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)

The effects of antibodies to cytochromes P-45017 alpha,lyase and P-450C21 on benzo[a]pyrene hydroxylase activity were measured in microsomes from guinea pig adrenals. Anti-cytochrome P-45017 alpha,lyase IgG inhibited about 30% of the benzo[a]pyrene hydroxylase activity of the microsomes in the presence of excess amounts of the IgG, but anti-cytochrome P-450C21 IgG did not affect the activity. In a reconstituted system, consisting of cytochrome P-450, NADPH-cytochrome-P-450 reductase and dilauroylphosphatidylcholine, cytochrome P-45017 alpha,lyase catalyzed, in addition to steroid hydroxylation, benzo[a]pyrene hydroxylation, but cytochrome P-450C21 did not hydroxylate benzo[a]pyrene. Since anti-cytochrome P-45017 alpha,lyase IgG inhibited benzo[a]pyrene hydroxylase activity completely in the reconstituted system with cytochrome P-45017 alpha,lyase, the presence of non-inhibited benzo[a]pyrene hydroxylase in the microsomes suggests that the residual activity in the microsomes may be due to some enzyme other than cytochrome P-45017 alpha,lyase. Benzo[a]pyrene hydroxylase activity was detected in detergent-solubilized microsomes from which cytochrome P-45017 alpha,lyase was removed by using an immobilized anti-cytochrome P-45017 alpha,lyase IgG-Sepharose column. This shows the existence in microsomes of a benzo[a]pyrene hydroxylase other than cytochrome P-45017 alpha,lyase. Benzo[a]pyrene hydroxylase in the solubilized microsomes required O2, NADPH and NADPH-cytochrome-P-450 reductase for its activity and was inhibited by CO. This suggests that benzo[a]pyrene hydroxylase is a cytochrome P-450-dependent monooxygenase. This novel enzyme was also active in xenobiotic metabolism, such as 2-nitropropane denitrification and aminopyrine demethylation.
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PMID:Examination of differences between benzo[a]pyrene and steroid hydroxylases in guinea pig adrenal microsomes. 333 76

Cellular immunity and activity of enzymes of xenobiotic metabolism have been investigated. It has been shown that administration of benzene induces a stable immune deficiency syndrome characterized by a decrease in the quantity if antibody-forming cells, T-killers and T-suppressors. The activity of enzymes (cytochrome P-450 and cytochrome C reductase) was also inhibited. It has been shown that anabol can stimulate the parameters of cellular immunity and enzyme activity. Benzene intoxication was demonstrated to be a model of immune deficiency syndrome similar to the clinical pattern. Anabol was shown to be an effective immunomodulator.
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PMID:[Induction of immunologic deficiency by benzene and its correction by administration of anabol]. 335 30

Through the use of drug-adapted tissue culture cells, correlations have been observed between the level of specific enzymes and drug resistance. Drug resistance, however, may be due to multiple factors. To test whether the activity of daunorubicin reductase or NADPH diaphorase independently influences in vitro daunorubicin-induced cytotoxicity, we developed somatic cell hybrid clones to partially isolate these factors. This was accomplished by fusing daunorubicin-resistant myeloblast cells obtained from a patient with monosomy 7 leukemia to a daunorubicin-sensitive Chinese hamster cell line. The in vitro cytotoxicity of daunorubicin was compared in hybrid clones having variable enzyme activities; the concentrations of daunorubicin that inhibited the growth of clones by 50% did not differ by more than 2-fold, whereas daunorubicin reductase activities and NADPH diaphorase isozyme activities differed by more than 100- and 15-fold, respectively. These large differences in enzymatic activity were obtained in part by the suppression of specific hamster genes, indicating a regulatory control mechanism for xenobiotic enzymes. Our findings suggest that in this system substantial intercellular variation in the activity of these xenobiotic enzymes does not independently influence cellular resistance to daunorubicin.
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PMID:Use of somatic cell hybrids to analyze role of specific enzymes in daunorubicin cytotoxicity. 354 57

