Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effect of 1-(m-chlorphenyl)-3-N,N-dimethylcarbamoyl-5-methoxypyrazole (PZ-177) (62.5 and 250 mg/kg) on rat liver was investigated by measuring liver weight and drug-metabolizing enzyme activity. The effects of PZ-177 were compared with those of phenobarbital, phenylbutazone, and tiaramide hydrochloride. Increase of liver weight and liver/body weight ratio was observed in the rats treated with PZ-177 or phenobarbital, however, normal values were reverted to 1--2 weeks after treatment. PZ-177 similar to phenobarbital, significantly enhanced the activity of aminopyrine demethylase and aniline hydroxylase after 1,2, and 4 weeks of treatment. In contrast, tiaramide hydrochloride decreased the activity of aminopyrine demethylase and aniline hydroxylase after 1 week of treatment, and significantly enhanced the activity of these enzymes after 4 weeks. The content of cytochrome P-450 and the activity of NADPH cytochrome C reductase were also increased by treatment with PZ-177. The sleeping time by hexobarbital was shortened significantly by the administration of PZ-177. Vmax for both aminopyrine demethylase and aniline hydroxylase increased by treatment with PZ-177. However, only the Km for aniline hydroxylase was increased by treatment with PZ-177. From the results of these experiments, PZ-177 may be classified as a phenobarbital-type inducer.
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PMID:Effect of 1-(m-chlorophenyl)-3-N,N-dimethyl-carbamoyl-5-methoxypyrazole (PZ-177) on drug-metabolizing enzyme on rat liver. 108 57

The absence of correlation between the effect of aniline and aminoantipyrine derivatives on cytochrome P-450 reduction rate and its oxidation rate draw to the conclusion that the reductase reaction is not a limiting step of hydroxylation for all substrates. Km is found to be directly proportional to Vmax of hydroxylated substrates. Hence, in these reactions the Km value is determined not by the value Ks but by the kappa+2/kappa+1 ratio. Km is not a characteristic of the affinity of cytochrome P-450 to substrates. The calculations were made to show that cytochrome P-450 formed two types of the enzyme-substrate complexes containing one or two substrate molecules. The complex in which one molecule of cytochrome P-450 binds one substrate molecule is considered to be active.
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PMID:[Hydroxylation of aniline and aminoantipyrine derivatives (1-phenyl-2,3-dimethylaminopyrazolon-5) in liver endoplasmic reticulum]. 113 1

The reduction of highly purified cytochrome P-450 from rabbit liver microsomes under anaerobic conditions requires 2 electrons per molecule. Similar results were obtained with dithionite, NADPH in the presence of NADPH-cytochrome P-450 reductase, or a photochemical system as the electron donor, with CO or other ligands, with substrate or phosphatidylcholine present, after denaturation to form cytochrome P-420, or with cytochrome P-450 partially purified from rat or mouse liver microsomes. The reduced cytochrome P-450 donates 2 electrons to dichlorophenolindophenol or to cytochrome c. Reoxidation of reduced cytochrome P-450 by molecular oxygen restores a state where 2 electrons from dithionite are required for re-reduction. Although these unexpected findings indicate the presence of an electron acceptor in addition to the heme iron atom, significant amounts of non-heme iron, other metals or cofactors, or disulfide bonds were not found, and free radicals were not detected by electron paramagnetic resonance spectrometry. Resolution of the cytochrome with acetone and acid yielded the apoenzyme, which did not accept electrons, and ferriprotoporphyrin IX, which accepted a single electron. A reconstituted hemoprotein preparation with the spectral characteristics of cytochrome P-420 accepted as much as 0.7 extra electron equivalent per heme. The midpoint oxidation-reduction potential of purified cytochrome P-450 from rabbit liver microsomes at pH 7.0 is -330 mv, and with CO present this value is changed to about -150 mv. The oxidation-reduction potential is unaffected by the presence of phosphatidylcholine or benzphetamine, a typical substrate. Laurate, aminopyrine, and benzphetamine undergo hydroxylation in the presence of chemically reduced cytochrome P-450 and molecular oxygen. Neither NADPH nor the reductase is required for substrate hydroxylation under these conditions.
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PMID:Purified liver microsomal cytochrome P-450. Electron-accepting properties and oxidation-reduction potential. 116 47

