Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.6.99.3 (diaphorase)
5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methyl sterol oxidase of microsomal synthesis of cholesterol from lanosterol is a mixed-function oxidase that is dependent upon reduced pyridine nucleotide. The methyl sterol oxidase, as well as NADH-cytochrome c reductase, in intact rat liver microsomes are inhibited by anti-cytochrome b5 immunoglobulin, but NADPH-cytochrome c reductase is not affected. There is a decreased time lag prior to onset of reoxidation of steady state levels of reduced cytochrome b5 when 4-methyl sterol oxidase substrates are present. Trypsin treatment of microsomes destroys cytochrome b5 with loss of methyl sterol oxidase activity. Activity is restored by addition of purified cytochrome b5 to trypsin-treated microsomes. Initial attempts to solubilize and purify 4-methyl sterol oxidase have been only partially successful due to the extreme lability of the oxidase. However, DEAE-cellulose column chromatography of a detergent extract of microsomes yields a fraction that contains the oxidase, lipids, and NADH-cytochrome b5 reductase but is free of cytochrome b5. Oxidation of 4 alpha [30-3H] methyl-5 alpha-cholest-7-en-3 beta-ol by methyl sterol oxidase in this isolated fraction can be fully restored by the addition of purified liver microsomal cytochrome b5. These results strongly support the suggestion that membrane-bound cytochrome b5 of rat liver microsomes is an obligatory electron carrier from NADH to 4-methyl sterol oxidase.
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PMID:Total enzymic synthesis of cholesterol from lanosterol. Cytochrome b5-dependence of 4-methyl sterol oxidase. 722 57

The rotenone-insensitive NADH-cytochrome c reductase activity and cytochrome b5 content in mitochondria and microsomes of liver of 1-, 3-, 12- and 24-month-old rats were studied. Thyroxine injection caused a considerable decrease in the microsomal activity in all age groups under study; in mitochondria this effect was increased with age. The decrease of the cytochrome b5 content was maximal in the microsomes and mitochondria of 12- and 24-month-old animals and was insignificant in 1-month-old rats. It was assumed that the age variations in regulation of the outer mitochondrial membrane function can be due changes in their population.
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PMID:[Effect of thyroxine on the NADH cytochrome c reductase activity of microsomes and outer mitochondrial membrane of rat liver depending on age]. 730 1

The participation of OM cytochrome b in the rotenone-insensitive NADH-cytochrome c reductase activity of rat tissues was investigated in comparison with that of cytochrome b5, by using antibodies against these two cytochromes. The specificity of each antibody was confirmed by inhibition studies of NADH-cytochrome c reductase activities reconstituted from purified cytochromes and NADH-cytochrome b5 reductase. OM cytochrome b-mediated NADH-cytochrome c reductase activity was found in various tissues including liver, kidney, heart, and brain. The contribution of this activity to the total rotenone-insensitive NADH-cytochrome c reductase activity was high in heart and brain cells. NADH-cytochrome c reductase activity mediated by OM cytochrome b was principally localized in mitochondrial outer membrane. Immunoadsorption studies using antibody-coated polyacrylamide beads showed that significant OM cytochrome b-mediated activity is present in the microsomal membrane, and that cytochrome b5-mediated activity also exists in the mitochondrial outer membrane.
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PMID:Cytochrome b5-like hemoprotein of outer mitochondrial membrane: OM cytochrome b. II. Contribution of OM cytochrome b to rotenone-insensitive NADH-cytochrome c reductase activity. 735 42

The subcellular distribution of NADH-cytochrome b5 reductase in rat liver cells was reinvestigated. In fresh heavy and light Golgi fractions (GF3 and GF1 + 2) and in mitochondria, the specific activity of rotenone-insensitive NADH-cytochrome c reductase was approximately 100, 60, and 30%, respectively, of the value found in microsomes. However, the Golgi enzyme was unstable inasmuch as pelleting and resuspending the fresh fractions resulted in a considerable inactivation (40--60%), which was further increased with subsequent storage at 4 degrees C. A similar inactivation was observed using cytochrome b5 but not ferricyanide as electron acceptor. The inactivation of Golgi NADH-cytochrome c reductase activity was independent of the protein concentration of the fractions during storage, was unaffected by the addition of the antioxidant butylated hydroxytoluene, but was partly prevented by buffering the fractions at neutral pH and by storage at--20 degrees C. A total Golgi fraction was analyzed by density equilibration on continuous sucrose gradients after exposure to digitonin. As expected, the distribution of both protein and galactosyl transferase were shifted to higher densities by this treatment. However, not all galactosyl transferase-bearing elements were shifted to the same extent by exposure to the detergent, suggesting a biochemical heterogeneity of the Golgi complex. In contrast to their behavior in microsomes, the distribution of NADH-cytochrome c reductase and cytochrome b5 of Golgi fractions was shifted by digitonin, although to a lesser extent than that of galactosyl transferase. These results indicate that NADH-cytochrome b5 reductase is an authentic component of Golgi membranes, as well as of microsomes and of mitochondria. The conflicting results reported in the past on the Golgi localization of the enzyme could be due, on the one hand, to the differential lability of the activity in its various subcellular locations and, on the other, to the heterogeneity of the Golgi complex in terms of both cholesterol and enzyme distribution.
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PMID:Localization and biosynthesis of NADH-cytochrome b5 reductase, an integral membrane protein, in rat liver cells. I. Distribution of the enzyme activity in microsomes, mitochondria, and golgi complex. 739 Nov 31

