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 endogenous formation of apparent total N-nitroso compounds (ATNC) has been investigated in germ-free (GF) and conventional (CV) microflora rats as a function of the drinking-water nitrate concentration. ATNC levels were below the 40 micrograms (N-NO)/kg detection limit in the blood, liver, kidney, spleen and small intestine of all CV and GF rats. For the CV rats ATNC were detected in concentrations of up to 370 micrograms (N-NO)/kg in the large intestine and up to 50 micrograms (N-NO)/kg in the stomach and there was a significant positive correlation between ATNC formation and the drinking-water nitrate level. Comparison of these results with those from GF rats showed that the ATNC in the stomach and large intestine of the CV animals were formed by microbial action, most probably involving bacterial nitrate-reductase activity.
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PMID:An investigation of the endogenous formation of apparent total N-nitroso compounds in conventional microflora and germ-free rats. 318 35

The B1 subunit of ribonucleotide reductase formed two-dimensional crystals when bound to and effector nucleotide linked to lipids in planar layers at the air/water interface. The effector lipid consisted of dATP coupled through the gamma-phosphoryl group and an epsilon-aminocaproyl linker to phosphatidylethanolamine. Two-dimensional crystals of B1 reductase, like those of antibodies and cholera toxin obtained previously, formed under physiologic conditions of pH and ionic strength, with no precipitant added to the solution. There was, however, a requirement for dTTP in the solution, presumably to ensure binding of the dATP-lipid at only one of two effector sites on the enzyme. Diffraction from the crystals extended to 18-A resolution in negative stain, with unit cell parameters a = 110 A, b = 277 A, and gamma = 90 degrees. Image analysis revealed the B1 dimer as a pair of roughly cylindrical objects, each 105-109 A in length and 31-34 A in diameter.
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PMID:Two-dimensional crystals of enzyme-effector complexes: ribonucleotide reductase at 18-A resolution. 332 9

The hydrogen transfer from NADPH was studied in the elongation of arachidoyl-CoA (20:0-CoA) and arachidonoyl-CoA (20:4-CoA) in swine cerebral microsomes. Previously, we showed that four deuterium atoms (2H) were transferred stereospecifically from (4S)-[4-2H1]NADPH in the elongation of 20:0-CoA to 24:0 (Yoshida, S., Takeshita, M. and Kawaguchi, A. (1984) Biochem. Biophys. Res. Commun. 124, 322-328), and that three deuterium atoms were transferred from 2H2O in the elongation of 20:4-CoA to 22:4. The deuteride transfer from (4S)-[4-2H1]NADPH was observed in the elongation of 20:4-CoA to 24:4, by the technique of mass fragmentography using the chemical ionization method, and, in this case, two 2H were transferred to 24:4. No deuteride was transferred from (4R)-[4-2H1]NADPH in the elongation of 20:0-CoA and 20:4-CoA. Moreover, the condensation product (3-keto-fatty-acyl-CoA) which was formed in the elongation without NADPH could be reduced by the addition of NADPH and sodium hydrosulfite, for the elongation of 16:0-CoA and 20:4-CoA, while the condensation product from 20:0-CoA could be reduced only by NADPH, but not by hydrosulfite. The hydrosulfite did not produce the final elongation products from 20:0-CoA, 16:0-CoA or 20:4-CoA. These results suggested that the hydride was transferred from NADPH stereospecifically only in the elongation of 20:0-CoA in the step of 3-ketoacyl-CoA reduction by the reductase which might be different from that for the elongation of 16:0-CoA and 20:4-CoA in which the proton exchange might occur via a water proton in the reduction of 3-ketoacyl-CoA. Accordingly, the hydride transfer might occur from NADPH in the step of 2,3-enoyl reduction in the elongation of 20:0-, 16:0- and 20:4-CoA.
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PMID:Hydrogen transfer by NADPH-dependent reductases in elongation of very-long-chain saturated and polyunsaturated fatty-acyl-CoA in swine cerebral microsomes. 334 46

1. The b-type haem centres of the three (alpha, beta and gamma) subunit nitrate reductase from Paracoccus denitrificans have been analysed by redox potentiometry. Two components were identified with mid-point potentials +95 mV and +210 mV. 2. Washing, in the absence of Mg2+ ions, of cytoplasmic membrane vesicles from P. denitrificans promoted selective release of nitrate reductase activity. The released enzyme was purified by chromatography and shown to contain alpha and beta, but not gamma polypeptides. A haem spectrum was absent, consistent with the lack of the gamma subunit. The alpha and beta polypeptides of the water-soluble nitrate reductase had molecular masses that were identical to those of the detergent-purified enzyme and also of the nitrate reductase in cytoplasmic membranes. This observation, together with the failure of protease inhibitors to prevent release from the membrane, indicates that the release is not related to limited proteolysis of the alpha and/or beta polypeptides. The relative molecular mass of the water-soluble alpha beta enzyme was estimated to be approximately 200,000. 3. The water-soluble nitrate reductase was released from intact inverted cytoplasmic membrane vesicles as judged by loss of NADH-NO3- reductase activity and retention by the vesicles after washing of uncoupler-sensitive NADH-oxidase activity. These observations show that alpha and beta polypeptides, and therefore the active site for nitrate reduction, are located on the cytoplasmic side of the membrane. 4. Attempts to reverse the nitrate reductase activity of the enzyme, using nitrate as reductant plus ferricyanide or chlorate as tested oxidants, were unsuccessful. The implications for the mechanism of the enzyme are discussed.
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PMID:Respiratory nitrate reductase from Paracoccus denitrificans. Evidence for two b-type haems in the gamma subunit and properties of a water-soluble active enzyme containing alpha and beta subunits. 337 62

