Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The epoxide hydrase assay developed by Oesch et al. (Biochim. Biophys. Acta, 227: 685-691, 1971) using [3H]styrene oxide as substrate was modified in three ways for use with rat lung microsomes: the substrate was purified before use, the volume of the incubation mixture was scaled down 4-fold, and the incubation time was extended to 45 min (activity was found to be linear for at least 60 min). These modifications increased the sensitivity of the assay procedure 75- to 150-fold. The procedure was found to be linear with lung microsomal protein up to at least 1.8 mg protein per incubation mixture. This modified assay for epoxide hydrase was used to characterize the enzyme in rat lung. Its apparent vmax is 0.5 nmole of styrene glycol formed per min per mg microsomal protein, and its apparent Km was 0.11 to 0.25 mM. The pH optimum is around 9.7. Upon subcellular fractionation of lung tissue, expoxide hydrase distributes in the same manner as a marker for the endoplasmic reticulum (reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase) and in a different way from markers for the nuclei, mitochondria, concentric lamellar organelles, lysosomes, Golgi membranes, plasma membrane and soluble cytoplasm. The specific activity of epoxide hydrase in rough and smooth lung microsomes is aobut the same. Treatment i.p. of rats with methylcholanthrene (3 injections of 20 mg/kg), phenobarbital (5 daily injections of 80 mg/kg) or styrene oxide (5 daily injections of 40 mg/kg), did not induce lung microsomal epoxide hydrase activity. 1,1,1-Trichloropropene 2,3-oxide was shown to be an uncompetitive inhibitor, and cyclohexene oxide was a noncompetitive inhibitor of this enzyme. Ethanol and butanol activate the epoxide hydrase of lung microsomes at low concentrations and inhibit it at higher concentrations.
 ...
PMID:Characterization of rat lung epoxide (styrene oxide) hydrase with a modified radioactive assay of improved sensitivity. 40 99

Hexobarbital was given to anaesthetized mice for a period of 7 h by repeated i. p. injection, first of 100 mg/kg,then several times of 50 mg/kg. A high level of hexobarbital was maintained in the liver. The activity of microsomal drug-metabolizing enzymes was induced by this treatment with hexobarbital. 30 min after a single i. p. injection of 100 mg/kg of hexobarbital, there was a significant inhibition of aminopyrine N-demethylase but none of cytochrome c and neotetrazolium reductases. Hexobarbital in vitro inhibits aminopyrine N-demethylase but not cytochrome c reductase.
 ...
PMID:Induction of microsomal drug-metabolizing enzymes caused by hexobarbital. 41 31

Elaidic and linoleic acids were administered at doses of 40 and 200 mg/kg i.p. every second day for 4 weeks to rats fed a fat-free diet. The fatty acids had only a slight effect on the weight gain of the animals. The amount of microsomal protein was slightly decreased with the higher dose of linoleic acid. The higher dose level of both fatty acids decreased the microsomal phospholipid content. The relative amounts of microsomal phospholipid fatty acids were also altered due to fatty acid administration. The activity of microsomal NADPH cytochrome c reductase and microsomal cytochrome P-450 contents were decreased by the higher dose of linoleic acid. The hepatic aryl hydrocarbon hydroxylase and p-nitroanisole O-demethylase activities decreased in fatty acid-treated rats. The UDP-glucuronosyltransferase activity was also lowered after the fatty acid administration. The results suggest that fatty acid-induced changes in the activities of drug-metabolizing enzymes may be due to the microenvironmental changes of membrane-bound enzymes.
 ...
PMID:Regulation of hepatic drug metabolism by elaidic and linoleic acids in rats. 41 54