NADH-cytochrome b5 reductases of rat liver microsomes, mitochondria, and heavy and light Golgi fractions (GF3 and GF 1+2) were compared by antibody inhibition and competition experiments, by peptide mapping, and by CNBr fragment analysis. The water-soluble portion of the microsomal enzyme, released by lysosomal digestion and purified by a published procedure, was used to raise antibodies in rabbits. Contaminant antimicrosome antibodies were removed from immune sera by immunoadsorption onto the purified antigen, and the F(ab')2 fragments of the pure antireductase antibody thus obtained were found to inhibit the NADH-cytochrome c reductase activity equally well in the four membrane fractions investigated, with similar dose-response relationships. Moreover, the purified water-soluble fragment of microsomal reductase, which by itself is very inefficient in reducing cytochrome c, competed for antibody binding with the membrane-bound enzymes, and therefore prevented the inhibition of their activity not only in microsomes but also in the other fractions. The reductases isolated from detergent-solubilized microsomes, mitochondria, GF3, and GF1+2 by immunoadsorption had identical mobilities in SDS polyacrylamide gels. The corresponding bands were eluted from gels, fragmented with pepsin or CNBr treatment, and the two families of peptides thus obtained were analyzed by two-dimensional mapping and SDS polyacrylamide gel electrophoresis, respectively. Both analyses failed to reveal differences among reductases of the four fractions. These findings support the hypothesis that NADH-cytochrome b5 reductase in its various subcellular locations is molecularly identical.
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PMID:Localization and biosynthesis of NADH-cytochrome b5 reductase, an integral membrane protein, in rat liver cells. II. Evidence that a single enzyme accounts for the activity in its various subcellular locations. 739 Nov 32

The presence of cytochromes b5, P-450 and P-420 and activities of NADH- and NADPH-cytochrome c redutases were determined in plasma membranes isolated from microvilli of the chick and rat intestinal epithelium and erythrocyte membranes from chick, rat and man. The results are compared with the amounts of these components found in microsomal fractions from intestinal epithelium and in nuclear membranes from chick erythrocytes. Plasma membranes from intestinal microvilli and from erythrocytes contained significant amounts of NADH-cytochrome c reductase activity and of a pigment spectrophotometrically indistinguishable from rat liver microsomal cytochrome b5. In addition, cytochrome b5 fragments were prepared from the membranes by limited trypsin digestion and consisted of two to four components with Mr values in the range 10 000-13 500. In low-temperature difference spectra, the presence of a second cytochrome was noted which was similar to cytochrome P-420. Cytochrome P-450 and NADPH-cytochrome c reductase activities were not detected in plasma membrane fractions in significant concentrations but were present in the corresponding endomembrane fractions. These findings in highly purified, well defined plasma membrane fractions, in which contamination by endomembranes is minimal, strengthen the evidence for the existence of cytochrome-containing redox systems in plasma membranes of various cells and suggest that such redox components are general components of the cell surface. Possible functions and origins of these redox components in plasma membranes are discussed.
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PMID:Plasma membranes from intestinal microvilli and erythrocytes contain cytochromes b5 and P-420. 740 43

Hypothyroid rats were prepared by thyroidectomy and maintenance on a low-iodine diet (group A); Group B was additionally pretreated with 0.5 mCi of 131I as NaI, given intraperitoneally. Liver microsomes obtained from hypothyroid and normal rats were compared. After fasting and refeeding on 20% sucrose solution, high levels of microsomal fatty-acyl-CoA delta 9-desaturase (as measured spectrophotometrically by the rate constants for cytochrome b5 reoxidation) were induced in all the normal animals, half of the group A hypothyroid rats, and none of the group B hypothyroid rats. Hypothyroidism did not change desaturase Arrhenius profiles or V and Km for NADH-cytochrome c reductase, but increased content of cytochrome b5. The inability of adequately hypothyroid rats to induce the delta 9-desaturase seems to be specific, in that injection of methylcholanthrene successfully induced microsomal benzpyrene monooxygenase activity and increased cytochrome b5 contents in hypothyroid animals. The defects in overall fatty acyl desaturation reported in hypothyroid animals [Landriscina, C., Gnoni, G. V. & Quagliariello, E. (1976) Eur. J. Biochem. 71, 135-143] are suggested to be due to deficiencies in the specific desaturase(s).
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PMID:Thyroid control over biomembranes. Liver-microsomal cytochrome b5 in hypothyroidism. 740 82