NADP+-dependent dihydrodiol dehydrogenase (trans-1,2-dihydrobenzene-1,2-diol: NADP+ oxidoreductase, EC 1.3.1.20) activity in the cytosol of guinea-pig testis was separated into two major and two minor peaks by Q-Sepharose chromatography; one minor form was immunologically cross-reacted with hepatic aldehyde reductase. The two major enzyme forms were purified to homogeneity. One form, which had the highest amount in the tissue, was a monomeric protein with a molecular weight of 32,000 and isoelectric point of 4.2, showed strict specificity for benzene dihydrodiol and NADP+, and reduced pyridine aldehydes, glyceraldehyde and diacetyl at low rates. Another form, with a molecular weight of 36,000 and isoelectric point of 5.0, oxidized n-butanol, glycerol and sorbitol as well as benzene dihydrodiol in the presence of NADP+ or NAD+, and exhibited much higher reductase activity towards various aldehydes, aldoses and diacetyl. The pI 5.0 form was more sensitive to inhibition by sorbinil and p-chloromercuriphenyl sulfonate than the pI 4.2 form and was activated by sulfate ion. The two enzymes did not catalyze the oxidation of hydroxysteroids and xenobiotic alicyclic alcohols and were immunologically different from hepatic 17 beta-hydroxysteroid-dihydrodiol dehydrogenase. The results indicate that guinea-pig testis contains at least two dihydrodiol dehydrogenases distinct from the hepatic enzymes, one of which, the pI 5.0 enzyme form, may be identical to aldose reductase.
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PMID:Purification and properties of two multiple forms of dihydrodiol dehydrogenase from guinea-pig testis. 354 26

Employing reconstitution assays and measurement of cytochrome P-450 content, lanosterol 14 alpha-demethylase and cholesterol 7 alpha-hydroxylase have been studied in solubilized preparations of rat hepatic microsomes. Both activities have been resolved from other cytochrome P-450 isozymes and each other by chromatography on DEAE-Sephacel and adsorption on hydroxylapatite. The demethylase has been further purified to homogeneity by cation exchange chromatography on Mono-S resin. The purified cytochrome displays a specific content of 15.8 nmol of heme/mg of protein and a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent Mr of 51,000. A Soret maximum for the reduced/CO binding complex at 448 nm is observed. Reconstitution of the purified cytochrome with NADPH-cytochrome-c reductase, dilaurylphosphatidylcholine, NADPH, and O2 supports the demethylation process which is inhibited by CO. Reconstitution also affords accumulation of oxygenated, metabolic intermediates with single catalytic turnover of the cytochrome, thus supporting the hypothesis that a single isozyme of cytochrome P-450 is responsible for all three oxidations and the lyase activity involved in the lanosterol C-32 demethylation sequence. Low oxidase activity toward several xenobiotic substrates and selectivity toward endogenous sterol substrates is observed for the purified cytochrome. These results indicate a high degree of substrate specificity for the cytochrome, which would be expected for a constitutive P-450 involved in anabolic biochemical processes.
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PMID:Microsomal enzymes of cholesterol biosynthesis. Purification of lanosterol 14 alpha-methyl demethylase cytochrome P-450 from hepatic microsomes. 377 45

The data on the activity of the enzymes of xenobiotic metabolism in peripheral blood lymphocytes point to essential disorders within the system of detoxification in patients with bronchopulmonary pathology. The necessity of cultivating cells with mitogens before measurement of the activity of the enzymes of xenobiotic metabolism of the first phase (cytochrome P-450, cytochrome C-reductase) for more precise measurement and reproducibility of the results is discussed. Study of the activity of cytosol enzymes of the second phase (glutathione-S-transferase, sulfotransferase) does not require preliminary cell cultivation. The authors emphasize the importance of studying the enzymes of xenobiotic metabolism to individualize the treatment and choose optimal drug doses.
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PMID:[The enzyme spectrum of the peripheral blood lymphocytes in patients with nonspecific lung diseases]. 385 47

Four NADPH-dependent aldehyde reductases (ALRs) isolated from pig brain have been characterized with respect to substrate specificity, inhibition by drugs, and immunological criteria. The major enzyme, ALR1, is identical in these respects with the high-Km aldehyde reductase, glucuronate reductase, and tissue-specific, e.g., pig kidney aldehyde reductase. A second enzyme, ALR2, is identical with the low-Km aldehyde reductase and aldose reductase. The third enzyme, ALR3, is carbonyl reductase and has several features in common with prostaglandin-9-ketoreductase and xenobiotic ketoreductase. The fourth enzyme, unlike the other three which are monomeric, is a dimeric succinic semialdehyde reductase. All four of these enzymes are capable of reducing aldehydes derived from the biogenic amines. However, from a consideration of their substrate specificities and the relevant Km and Vmax values, it is likely that it is ALR2 which plays a primary role in biogenic aldehyde metabolism. Both ALR1 and ALR2 may be involved in the reduction of isocorticosteroids. Despite its capacity to reduce ketones, ALR3 is primarily an aldehyde reductase, but clues as to its physiological role in brain cannot be discerned from its substrate specificity. The capacity of succinic semialdehyde reductase to reduce succinic semialdehyde better than any other substrate shows that this reductase is aptly named and suggests that its primary role is the maintenance in brain of physiological levels of gamma-hydroxybutyrate.
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PMID:Identification of pig brain aldehyde reductases with the high-Km aldehyde reductase, the low-Km aldehyde reductase and aldose reductase, carbonyl reductase, and succinic semialdehyde reductase. 388 45

