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 system involved in the reduction of 2-[4'-di(2''-bromopropyl) aminophenylazolbenzoic acid (CB10-252), an agent designed for treating primary liver cell cancer, has been demonstrated to be localised mainly in the 108 000 X g supernatant fraction of rat liver homogenate. It is also present in other organs particularly in the spleen. DAB-azoreductase as shown previously is present almost entirely in the microsomal fraction and is found in high concentration only in liver. The pH maximum for CB10-252-azoreductase implying the importance of the 2'-carboxyl group in determining substrate specificity. The use of enzyme inhibitors and other additives showed that CB10-252 WAS NOT AXANTHINE OXIDASE OR DIHYDROFOLATE REDUCTASE. Its activity was not affected by carbon monoxide, phenobarbitone (PB), or 3-methylcholanthrene (MC) pretreatment. Enhancement of the activity by ferrous ions and FAD indicated that at least part of the reduction system could involve a flavoprotein with FAD as the prosthetic group. The activity of CB10-252-azoreductase and methylred-azoreductase was reduced by menadione (vitamin K3), cyanide and propylgallate. A diaphorase preparation from pig heart reduced both CB10-252 and methylred with both NADPH- and NADH-generating systems.
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PMID:Some characteristics of two azoreductase systems in rat liver. Relevance to the activity of 2-[4'-di(2"-bromopropyl)-aminophenylazo]benzoic acid (CB10-252), a compound possessing latent cytotoxic activity. 0 Jan 49

1. Chloroplasts isolated from leaves of spinach-beet (Beta vulgaris L. ssp. vulgaris) do not catalyse the hydroxylation of p-coumaric acid in the dark unless a reductant (such as ascorbate, NADH or NADPH) is added. Superoxide dismutase has no effect on this reaction. 2. Illuminated chloroplasts catalyse the hydroxylation in the absence of added reductant. This reaction is completely inhibited by superoxide dismutase, but catalase has little effect. 3. Both hydroxylation in the light and hydroxylation in the dark in the presence of reductants are inhibited by diethyldithiocarbamate, EDTA, cyanide and 2-mercaptoethanol. 4. It is proposed that O-2- generated by illuminated chloroplasts is involved in the provision of a reductant to the enzyme phenolase.
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PMID:Hydroxylation of p-Coumaric acid by illuminated chloroplasts. The role of superoxide. 0 Feb 35

Adenine and pyridine nucleotide levels as well as those of phosphate, phosphocreatine, lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, glucose, and glycogen were measured in histologically defined parietal and mucous cell sections of biopsies of dog gastric mucosa at rest, and in various secretory states. As a result of stimulation of secretion, there appeared to be no change in adenine nucleotide levels, or phosphocreatine, but there was a rise in inorganic phosphate and a fall in phosphorylation potential. However, there was a marked increase in NADH, but no change in NADPH with onset of acid secretion. The increase in the lactate to pyruvate ratio showed that the increased NADH level occurred in the cytoplasm and these data are discussed with reference to change in cell pH.
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PMID:Metabolism of dog gastric mucosa. Nucleotide levels in parietal cells. 0 Mar 81

