Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT02288 (NADH)
 21,914 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of the membrane-bound ascorbate-TMPD oxidase in Pseudomonas putida varies with growth conditions and age of the culture. A comparison of the effects of cyanide and azide on the oxidation of various substrates suggests that ascorbate-TMPD oxidase is not the terminal oxidase for NADH or succinate oxidation. However, it does have a role in the oxidation of nicotinate, and may act as an additional terminal oxidase under certain other growth conditions.
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PMID:Physiological role for the membrane bound ascorbate-TMPD oxidase in pseudomonas putida. 16 28

The rates of appearance of FFA (RaFFA) and that of glycerol (RaGLY) were measured simultaneously with [1-14 C]palmitate and [2-3H]-glycerol, in dogs with indwelling arterial and venous catheters. Lipolysis was stimulated by exercise (treadmill run on 10% slope) or by the infusion of norepinephrine (0.5 mug/kg-min). Na-L(+)-lactate (L), Na-pyruvate (Py), or Na-nicotinate (N) were infused. All three components decreased RaFFA. RaGLY was increased by L, unaltered by Py, and decreased by N. There was an inverse correlation (P less than 0.001) between the logarithms of RaFFA and plasma lactate. A linear correlation was obtained between RaGLY and plasma lactate when this latter was increased by the infusion of L. It is suggested that a) lactate in physiological concentrations inhibits the release of FFA stimulated by exercise and b) the increase of the NADH/NAD ratio leads to the formation of alpha-glycerophosphate which in turn yields glycerol. Therefore changes in plasma glycerol do not reflect lipolysis when blood lactate increases. c) The effect of lactate on RaFFA can be explained by an enhanced reesterification, although a direct inhibition on lipase could not be excluded.
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PMID:Effect of lactate on FFA and glycerol turnover in resting and exercising dogs. 117 1

The toxicity of CB 1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide] towards human cells was greatly enhanced by NADH (when foetal calf serum was present in the culture medium) and by nicotinamide riboside (reduced) (NRH), but not by nicotinate riboside (reduced). Co-treatment of human cells with CB 1954 and NADH resulted in the formation of crosslinks in their DNA. The toxicity produced by other DNA crosslinking agents was unaffected by reduced nicotinamide compounds. When caffeine was included in the medium, a reduction in the cytotoxicity of CB 1954 occurred. The toxicity experienced by human cell lines after exposure to CB 1954 and NADH was proportional to their levels of the enzyme DT diaphorase NAD(P)H dehydrogenase (quinone), EC 1.6.99.2. It is concluded that NRH, which we have shown to be a co-factor for rat DT diaphorase (Friedlos et al., Biochem Pharmacol 44: 25-31, 1992), is generated from NADH by enzymes in foetal calf serum, and stimulates the activity of human DT diaphorase towards CB 1954.
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PMID:Potentiation of CB 1954 cytotoxicity by reduced pyridine nucleotides in human tumour cells by stimulation of DT diaphorase activity. 144 31

The effects of large amounts of tryptophan, pyrazinamide, or nicotinic acid in diets on the contents of total NAD (NAD + NADH) and NADP (NADP + NADPH) of various organs were investigated in mice with or without gamma-irradiation. Female C3H/HeN mice were fed one of the following 4 kinds of experimental diets for one week: 1) control diet (20% casein diet containing 3 mg niacin per 100g diet); 2) diet supplemented by 0.5% L-tryptophan (T-diet); 3) diet supplemented by 0.5% L-tryptophan (T-diet); 4) diet supplemented by 0.1% nicotinic acid (NA-diet). Half of the mice in each group were subsequently irradiated with 8 Gy of gamma-ray (60 Co) after 4 h of fasting. Then, the contents of total NAD and NADP in thymus, spleen, kidney, liver, and blood were determined in all animals. The results indicated that NAD content of spleen was higher in PT-group (21.5%) and NA-group (23.2%) than in that of control group. In thymus, however, NAD content of only the PT-group was significantly greater (13.1%) than control. NAD level of kidney was also significantly higher (32.6%) in PT-group. By gamma-irradiation, NAD contents of thymus and spleen of all groups tended to be decreased, but those of kidney and liver were not always reduced. In the latter two organs, significant NAD reduction was shown only in kidney of PT-group and in liver of PT- and NA-groups. Even after irradiation, NAD levels of spleen and thymus in PT- and NA-groups tended to be kept higher than those in irradiated control group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of dietary pyrazinamide, tryptophan, or nicotinic acid and gamma-ray irradiation on levels of NAD and NADP in various organs of mice. 263 75