We describe the metabolism of cortisol (F) in three children, two of them siblings, with apparent mineralocorticoid excess (AME). As with prior patients with AME, oxidation of F to cortisone (E) was impaired, but reduction of E to F was not. We propose that this metabolic defect is caused by deficient 11-dehydrogenase associated with unimpaired 11-reductase. The following supporting observations were made: urinary C21 11-hydroxy metabolites exceeded C21 11-oxo metabolites: ratio of urinary cortols to cortolones, 6.6 +/- 2.8 (+/- SD; normal, 0.47); tetrahydrocortisol (THF) and alloTHF to tetrahydrocortisone, 14.6 +/- 5.6 (normal, approximately 1); normal subjects oxidized [11 alpha-3H]F with transfer of 3H to water; the patients did not; 11-hydroxy, but not 11-oxo, C19 steroids were excreted into the urine; and fibroblasts from patients had 5 times more 11-reductase activity than normal subjects, though fibroblasts from neither group had 11-dehydrogenase activity. Other defects of cortisol metabolism not directly associated with 11-dehydrogenase deficiency were found: impaired conversion of tetrahydro to hexahydro neutral steroids, indicating defective reductive metabolism of the side chain; depressed F production rate and increased half-life of circulating F, resulting in normal blood levels of F; increased excretion of unconjugated F metabolites; and decreased excretion of THF relative to alloTHF, consistent with a 5 beta-reductase defect. Excretion of acidic metabolites of F (cortoic acids) was within the normal range. However, little or no 20 beta-hydroxy acids were excreted, while the level of urinary 20 alpha-hydroxy acids was increased. The 11-hydroxy to 11-oxo ratio of acid metabolites was similar to values in normal subjects. The proportion of cortoic acids relative to neutral hexahydro metabolites was increased (0.37 to 1.27 in patients; 22 in normal subjects). We conclude that children with AME have multiple defects in the conversion of F to neutral metabolites, while metabolism to cortoic acids was less extensively affected. How the defects in cortisol metabolism and the symptoms of AME are related remains to be determined.
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PMID:The syndrome of apparent mineralocorticoid excess: its association with 11 beta-dehydrogenase and 5 beta-reductase deficiency and some consequences for corticosteroid metabolism. 346 Sep 96

Ketoconazole (K) is an antifungal imidazole derivative which is a potent inhibitor of steroid biosynthesis in rodents and humans. To study the effect of K on rat ovarian steroidogenesis we measured the activities of five ovarian microsomal steroidogenic enzymes in K-treated rats and controls. Thirty hypophysectomized, gonadotropin-treated female adult rats were given either 2 mg K or water every 12 hours by mouth during 5 days. Mean ovarian weight was similar in both groups of animals. The K-treated group had an estradiol (E) serum concentration of 176 +/- 48 pg/ml whereas it was 278 +/- 56 pg/ml in the control group (NS). The K-treated animals had decreased activities of the 17,20-desmolase, 17-ketosteroid-reductase and aromatase enzymes. The 3 beta hydroxysteroid-dehydrogenase and 17-hydroxylase activities were similar in both groups. We conclude that K directly inhibits the activities of the 17,20-desmolase, 17-ketosteroid-reductase and aromatase enzymes in the rat ovary.
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PMID:Effects of ketoconazole on rat ovarian steroidogenic enzymatic activities. 348 74