Two subcellular fraction, P-1 and P-2, were isolated by differential centrifugation from 0.25 M sucrose muscle homogenates of the parasitic roundworm, Ascaris lumbricoides suum. Morphological studies indicated that P-1 fraction consisted of intact mitochondria, whereas P-2 fraction consisted almost exclusively of vesicular components. The difference spectrum of Ascaris microsomes showed a characteristic b-type cytochrome spectrum with three distinct absorption peaks at 560, 525, and 424 nm. However, the alpha-peak at 560 nm was asymmetric with a shoulder at 555 nm. This microsomal b-type cytochrome was reduced by NADH, which was inhibited by rotenone and HgCl2. The reduced b-type cytochrome was easily reoxidized by shaking. NADH-oxidase activity observed in Ascaris microsomes was inhibited by rotenone, but not by KCN, NaN3, and antimycin A. On the other hand, NADH-cytochrome c and NADH-neotetrazolium (NT) reductase activities in Ascaris microsomes were not inhibited by antimycin A and rotenone, but were inhibited by HgCl2. Further observations indicated that neither HgCl2 nor rotenone inhibited Ascaris microsomal NADH-ferricyanide (FC) reductase activity, but rabbit antibody prepared against the purified NADH-FC reductase inhibited the NADH-cytochrome c reductase activity, the reduction of b-type cytochrome and the NADH-oxidase activity, as well as microsomal NADH-FC reductase activity.
 ...
PMID:Biochemical studies on the muscle microsomes of Ascaris lumbricoides var. suum. I. Biochemical characterization and electron transport of Ascaris microsomes. 42 35

Thiourea and diethylthiourea, two compounds which react with hydroxyl radicals, inhibited NADPH-dependent microsomal oxidation of ethanol and 1-butanol. Inhibition by both compounds was more effective in the presence of the catalase inhibitor, azide. Inhibition by thiourea was noncompetitive with respect to ethanol in the absence of azide but was competitive in the presence of azide. Urea, a compound which does not react with hydroxyl radicals or H2O2, was without effect. Thiourea had no effect on NADH- and NADH-cytochrome c reductase, NADPH oxidase, and NADH- and NADPH-dependent oxygen uptake. Thiourea inhibited the activities of aniline hydroxylase and aminopyrine demethylase. Thiourea, but no other hydroxyl radical scavengers, e.g., dimethyl sulfoxide, mannitol, and benzoate, reacted directly with H202 and decreased H2O2 accumulation in the presence of azide. Therefore the actions of thiourea are complex because it can react with both hydroxyl radicals and H2O2. Differences between the actions of thiourea and those previously reported for dimethyl sulfoxide, mannitol, and benzoate, e.g., effects on drug metabolism, effectiveness of inhibition in the absence of azide, or kinetics of the inhibition, probably reflect the fact that thiourea reacts directly with H2O2 whereas the other agents do not. The current results remain consistent with the concept that microsomal oxidation of alcohols involves interactions of the alcohols with hydroxyl radicals generated from microsomal electron transfer.
 ...
PMID:Effect of thiourea on microsomal oxidation of alcohols and associated microsomal functions. 42 8

Cadmium is a potent inhibitor of hepatic microsomal drug biotransformation in the rat. Male rats receiving a single intraperitoneal dose of cadmium exhibit significant decreases in hepatic microsomal metabolism of a variety of substrates. The threshold cadmium dose is 0.84 mg Cd/kg, and the effect lasts at least 28 days. Mechanistically, the inhibitory effect results from decreased cytochrome P-450 content since cadmium does not alter NADPH cytochrome c reductase activity. This effect is also observed following acute oral administration of cadmium in doses greater than 80 mg Cd/kg but is not observed following chronic administration of the metal via drinking water in concentrations of 5-200 ppm for periods ranging from 2 to 50 weeks. A tolerance to the inhibitory cadmium effect is observed if male rats are pretreated with subthreshold doses of the metal prior to the challenge cadmium dose. The degree of tolerance can be overcome by increasing the challenge dose of cadmium. Characterization of the tolerance phenomenon in terms of onset, duration, and intensity reveals a good correlation with the kinetics of metallothionein production, suggesting that the underlying basis for the tolerance phenomenon is likely the induction of metallothionein. A sex-related difference in the inhibitory effect of cadmium was observed. Cadmium did not inhibit the metabolism of hexobarbital or ethylmorphine in female rats but did inhibit that of aniline or zoxazolamine. Cadmium did not lower cytochrome P-450 content in female rats.
 ...
PMID:Studies on cadmium-induced inhibition of hepatic microsomal drug biotransformation in the rat. 48 42