In cell-free extracts of Pseudomonas ovalis nicotinic acid oxidase is confined to the wallmembrane fraction. It is associated with an electron-transport chain comprising b- and c-type cytochromes only, differing proportions of which are reduced by nicotinate and NADH. CO difference-spectra show two CO-binding pigments, cytochrome o (absorption maximum at 417nm) and another component absorbing maximally at 425nm. Cytochrome o is not reduced by NADH or by succinate but is by nicotinate, which can also reduce the ;425' CO-binding pigment. The effects of inhibitors of terminal oxidation support the idea of two terminal oxidases and a scheme involving the ;425' CO-binding pigment and the other components of the electron-transport chain is proposed.
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PMID:The oxidation of nicotinic acid by Pseudomonas ovalis Chester. The terminal oxidase. 434 18

As a model system for investigating the mechanism of the hepatic NAD-lowering effect of leucine in rats, aerobically grown Saccharomyces carlsbergensis was used in this paper. Tryptophan supplementation of the medium doubled total niacin production by S. carlsbergensis. This elevation in total niacin was mainly due to increases in niacin (14 times) and niacinamide nucleotides (2 times). Among nucleotides, the NAD level doubled whereas NADH, NADP and NADPH levels dropped significantly. Simultaneous supplementation of the medium with leucine suppressed the elevation in total and free niacin levels. In the presence of tryptophan, approximately 50% of the total niacin was secreted in the medium in the form of free niacin, while in the presence of both tryptophan and leucine most of the total niacin remained in the cell. The specific activity of quinolinate phosphoribosyltransferase [EC 2.4.2.19] was not affected by supplementation of the medium with tryptophan and/or leucine. In contrast, the specific activity of nicotinamide deamidase [EC 3.5.1.19] increased fivefold in the presence of tryptophan. Simultaneous supplementation of the medium with leucine tryptophan. Simultaneous supplementation of the medium with leucine suppressed the increase in nicotinamide deamidase. Cellular incorporation of tryptophan was not affected by leucine simultaneously added as a supplement to the medium. Leucine did not have any inhibitory effect on total niacin synthesis from 3-hydroxyanthranilate. From the results, a possible mechanism for the inhibitory effect of leucine on the tryptophan-NAD pathway was discussed.
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PMID:Effect of L-tryptophan and L-leucine on biosynthesis of niacin-related compounds in Saccharomyces carlsbergensis. 621 72

Pyridine nucleotide metabolism has been studied in vivo in a prokaryotic (Escherichia coli) and a eukaryotic (Saccharomyces cerevisiae) system cultured in a medium containing carbon-13-labeled nicotinic acid, followed by NMR detection of the labeled organisms. Chemical exchange between oxidized and reduced nucleotides is found to be sufficiently slow on the NMR time scale to permit the observation of separate resonances corresponding to each redox state. The possibility of significant exchange broadening of reduced pyridine nucleotide resonances under some conditions was further evaluated based on comparative NMR studies utilizing organisms cultured in the presence of either [2-13C]nicotinate or [5-13C]nicotinate. Based on these experiments, it was concluded that broadening as a consequence of intermediate exchange is not significant. Although it was initially anticipated that the carbon-13 resonances arising from the di- and triphosphopyridine nucleotide pools could not be distinguished, the absence of observable resonances corresponding to reduced nucleotides in oxygenated yeast and E. coli cells suggests that the NMR method is fairly specific for determining the redox status of the diphosphopyridine nucleotide pool. Studies of the effects of a variety of perturbations including variation of the oxygen supply, addition of ethanol, and addition of the oxidative phosphorylation uncoupler dinitrophenol have been carried out. Dramatic differences in the response of the catabolic reduction charge, CRC = [NADH]/[NADH] + [NAD+], between the yeast and E. coli cells are observed. The CRC values for the yeast undergo large changes in response to these perturbations which are not observed for the bacterial cells.
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PMID:In vivo studies of pyridine nucleotide metabolism in Escherichia coli and Saccharomyces cerevisiae by carbon-13 NMR spectroscopy. 636 9