Treatment of submitochondrial particles (ETP) with trypsin at 0 degrees destroyed NADPH leads to NAD (or 3-acetylpyridine adenine dinucleotide, AcPyAD) transhydrogenase activity. NADH oxidase activity was unaffected; NADPH oxidase and NADH leads to AcPyAD transhydrogenase activities were diminished by less than 10%. When ETP was incubated with trypsin at 30 degrees, NADPH leads to NAD transhydrogenase activity was rapidly lost, NADPH oxidase activity was slowly destroyed, but NADH oxidase activity remained intact. The reduction pattern by NADPH, NADPH + NAD, and NADH of chromophores absorbing at 475 minus 510 nm (flavin and iron-sulfur centers) in complex I (NADH-ubiquinone reductase) or ETP treated with trypsin at 0 degrees also indicated specific destruction of transhydrogenase activity. The sensitivity of the NADPH leads to NAD transhydrogenase reaction to trypsin suggested the involvement of susceptible arginyl residues in the enzyme. Arginyl residues are considered to be positively charged binding sites for anionic substrates and ligands in many enzymes. Treatment of ETP with the specific arginine-binding reagent, butanedione, inhibited transhydrogenation from NADPH leads to NAD (or AcPyAD). It had no effect on NADH oxidation, and inhibited NADPH oxidation and NADH leads to AcPyAD transhydrogenation by only 10 to 15% even after 30 to 60 min incubation of ETP with butanedione. The inhibition of NADPH leads to NAD transhydrogenation was diminished considerably when butanedione was added to ETP in the presence of NAD or NADP. When both NAD and NADP were present, the butanedione effect was completely abolished, thus suggesting the possible presence of arginyl residues at the nucleotide binding site of the NADPH leads to NAD transhydrogenase enzyme. Under conditions that transhydrogenation from NADPH to NAD was completely inhibited by trypsin or butanedione, NADPH oxidation rate was larger than or equal to 220 nmol min-1 mg-1 ETP protein at pH 6.0 and 30 degrees. The above results establish that in the respiratory chain of beef-heart mitochondria NADH oxidation, NADPH oxidation, and NADPH leads to NAD transhydrogenation are independent reactions.
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PMID:Oxidation of NADPH by submitochondrial particles from beef heart in complete absence of transhydrogenase activity from NADPH to NAD. 0 Mar 95

The dose dependence of the acute effects of ethanol upon liver intermediary metabolism in vivo has been demonstrated in rats. Ethanol was given i.p. in doses of 0.69, 1.7, and 3.0 g/kg in equal volumes (20 ml/kg). The liver was freeze-clamped 120 min after injection, and multiple metabolites were measured in the perchloric acid extract of the tissue. Each group showed a significantly different pattern of metabolites, redox states, and phosphorylation potentials although the rate of ethanol disappearance, at least between the two highest dose groups, was not significantly different. The mitochondrial free [NAD+]/[NADH] ratios and the cytoplasmic free [NADP+]/[NADPH] ratio were paradoxically most reduced with the lowest dose of ethanol and became progressively more oxidized with increasing dose. Once established, the differences in these ratios between the groups tended to persist with time, relatively independent of the concentration of ethanol. In a somewhat different pattern, the phosphorylation potential ([ATP]/[ADP][P1]) remained at the control level in the low-dose group but was significantly elevated in the two higher-dose groups. The results, therefore, show distinct and complicated dose-dependent patterns of intermediary metabolism that cannot be explained completely by any one hypothesis but that imply significant dose-dependent effects of ethanol upon intermediary metabolism not directly related to NADH production.
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PMID:Dependence on dose of the acute effects of ethanol on liver metabolism in vivo. 0 Apr 22

Certain properties of the rat liver cell nuclei NAD-glycohydrolase (EC 3.2.2.5) were investigated. It is established that its highest activity is at 37 degrees with activation energy equal to 9480 cal/M and with factor Q10 equal to 1.5. The enzyme pH optimum in 0.2 M tris acetate is equal to 6.5 and in 0.2 potassium phosphate - 7.5. It was shown that the enzyme manifests its strict specificity only with beta-NAD, and it hardly decomposes NADP without affecting NADH, NADPH and NMN. The apparent Km value of the enzyme with respect to NAD is established. Isonicotinic acid hydrazide, nicotinamide and to the less extent nicotinic acid inhibit the enzymatic activity of nuclei. EDTA, EGTA, p-CMB, mercaptoethanol do not cause any changes in the rat liver cells nuclei NADase activity.
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PMID:[Properties of NAD-glycohydrolase of the nuclei of the liver cells of rats]. 0 Aug 30