The electrophilic properties of the quinone-hydroquinone configuration of anthracycline antibiotics suggests a possible influence on cytochrome P-450-mediated mono-oxygenase reactions. Both doxorubicin and triferric-doxorubicin (a derivative in which the quinone groups are blocked with iron) showed a similar dose-dependent inhibition of liver microsomal drug metabolism. A doxorubicin concentration-related stimulation of NADPH oxidase activity was found to be linear but that for triferric-doxorubicin was asymptotic. Neither inhibitor affected the activity of cytochrome c reductase, cytochrome b5 reductase or cytochrome P-450 reductase. However, doxorubicin did potentiate the inhibitory effect of aniline on cytochrome P-450 reductase and on ethylmorphine metabolism. It is concluded that these anthracyclines inhibit drug metabolism in vitro not by their electron-withdrawing potential but in a manner more similar to that described for type II compounds.
 ...
PMID:Inhibition of drug oxidation and stimulation of NADPH oxidase in vitro by doxorubicin and triferric-doxorubicin. 51 68

Hexachlorobenzene, which is a widespread contaminant of meat and meat animal by-products throughout the world, had a profound effect on the homeostatic mechanism which controls the serum testosterone concentrations in the mouse. Significant increases in the mean hepatic weight, the concentrations of hepatic microsomal protein, cytochrome P-450, cytochrome b5, and cytochrome c reductase activity occurred in the aminals given a ration containing 250 mg of hexachlorobenzene/kg for 21 days, when compared with their nontreated controls. These increases in cytochrome concentrations and enzyme activity of the hepatic microsomes are reflected by significant increases in the in vitro metabolism of [3H]testosterone and a decrease in the serum concentrations of testosterone with a concomitant decrease in the weights of the seminal vesicles and ventral prostate of the mouse.
 ...
PMID:Testosterone metabolism by hexachlorobenzene-induced hepatic microsomal enzymes. 52 97

The greater part of T3 is converted from T4 in liver or kidney. The majority of this activity exists in microsomal fraction. In the present study, we investigated whether this activity can be solubilized from rat liver microsomal pellet with various concentrations of deoxycholate (DOC). The extent of solubilization was compared with that of protein, rotenone insensitive NADH cytochrome c reductase or NADH cytochrome b5 reductase, which have been shown to associate with microsomal membrane rather than luminar contents. When 0.05% of DOC which was capable of releasing luminar contents of microsomal vesicles was applied to microsomal suspension, only a limited part of NADH cytochrome b5 reductase, rotenone insensitive NADH cytochrome c reductase or T4-5'-deiodinase activity was solubilized. When the concentration of DOC was increased to 0.125%, 41% of T4-5'-deiodinase activity was solubilized. Solubilization of protein, NADH cytochrome b5 reductase or rotenone insensitive NADH cytochrome c reductase was increased abruptly to 66%, 58% or 63%, respectively. The highest specific activity was obtained at 0.125% DOC. These results suggest that the T4-5'-deiodinase is associated with microsomal membrane instead of luminar contents.
 ...
PMID:Solubilization of thyroxine-5'-deiodinase activity from rat liver microsome fraction. 53 25

S-Adenosyl-L-methionine (SAMe) levels in liver tissue were reduced by 35% after isolation and washing of the organ. The apparent half-life of SAMe (1,75-25 microM) during liver perfusion was between 120 and 460 min; however the uptake of the labelled methyl group by hepatic tissue of fed rats was low (6%). This value increased to 12% in organs isolated from 24-hour fasted animals. Addition of SAMe to the perfusion medium increased tissue levels of ATP. Except for N-demethylation of aminopyrine and cytochrome c reductase, liver microsomal activity was not affected by treatment with SAMe either in vivo or/and in perfused liver.
 ...
PMID:Kinetics of S-adenosyl-L-methionine in isolated perfused rat liver and its effects on microsomal enzyme activity. 53 98


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>