Ovarian slices of the European eel at the silver stage were incubated with 4 tritiated precursors (pregnenolone, progesterone, androstenedione, testosterone) in the presence or not of an inhibitor of 11 beta-hydroxylase activity, metopirone. Ether extracts were submitted to a gradient elution chromatography on celite columns. Isolated peaks were identified by isopolarity on TLC, microchemical reactions and recrystallization to constant specific activity. Interpretation of the results shows that the ovary of the European eel contains the following enzymes: a 3 beta-hydroxysteroid dehydrogenase, 5----4-ene-isomerase complex, a 17 alpha-hydroxylase, a C21-C19 desmolase, a 17 beta-hydroxysteroid oxidoreductase, a 5 alpha-reductase, a 3 beta-hydroxysteroid oxidoreductase and an aromatase complex. Metopirone effect indicates the presence of an 11 beta-hydroxylase activity. At this stage, 5 beta-reductase, 20 beta-reductase and 21-hydroxylase activities are not detected in the ovary. Water-soluble steroids were formed from all the precursors used. It appears that the ovarian biosynthesis is orientated towards the production of 5 alpha-reduced compounds and that this might limit the production of 17 beta-estradiol by lowering the amount of disposable endogenous precursors.
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PMID:Ovarian metabolic pathways of steroid biosynthesis in the European eel (Anguilla anguilla L.) at the silver stage. 351 3

Ferredoxin which had been modified with glycine ethylester in the presence of a water-soluble carbodiimide to the extent of one carboxyl-group modified per ferredoxin was subjected to peptide mapping in an attempt to locate the site(s) of modification. The peptide mapping was done by HPLC and analysis of the resulting chromatogram allowed assignment of peaks to various segments in the amino acid sequences of the two isozymes of ferredoxin. The modified ferredoxin appeared to be a mixture of ferredoxin derivatives in which modification had occurred in three areas of the molecule. Although unable to identify the specific residues modified, it has been shown that modification is localized in the regions of residues 26-30, 65-70, and 92-94. The possibility that these regions of ferredoxin may define its binding site for ferredoxin: NADP reductase is discussed. Peptide mapping studies on a covalently linked adduct between ferredoxin and ferredoxin: NADP reductase also support these regions of ferredoxin as being important in the interaction between the two proteins.
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PMID:Chemical modification and cross-linking as probes of regions on ferredoxin involved in its interaction with ferredoxin: NADP reductase. 352 79

The expression of four cytochrome (cyt.) P-450 isoenzymes has been studied in preneoplastic and neoplastic lesions during the course of nitrosamine-induced hepatocarcinogenesis in the female Wistar rat. Following exposure to diethylnitrosamine (50 or 100 ppm in the drinking water) for 10 days, animals were taken sequentially, and the livers were analyzed for the evolution of adenosine triphosphatase deficient focal lesions. These lesions were subdivided into different phenotypes with regard to their cyt. P-450 isoenzyme expression using serial frozen sections. Our results demonstrate that about 40% of the adenosine triphosphatase-deficient lesions show concomitant alterations in their cyt. P-450 isoenzyme contents. Of these lesions, islets which are characterized by decreased levels of at least three cyt. P-450 isoenzymes show a dramatic increase in their volumetric fraction of liver tissue with progression of time. Although only very few lesions express this phenotype, the contribution to the volumetric fraction of islet tissue raises from about 2% at 10 weeks to about 60% at 35 weeks after cessation of diethylnitrosamine treatment. By contrast, lesions which express less than two alterations in cyt. P-450 isoenzyme levels develop relatively slowly. Similar results were obtained when animals were exposed continuously to diethylnitrosamine for a period of up to 8 weeks. Following treatment of islet-bearing animals with phenobarbital, an induction of cyt. P-450 isoenzymes and NADPH-cyt. P-450-reductase was observed within preneoplastic and neoplastic lesions. This induction was most pronounced in large, expansively growing nodules, a type of lesion which displayed decreased levels of these enzymes in livers of animals not treated with phenobarbital. The elevation of the cyt. P-450 isoenzymes disappeared within 2 to 3 weeks after cessation of inducer treatment. Our results indicate that a high proportion of rapidly growing lesions has assumed a constitutive deficiency in cyt. P-450 isoenzyme expression during nitrosamine-induced hepatocarcinogenesis. This deficiency, however, is not an irreversible quality, since individual cyt. P-450 isoenzymes can be markedly induced by treatment with an enzyme inducer like phenobarbital. Thus, the observed decrease in cyt. P-450 expression during development of malignancy does not result from alterations in the cyt. P-450 encoding structural genes but may rather be related to abnormalities in the function of regulatory systems of a higher order which may play a central role in the maintenance of cell homeostasis.
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PMID:Development of cytochrome P-450-altered preneoplastic and neoplastic lesions during nitrosamine-induced hepatocarcinogenesis in the rat. 356 9

Mitochondrial NADH dehydrogenase has been purified from rat liver mitochondria by protamine sulfate fractionation and DEAE-Sephadex chromatography. The enzyme is water-soluble and its molecular weight has been estimated at 400 +/- 50 kilodaltons. NADH-ferricyanide reductase and NADH cytochrome c reductase activities have been studied and the kinetic parameters have been determined. Both substrates, NADH and the electron acceptor (ferricyanide or cytochrome c) have an inhibitor effect on the reductase activities and the kinetic mechanism of the enzyme is ping-pong bi-bi.
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PMID:Isolation and characterization of a NADH-dehydrogenase from rat liver mitochondria. 361 8


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