Human cytochrome CYP3A4 is the most abundant of all the P450s in human liver and is involved in the metabolism of many environmental toxicants and drugs. Kinetic studies with CYP3A4 have been hampered due to low activity of this enzyme obtained from recombinant gene expression systems or difficulty in reconstituting activity with the native enzyme purified from human liver. To overcome these obstacles, we have expressed high levels of catalytically active CYP3A4 and human NADPH-cytochrome P450 reductase (CYPOR) together in two insect cell lines, Spodoptera frugiperda (Sf9) and Trichoplusia ni (T.ni), via a single recombinant baculovirus carrying both cDNAs (CYP3A4-OR). Microsomes containing recombinant CYP3A4-OR from these cell lines were up to 50-times more active in testosterone 6 beta-hydroxylase activity than recombinant CYP3A4 expressed alone and supplemented with purified rabbit CYPOR. The spectral P450 content of CYP3A4-OR T.ni microsomes was 107 pmol/mg microsomal protein and the cytochrome c reductase activity was 3904 units/mg. Recombinant CYP3A4-OR was catalytically similar to human liver CYP3A4 based on similarities in the testosterone metabolite profile, time course of metabolite formation, Vmax and Km values (for CYP3A4-OR, Vmax was 8.8 nmol/min/mg microsomal protein [70 nmol/min/nmol CYP3A4] and Km was 33 microM), the extent of inhibition by 100 microM troleandomycin (> 75%) in the presence of 25 microM testosterone, and the degree of P450 activation in the presence of 20 microM 7,8-benzoflavone. The coexpression of recombinant cytochrome b5 with CYP3A4-OR did not result in an additional increase in CYP3A4-OR activity.
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PMID:CYP3A4 expressed by insect cells infected with a recombinant baculovirus containing both CYP3A4 and human NADPH-cytochrome P450 reductase is catalytically similar to human liver microsomal CYP3A4. 777 80

The effect of single or daily oral administration of hot water extracts (HWE) from Byakushi or Ogon on rat hepatic drug-metabolizing enzymes were investigated in vivo. Enzymes were measured for 3 to 72 hr after single oral administration of HWE at the dose of 1.0 g/kg or 5.0 g/kg. Administration of 1.0 g/kg of Byakushi and 5.0 g/kg of Ogon inhibited aniline hydroxylase activity, while 5.0 g/kg of Byakushi inhibited it in the early phase, but increased it in the late phase. Byakushi inhibited aminopyrine N-demethylase activity, while 5.0 g/kg of Ogon increased it. Byakushi and Ogon decreased the amount of cytochrome P-450. Byakushi and Ogon increased the amount of cytochrome b5. Byakushi increased cytochrome c reductase activity 3 hr after administration and decreased it 6 and 12 hr after administration. In contrast, 1.0 g/kg of Ogon decreased cytochrome c reductase activity, and 5.0 g/kg increased it 6 hr after administration and decreased it 12 hr after administration. At 24 hr after the last administration to animals treated with a regimen of once a day administration of the HWE (0.1 or 1.0 g/kg) of Byakushi or Ogon for 14 days, the enzymes were measured. Byakushi decreased aminopyrine N-demethylase activity, the amount of cytochrome P-450, and cytochrome c reductase activity. Ogon decreased cytochrome c reductase activity. Byakushi altered the composition of cytochrome P-450 isozyme after daily administration.
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PMID:[Effects of byakushi and ogon on the hepatic drug metabolizing enzymes in rats]. 782 26

The effects of doxapram on the hepatic microsomal mono-oxygenase system of male and female rats were investigated. Male and female rats were administered doxapram (10-120 mg kg-1 day-1, i.p.) for 4 days. In female rats, administration of doxapram (20, 40, 60, 80, 100 and 120 mg kg-1) elevated the parameters in a dose-dependent manner while doxapram (100 and 120 mg kg-1) elevated the levels of cytochrome P450 and hexobarbitone hydroxylase in male rats. Doxapram (40 mg kg-1) caused induction of hepatic drug metabolism typified by an increase of hepatic microsomal cytochrome P450 content and activities of hexobarbitone hydroxylase, benzphetamine N-demethylase and ethylmorphine N-demethylase in female rats, but no change in male rats. These findings were supported by the results of SDS/polyacrylamide-gel electrophoresis. However, 7-ethoxycoumarin O-de-ethylase and arylhydrocarbon hydroxylase activities were significantly increased in male rats. NADPH-cytochrome c reductase and NADH-cytochrome c reductase activities, and cytochrome b5 content were unaffected in rats of both sexes. The sex-dependent cytochrome P450 species may be selectively sensitive to the action of doxapram.
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PMID:Sex-related differences in rat liver microsomal enzymes and their induction by doxapram. 790 40


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