1. Liver microsomal preparations from chick embryos (1 day before hatching) and from 1-7 day old chicks were assayed for oxidative drug-metabolizing activity with aminopyrine, aniline and naphthalene as substrates. 2. Activities for all three substrates were highest in preparations from 1 day-old chicks. These were more than twice as active as the 7 day-old preparations and about three times as active as those from the embryos. 3. The increase in drug-metabolizing activities in newly-hatched chicks was the same for either sex and persisted for 3 days before declining towards the 7 day-old levels. 4. The developmental time-course fo the liver microsomal drug-metabolizing activities was independent of any factor in the 105 000 g supernatant fractions and of such microsomal parameters as cytochrome b5 and cytochrome P-450 content, and NADPH-cytochrome c reductase activity, but was related to changes in NADPH-cytochrome P-450 reductase levels. 5. Treatment of 7 day-old chicks with exogenous inducers, 3-methylcholanthrene or phenobarbital sodium (100 mg/kg, intraperitoneally) brought about maximal stimulation of microsomal activity as 18-24 h. The time-course of this induction was reflected by changes in microsomal cytochrome P-450 content and NADPH-cytochrome P=450 reductase activities. 6. Some induction of liver microsomal drug metabolism in 7 day-old chicks could also be brought about by injecting certain lipid-soluble egg yolk extracts.
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PMID:Development of liver microsomal oxidations in the chick. 127 75

Circadian changes in cytochrome P-450 and cytochrome b5 content and activity of NADPH-cytochrome P-450 and NADH-cytochrome b5 reductases have been studied in rat liver microsomes in season autumn. The obtained results indicate, that cytochrome P-450 in 6-month-old animals shows 12 h rhythm, but in older ones 24 h rhythm. NADPH-cytochrome P-450 reductase activity shows 24 h rhythm in oldest animals only. Cytochrome b5 and its reductase has 24 h rhythm in all examined groups of rats.
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PMID:Circadian changes of cytochrome P-450-dependent monooxygenase system in the rat liver. 130 61

Intoxication of male and female mice with a single dose (300 or 600 mg/kg) of 1,1,2,2-tetrachloroethane (TTCE) resulted in significant decreases in cytochrome P-450 (to 58-73% of the control) and NADPH-cytochrome (P-450) c-reductase (to 29-35% of the control) in hepatic microsomes. This was accompanied by an alteration of mixed function monooxygenases stemming from the marked reduction (to 20-64% of the control) of several oxidative activities to selected substrates towards different P-450 isozymes (classes IA1, IA2, IIB1, IIE1 and IIIA). As phase II markers, epoxide hydrolase (approximately 35% loss), UDP-glucuronosyl transferase (approximately 42% loss) and to a lesser extent glutathione S-transferase (approximately 17% loss) were all affected. Also, the activity of delta-aminolevulinic (ALA) synthetase was decreased (approximately 57% of the control). On the contrary, heme oxygenase activity was increased (up to 35%) at the maximal dose tested. The decrease of P-450-function may be explained in terms of an alteration in the rate of heme biosynthesis and degradation, provoking a loss of heme content (approximately 33%) as well as of the direct inactivation of both P-450 and reductase. Because of increasing evidence on the involvement of free radical intermediates in the case of toxicity of haloalkanes, electron spin resonance spectroscopy (ESR) spin-trapping in vivo techniques were used to characterize the possible free radical species involved in the observed liver damage. The results obtained with the spin-trap N-benzylidene-2-methylpropylamine N-oxide (phenyl t-butylnitrone, PBN) provide evidence for the formation and trapping of the CHCl2CHCl free radicals. The detection of conjugated diene signals by means of second-derivative spectrophotometry, have enabled us to show that in vivo lipid peroxidation may be one of the main mechanisms responsible for TTCE hepatotoxicity.
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PMID:On the hepatotoxicity of 1,1,2,2-tetrachloroethane. 131 68

Effect of age and phenobarbital on the rat mixed function oxidase activity was studied. Male Wistar rats 0.5-, 1-, 2-, 4-, 8-, 12-, 20- and 28 month-old were used. In this study the levels of cytochrome P-450 and cytochrome b5. NADPH-cytochrome P-450 and NADH-cytochrome b5 reductases activity were examined. Both cytochrome P-450 and NADPH-cytochrome P-450 reductase activity was induced by phenobarbital in all animals. Maximum was observed in 4- and 8-month-old for hemoprotein and 2-month-old rats for reductase activity but minimum in youngest and oldest one respectively. On the contrary, cytochrome b5 and NADH-cytochrome b5 reductase activity was inhibited after phenobarbital injection. The highest depression of cytochrome b5 content was found in youngest, but the enzyme activity in oldest rats.
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PMID:[Effect of age and phenobarbital on liver activity of mixed function oxidase]. 134 96