Components of little skate (an elasmobranch) and rabbit hepatic microsomal cytochrome P-450 dependent monooxygenase systems were examined for differences which might explain the decreasing xenobiotic-metabolizing activity of little skate microsomes assayed at temperatures above 30 degrees C. The proportion of saturated fatty acids in microsomal lipids and the habitat temperature are both lower in skate as compared to rabbit, which is consistent with the known adaptive pattern. The more thermolabile enzyme of the skate system in microsomal preparations is NADPH-cytochrome P-450 reductase. The optimal assay temperature for purified skate reductase (30 degrees C) is 10 degrees C lower than that for the purified rabbit reductase. The purified skate reductase differs from rabbit reductase in monomeric molecular weight, in peptides produced by partial proteolysis, in immunochemical properties, but not in flavin content.
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PMID:Hepatic microsomal NADPH-cytochrome P-450 reductase from little skate, Raja erinacea. Comparison of thermolability and other molecular properties with a mammalian enzyme. 641 68

The zwitterionic detergent 3-(3-cholamidopropyl)-dimethylammonio-1-propanesulfonate (CHAPS) supports reconstituted cyclohexane hydroxylase activity of cytochrome P-450LM2 and NADPH-cytochrome reductase purified from phenobarbital-induced rabbit liver. Maximum activity (approximately 50% of that with phospholipid) was observed at 2 mM CHAPS. Inhibition took place at higher CHAPS, until at 20 mM CHAPS, no cyclohexane hydroxylase activity was observed. There was little denaturation of the two enzymes under these conditions. At 2 mM CHAPS, P-450LM2 was pentameric (Mr = 250,000) and reductase was dimeric (Mr = 139,500) by sedimentation equilibrium. P-450 was monomeric in 20 mM CHAPS. In addition, a stable complex between the two enzymes was not detected under conditions of maximum activity, even in the presence of saturating substrate. This confirms our previous conclusion that a stable complex between cytochrome P-450LM2 and NADPH-cytochrome P-450 reductase is not a prerequisite for reconstituted xenobiotic hydroxylation (Dean, W. L., and Gray, R. D. (1982) J. Biol. Chem. 257, 14679-14685). Difference spectra of ferric P-450LM2 revealed that below 5 mM CHAPS, the high spin form of the cytochrome was slightly stabilized, while higher CHAPS levels stabilized the low spin form. Monomeric P-450LM2 formed with 20 mM CHAPS catalyzed the hydroxylation of toluene by cumene hydroperoxide. Thus, the reason that monomeric cytochrome P-450LM2 was inactive in NADPH-supported hydroxylation may either be because the bound detergent blocked productive interaction of the cytochrome with reductase or the monomer may be intrinsically incapable of interaction with reductase.
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PMID:Effect of a zwitterionic detergent on the state of aggregation and catalytic activity of cytochrome P-450LM2 and NADPH-cytochrome P-450 reductase. 642 10

The present study was designed to prepare and characterize subcellular fractions from the trunk kidney of the Northern pike (Esox lucius), with special emphasis on the preparation of a microsomal fraction suitable for studying xenobiotic metabolism. The purity of the different fractions obtained by differential centrifugation, as well as the recovery of different organelles, was determined using both enzyme markers and morphological examination with the electron microscope. Finally, the subcellular distributions of several drug-metabolizing enzymes (NADPH-cytochrome c reductase, NADH-ferricyanide reductase, glutathione transferase, epoxide hydrolase) were determined. With the exception of NADPH-cytochrome c reductase, the subcellular distributions obtained here for drug metabolizing and marker enzymes closely resembled those reported for rat liver. NADPH-cytochrome c reductase was apparently partially solubilized here from microsomal vesicles by an endogenous protease, which reduced its usefulness as a marker enzyme and raises questions concerning the measurement of activities catalyzed by the cytochrome P-450 system in these subfractions. In other respects the microsomes and supernatant fraction prepared here from the trunk kidney of the pike seem to be as well suited for investigations of drug metabolism as are the corresponding fractions from rat and pike liver.
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PMID:Preparation and characterization of subcellular fractions suitable for studies of drug metabolism from the trunk kidney of the Northern pike (Esox lucius) and assay of certain enzymes of xenobiotic metabolism in these subfractions. 643 81


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