The effect of a single interaperitoneal injection (6 mg/kg body weight) of aflatoxin B1 in propylene glycol on pyridine nucleotides and NDP linked dehydrogenases was studied 24 h after administration of the toxin. The liver showed a decrease in total proteins and pyridine nucleotides though levels of NADP and NADPH remained unchanged. Levels of NAD and NADH were decreased. The activities of hepatic of hwpRIX of hepatic malate dehydrogenase (MDH) and isocitrate dehydrogenase (ICDH) were not altered though ICDH showed an increase when expressed on protein basis. However, there was a significance decrease in the activity of combined HMP dehydrogenases. Adipose tissue showed increased activities of the HMP dehydrogenasess.
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PMID:Effect of aflatoxin B1 on pyridine nucleotides and NADP linked dehydrogenases. 0 75

Re-investigating the accuracy of the commonly used values for molar absorptivities (epsilon) of beta-NADH and beta-NADPH at Hg 334, Hg 365, or 340 nm, we obtained the following results: The maximum of absorbance of NADH is shifted from about 340 nm at 0 degrees C to about 338.5 nm at 38 degrees C; the corresponding maxima of NADPH are located at about 0.5-nm longer wavelengths. In addition, the absorption curves of both coenzymes broaden with increasing temperature. For these reasons, the epsilon-values of NADH and NADPH are generally different from each other, and are temperature-dependent. Only at 334 nm are they almost identical and nearly independent of temperature. Therefore this wavelength is recommended for precise measurements. The epsilon-values of these coenzymes are influenced by ionic strength and pH. To determine the absolute values of the molar absorptivities, we performed the glutamate dehydrogenase or lactate dehydrogenase assay with carefully purified 2-oxoglutaric acid or pyruvic acid in the presence of excess coenzyme. The purity of the substrates was checked through differential scanning calorimetry, moisture analysis, gas-liquid chromatography, gas chromatography in combination with mass spectrometry, and nuclear magnetic resonance spectroscopy. The epsilon-values observed under the various conditions are about 1-7% higher than those currently used.
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PMID:Molar absorptivities of beta-NADH and beta-NADPH. 0 89

In rat liver cells isolated by perfusion in the perfusion in the presence of collagenase, the major portion of cytochrome P-450 is present in the oxidized, nonsubstrate-bound, low spin state. Drug addition to a suspension of liver cells results in the rapid formation of the cytochrome P-450 (Fe3+)-substrate complex which in turn is followed by the appearance of other species with different spectral characteristics before steady state drug monooxygenation is achieved. Cytochrome P-450-linked metabolism of various tested drugs and carcinogenic polycyclic hydrocarbons by isolated rat liver cells is as fast, or faster, as with rat liver microsomes supplemented with a NADPH generating system. Both experimental models respond similarily to phenobarbital or 3-methylcholanthrene pretreatment of the animals and to various of the wellknown inhibitors of drug metabolism. Except with liver cells isolated from fasted, phenobarbital-treated rats, generation of cytosolic NADPH seems sufficient to support optimal drug metabolism even in the absence of added substrates of intermediary metabolism. In isolated liver cells oxidized drug metabolites undergo subsequent metabolic conversion, most often to form the corresponding glucuronides and sulphates. These are readily excreted, whereas non-conjugated products, e.g. free phenols, tend to accumulate intracellularly. Cellular glucuronide formation is strongly inhibited by ethanol-presumably due to an unfavorable effect of the increased NADH/NAD+ ratio on the synthesis of uridine-5'-diphosphoglucuronic acid (UDPGA). In contrast, low concentrations of ethanol have no, or only a slight stimulatory effect on the cytochrome P-450-linked step of drug metabolism and there are indications that the oxidation of low concentrations of ethanol is in fact stimulated by a facilitated reoxidation of cytosolic NADH occuring during drug monooxygenation.
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PMID:Recent studies on cytochrome P-450-linked functions in isolated rat liver cells. 0 26

The microsomal 3-hydroxysteroid dehydrogenases were solubilized with lubrol, a non-ionic detergent. A 3alpha-hydroxysteroid dehydrogenase is purified about 100-fold by double affinity chromatography on 5alpha-dihydrotestosterone-Sepharose. This enzyme can use both NADH and NADPH as coenzymes.
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PMID:[Solubilization and purification of a 3alpha-hydroxysteroid dehydrogenase in rat liver microsomes (author's transl)]. 0 35


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