Oxidative metabolism of delta 9-tetrahydrocannabinol (THC) by liver microsomes was studied in female rats. Delta 9-THC was mainly biotransformed to 11-hydroxy-delta 9-THC (11-OH-delta 9-THC) and 9 alpha,10 alpha-epoxy-hexahydrocannabinol (EHHC) by liver microsomal fraction of adult female rat. Two isozymes of cytochrome P-450 (P-450) [F-1 (IIC6) and F-2 (IIC12)] were purified from liver microsomes of female rats and oxidation activities toward delta 9-THC were assessed in the reconstituted system containing NADH-P-450 reductase and cytochrome b5. P-450 F-1 showed considerable activity toward 11-OH-delta 9-THC formation (10.62 nmol/min/nmol of P-450), whereas P-450 F-2 did not show any activity toward delta 9-THC oxidation under the conditions used. Preincubation of microsomes with antiserum against P-450 F-1 obtained from rabbits caused a marked decrease in 11-OH-delta 9-THC formation, whereas antiserum against P-450 F-2 did not exhibit any inhibitory effect on the oxidation of delta 9-THC by liver microsomes of adult female rats. Further, antiserum against P-450 F-1 or F-2 did not affect the microsomal formation of 9 alpha,10 alpha-EHHC from delta 9-THC. These results indicate that P-450 F-1 and its immunochemically related P-450 isozyme(s) play important roles in the formation of an active metabolite, 11-OH-delta 9-THC, from delta 9-THC by liver microsomes of adult female rats.
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PMID:Cytochrome P-450 isozymes involved in the oxidative metabolism of delta 9-tetrahydrocannabinol by liver microsomes of adult female rats. 134 1

Nitric oxide has emerged as an important mammalian metabolic intermediate involved in critical physiological functions such as vasodilation, neuronal transmission, and cytostasis. Nitric oxide synthase (NOS) catalyzes the five-electron oxidation of L-arginine to citrulline and nitric oxide. Cosubstrates for the reaction include molecular oxygen and NADPH. In addition, there is a requirement for tetrahydrobiopterin. NOS also contains the coenzymes FAD and FMN and demonstrates significant amino acid sequence homology to NADPH-cytochrome P-450 reductase. Herein we report the identification of the inducible macrophage NOS as a cytochrome P-450 type hemoprotein. The pyridine hemochrome assay showed that the NOS contained a bound protoporphyrin IX heme. The reduced carbon monoxide binding spectrum shows an absorption maximum at 447 nm indicative of a cytochrome P-450 hemoprotein. A mixture of carbon monoxide and oxygen (80%/20%) potently inhibited the reaction (73-79%), showing that the heme functions directly in the oxidative conversion of L-arginine to nitric oxide and citrulline. Additionally, partially purified NOS from rat cerebellum was inhibited by CO, suggesting that this isoform may also contain a P-450-type heme. NOS is the first example of a soluble cytochrome P-450 in eukaryotes. In addition, the presence of FAD and FMN indicates that this is the first catalytically self-sufficient mammalian P-450 enzyme, containing both a reductase and a heme domain on the same polypeptide.
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PMID:Nitric oxide synthase is a cytochrome P-450 type hemoprotein. 137 68

The intrauterine position of rat fetuses between siblings of the same or opposite sex has been reported to alter sexually dimorphic behavioral and reproductive traits in the adult. The intrauterine fetal position of adult rats is identified by a three letter code as mMm (a male, M, located between two male siblings, m-m) and fFf (a female, F, positioned between two females, f-f). This study sought to determine whether intrauterine location affected the hepatic polysubstrate monooxygenase and glutathione S-transferase activity, plasma sex steroid levels and organ weights in adult Long-Evans rats. The hepatic microsomal cytochrome P-450 content was higher in females located in utero between two male littermates (mFm) than in females positioned between two females (fFf). NADPH cytochrome c reductase activity was higher in mMm males (positioned in utero between two males) than in fMf males (males contiguous to two female littermates) and female rats. Hepatic microsomal testosterone 2 alpha- and 6 beta-hydroxylase activity was undetectable in fFf female but both activities were measurable in mFm female rats. Testosterone 7 alpha-hydroxylase and 5 alpha-reductase activity was higher in females than in males, and higher in fFf than in mFm females. Glutathione S-transferase activity was not altered by fetal contiguity in male and female rats. Adult mMm males had a higher plasma testosterone level and relative gonadal weight, and lower plasma estradiol concentration than fMf males. The plasma progesterone concentration of fFf female was lower than that of mFm female rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of intrauterine position on the hepatic microsomal polysubstrate monooxygenase and cytosolic glutathione S-transferase activity, plasma sex steroids and relative organ weights in adult male and female Long-Evans rats. 140 93


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