/rat) but was not altered by beta-alanine (50 mumol/rat). The previous in vitro studies have shown that PLP increases the uptake of [3H]GABA into synaptosomes and inhibits the binding of [3H]GABA to synaptic membranes. These data suggest that PLP-induced convulsion is due to reduced availability of GABA to its recognition sites, rather than to alteration in the activity of GABA metabolizing enzymes, or unavailability of PLP as a coenzyme for GAD and GABA-T. Since the duration of PLP-induced epileptic seizures is short and can be prevented by GABA agonists, PLP may be used as a tool to study the nature of GABA-mediated neuroinhibition and the properties of GABA receptor sites.

Animals↗
PubMed1985

Pyridoxal phosphate-induced dissociation of the succinate: ubiquinone reductase.

Treatment of the soluble ubiquinone-deficient succinate: ubiquinone reductase with pyridoxal phosphate results in the inhibition of the carboxin-sensitive ubiquinone-reductase activity of the enzyme. The inactivation is prevented by the soluble homolog of ubiquinone (Q2) but is insensitive to the dicarboxylates interacting with the substrate binding site of succinate dehydrogenase. The reactivity of the pyridoxal phosphate-inhibited enzyme with different electron acceptors suggests that the observed inhibition is due to the dissociation of succinate dehydrogenase from the enzyme complex. The soluble succinate dehydrogenase was recovered in the supernatant after treatment of the insoluble succinate: ubiquinone reductase with pyridoxal phosphate. The data obtained strongly suggest the participation of amino groups in the interaction between succinate dehydrogenase and the ubiquinone reactivity conferring peptide within the complex.

Animals↗
PubMedDate not supplied

The status of vitamin B6 metabolism in brains of genetically epilepsy-prone rats.

The status of vitamin B6 in brains of genetically epilepsy-prone and epilepsy-resistant rats was ascertained by measuring the concentrations of pyridoxal phosphate and the activities of pyridoxal kinase in the hippocampus, basal ganglia, cerebellum, and cerebral cortex, as well as in the entire brain. The concentrations of pyridoxal phosphate in whole brain of control rats and seizure-prone rats did not vary significantly from each other and were 1.2 +/- 0.02 and 1.2 +/- 0.03 microgram/g, respectively. Similarly, the activities of pyridoxal kinase in brains of the two groups were uniform and had values of 3.6 +/- 0.1 and 3.5 +/- 0.06 microgram pyridoxal phosphate formed/mg protein/15 min, respectively. Unlike in the whole brain, the concentration of pyridoxal phosphate in the cerebral cortex of seizure-prone rats was lower (1.24 +/- 0.026 microgram/g) than that of seizure-resistant rats (1.47 +/- 0.23 microgram/g). The opposite was noted in the cerebellum. The concentrations of pyridoxal phosphate in the hippocampus and in the basal ganglion of seizure-prone and seizure-resistant rats were identical. The activities of pyridoxal kinase in the basal ganglion (3.84 +/- 0.23 vs. 4.99 +/- 0.11 microgram pyridoxal phosphate/mg protein/15 min) and in the cerebral cortex (3.40 +/- 0.06 vs. 3.70 +/- 0.04 microgram pyridoxal phosphate/mg protein/15 min) were lower in seizure-prone rats than in seizure-resistant rats. The reverse took place in the hippocampus and in the cerebellum. No uniform associations among the concentration of pyridoxal phosphate, the activity of pyridoxal kinase, and the susceptibility or lack of susceptibility to seizure could be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Physical and enzymological interaction of Bacillus subtilis proteins required for de novo pyridoxal 5'-phosphate biosynthesis.

Bacillus subtilis synthesizes pyridoxal 5'-phosphate, the active form of vitamin B(6), by a poorly characterized pathway involving the yaaD and yaaE genes. The pdxS (yaaD) mutant was confirmed to be a strict B(6) auxotroph, but the pdxT (yaaE) mutant turned out to be a conditional auxotroph depending on the availability of ammonium in the growth medium. The PdxS and PdxT proteins copurified during affinity chromatography and apparently form a complex that has glutaminase activity. PdxS and PdxT appear to encode the synthase and glutaminase subunits, respectively, of a glutamine amidotransferase of as-yet-unknown specificity essential for B(6) biosynthesis.

Anthranilate Synthase↗
PubMed1995

Trypanosoma brucei brucei: uptake and metabolism of pyridoxine and pyridoxal.

The uptake and metabolism of the B6 vitamers pyridoxine and pyridoxal by T. brucei (TREU 55) was investigated. The results show that these vitamers are taken up by simple diffusion followed by metabolic trapping. Both pyridoxine and pyridoxal were found to be metabolised to pyridoxal phosphate in whole cells. The majority of pyridoxal taken up appears to remain as pyridoxal (perhaps protein bound) the remainder being slowly phosphorylated to pyridoxal phosphate by pyridoxal kinase. The majority of pyridoxine taken up was found to be rapidly metabolised to pyridoxal. Evidence was also found supporting the hypothesis that pyridoxine may be phosphorylated to pyridoxal phosphate and then rapidly converted to pyridoxal phosphate.

Alkaline Phosphatase↗
PubMed1978

Interaction of pyridoxal 5-phosphate with apo-serine hydroxymethyltransferase.