An NADH: (acceptor) oxidoreductase from the cytosol of soybean root nodules was purified by ammonium sulfate fractionation, hydroxylapatite adsorption, and Sephacryl S-200 Superfine chromatography. The native molecular weight of the reductase was found to be 100,000 by analytical gel filtration and 83,000 by equilibrium ultracentrifugation. The subunit molecular weight was 54,000 as determined by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis. The pI of the enzyme was 5.5. With ferric leghemoglobin (Lb) as the substrate, nearly identical initial velocities were obtained using either CO or O2 to ligate the enzymatically produced ferrous leghemoglobin. With CO as the ligand in the reaction, the product of the enzyme-catalyzed, NADH-dependent reduction of ferric Lb was spectrally identified as LbCO. Initial velocity was a linear function of increasing enzyme concentration. NADPH was only 31% as effective an electron donor as NADH as determined by initial velocity. The Michaelis constants (Km) for ferric Lba and NADH were 9.5 and 18.8 microM, respectively. Myoglobin, Lba, Lbc1, Lbc2, Lbc3, and Lbd were reduced at similar rates by the reductase. At pH 5.2, acetate-bound ferric Lb and nicotinate-bound ferric Lb were reduced by the enzyme at 83 and 5%, respectively, of rates observed in the absence of these ligands. The rate of enzymatic reduction of ferric Lb was constant between pH 6.5 and 7.6 but increased approximately threefold at pH 5.2. The results indicate that the NADH: (acceptor) oxidoreductase could be identified as a ferric Lb reductase.
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PMID:Ferric leghemoglobin reductase from soybean root nodules. 653 95

In the usual reaction catalyzed by D-amino acid transaminase, cleavage of the alpha-H bond is followed by the reversible transfer of the alpha-NH2 to a keto acid cosubstrate in a two-step reaction mediated by the two vitamin B6 forms pyridoxal 5'-phosphate (PLP) and pyridoxamine 5'-phosphate (PMP). We report here a reaction not on the main pathway, i.e., beta-decarboxylation of D-aspartate to D-alanine, which occurs at 0.01% the rate of the major transaminase reaction. In this reaction, beta-C-C bond cleavage of the single substrate D-aspartate occurs rather than the usual alpha-bond cleavage in the transaminase reaction. The D-alanine produced from D-aspartate slowly inhibits both transaminase and decarboxylase activities, but NADH or NADPH instantaneously prevent D-aspartate turnover and D-alanine formation, thereby protecting the enzyme against inhibition. NADH has no effect on the enzyme spectrum itself in the absence of substrates, but it acts on the enzyme.D-aspartate complex with an apparent dissociation constant of 16 microM. Equivalent concentrations of NAD or thiols have no such effect. The suppression of beta-decarboxylase activity by NADH occurs concomitant with a reduction in the 415-nm absorbance due to the PLP form of the enzyme and an increase at 330 nm due to the PMP form of the enzyme. alpha-Ketoglutarate reverses the spectral changes caused by NADH and regenerates the active PLP form of the enzyme from the PMP form with an equilibrium constant of 10 microM. In addition to its known role in shuttling electrons in oxidation-reduction reactions, the niacin derivative NADH may also function by preventing aberrant damaging reactions for some enzyme-substrate intermediates. The D-aspartate-induced effect of NADH may indicate a slow transition between protein conformational studies if the reaction catalyzed is also slow.
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PMID:The ubiquitous cofactor NADH protects against substrate-induced inhibition of a pyridoxal enzyme. 897 63

Beyond its role as an essential coenzyme in numerous oxidoreductase reactions as well as respiration, there is growing recognition that NAD+ fulfills many other vital regulatory functions both as a substrate and as an allosteric effector. This review describes the enzymes involved in pyridine nucleotide metabolism, starting with a detailed consideration of the anaerobic and aerobic pathways leading to quinolinate, a key precursor of NAD+. Conversion of quinolinate and 5'-phosphoribosyl-1'-pyrophosphate to NAD+ and diphosphate by phosphoribosyltransferase is then explored before proceeding to a discussion the molecular and kinetic properties of NMN adenylytransferase. The salient features of NAD+ synthetase as well as NAD+ kinase are likewise presented. The remainder of the review encompasses the metabolic steps devoted to (a) the salvaging of various niacin derivatives, including the roles played by NAD+ and NADH pyrophosphatases, nicotinamide deamidase, and NMN deamidase, and (b) utilization of niacins by nicotinate phosphoribosyltransferase and nicotinamide phosphoribosyltransferase.
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PMID:Enzymology of NAD+ synthesis. 1021 8


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