The interaction of pyridoxal 5-phosphate with beef liver serine hydroxymethyltransferase (5,10-methylenetetrahydrofolate:glycine hydroxymethyltransferase, EC 2.1.2.1) has been investigated using sedimentation velocity, kinetic and equilibrium techniques. No evidence for an aggregating system could be found in sedimentation velocity experiments in the presence or absence of pyridoxal 5-phosphate. Reassociation of pyridoxal 5-phosphate with apoenzyme and reacquisition of enzymic activity follow identical kinetics. An initial fast step is followed by a second order process with a rate constant of 66 M-1. s-1. A dissociation constant of 27.5 micrometer was obtained from equilibrium studies. No interaction of binding sites was exposed by altering pH or in the presence of glycine or folate. Maxima observed in pH profiles with both binding and reactivation are interpreted as the composite fo two overlapping processes, one of which is ionization of the pyridinium nitrogen of pyridoxal 5-phosphate and the other a functional group on the apoenzyme. Evidence is presented to indicate the necessity for the formation of an enzyme . pyridoxal 5-phosphate Schiff's base complex during catalytic turnover.

Apoenzymes↗
PubMed1985

Effect of modification of lysine residues of fructose-6-phosphate 2-kinase:fructose-2,6-bisphosphatase with pyridoxal 5'-phosphate.

Inactivation of a bifunctional enzyme, fructose-6-P,2-kinase:fructose-2,6-bisphosphatase by pyridoxal 5'-P followed by reduction with NaBH4 was studied. Fructose-6-P,2-kinase is over 80% inactivated by 2 mM pyridoxal 5'-P. The stoichiometry of the pyridoxyl-P incorporation and the inactivation of the kinase follows a biphasic curve. The first P-pyridoxyl residue incorporated per protomer does not affect fructose-6-P,2-kinase, but the next two P-pyridoxyl incorporation/protomer results in 80% inactivation. The Km values for ATP and fructose-6-P of the enzymes containing varying amounts of P-pyridoxyl groups at intermediate levels of inactivation are not altered, but Vmax is decreased. Among the metabolites tested, only fructose-2,6-P2 and Mg-ATP are competitive with pyridoxal-P and protect the enzyme against the inactivation. Neither the activity nor the fructose-6-P inhibition of fructose-2,6-bisphosphatase is affected by the modification. The acid hydrolysate of the inactive P-[3H]pyridoxyl enzyme contained only [3H]pyridoxyl lysine. High performance liquid chromatography of tryptic peptides of phospho[3H]pyridoxyl enzymes reveals two peptides which were missing in the enzyme protected by fructose-2,6-P2 or ATP during the modification reaction. These peptides have been isolated, and their amino acid sequences have been determined as Asp-Gln-Asp-Lys-Tyr-Arg and Asp-Val-His-Lys-Tyr. Pyridoxal-P reacts specifically with two lysine residues at the fructose-2,6-P2-binding site of fructose-6-P,2-kinase but not that of fructose-2,6-bisphosphatase. The site may also overlap with the ATP-binding site.

Adenosine Triphosphate↗
PubMed1982

Dual effects f pyridoxal 5'-phosphate on glucocorticoid-receptor complexes.

The ability of pyridoxal 5'-phosphate to inhibit DNA-cellulose binding of activated glucocorticoid-receptor complexes is pH and protein concentration dependent. At the tested pHs, all of the inhibitory activity of pyridoxal 5'- phosphate appears to be due to its ability to form a Schiff base. 2-Amino-2-(hydroxymethyl)-1,3-propanediol (100 mM) is unable to prevent or reverse the pyridoxal 5'-phosphate mediated inhibition of DNA-cellulose binding, while the same concentration of lysine is partially effective. Pyridoxal 5'-phosphate does not alter the elution profile of glucocorticoid-receptor complexes as ascertained by diethylaminoethyl (DEAE)-cellulose of DEAE-Sephadex chromatography. This observation permitted the use of these resins in detecting the previously unreported stimulation of glucocorticoid-receptor complex activation by pyridoxal 5'-phosphate. This stimulation is specific for pyridoxal 5'-phosphate and appears to be mediated via a Schiff base formation. Additionally, glucocorticoid-receptor complexes activated by pyridoxal 5'-phosphate treatment at low temperatures do not differ in size from thermally activated complexes. Thus, in vitro, pyridoxal 5'-phosphate can exert both a stimulatory effect on activation as well as an inhibitory effect on the binding of activated complexes to DNA-cellulose.

Animals↗
PubMed1980

Activation and protection from 5-fluorodeoxyuridylate inactivation of mammalian thymidylate synthetase by pyridoxal 5'-phosphate.

Rat liver thymidylate synthetase was partially purified by a combination of (NH4)2SO4 precipitation and Sephadex chromatography. Incubation of these partially purified enzyme preparations with pyridoxal phosphate resulted in as much as a 12-fold increase in enzyme activity. In addition, incubation of partially purified thymidylate synthetase preparations with 5.0 X 10(-5) M pyridoxal phosphate protected the enzyme from 5-fluorodeoxyuridylate inhibition to the extent that 78% of the control activity was retained at 5-fluorodeoxyuridylate concentrations as high as 5.0 X 10(-5) M. These findings are discussed in terms of the reported inhibition of tumour growth in the absence of dietary vitamin B6.

Animals↗