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

---

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

Treatment of rat liver microsomes with alkaline phosphatase results in a loss in the FMN but not the FAD flavin prosthetic group of NADPH-cytochrome P-450 reductase (Taniguchi, H. and Pyerin, W. (1987) Biochim. Biophys. Acta 912, 295-307). Experiments were carried out to evaluate the effect of preventing electron transfer from the FADH2 to FMN component of the reductase, and subsequent mixed function oxidase activity, on reduction of ferric chelates, production of H2O2, and the generation of .OH-like species by microsomes. Treatment with alkaline phosphatase was confirmed to decrease NADPH-cytochrome c, but not NADPH-ferricyanide, reductase activity by microsomes and by purified NADPH cytochrome P-450 reductase. The oxidation of hydroxyl radical scavenging agents by microsomes and reductase was decreased by the alkaline phosphatase treatment in accordance with the decline in cytochrome c reductase activity. This decrease in hydroxyl radical production occurred in the presence of various ferric chelate catalysts. Rates of microsomal reduction of the ferric chelates were also inhibited after alkaline phosphatase treatment. Production of H2O2 was decreased in accordance to the fall in cytochrome c reductase activity and .OH production. Rates of H2O2 production appeared to be rate-limiting for the overall generation of .OH as the addition of an external H2O2-generating system stimulated .OH production as well as prevented the decline in .OH production caused by the alkaline phosphatase treatment. These results suggest that both the FAD and FMN flavin prosthetic groups of the reductase contribute towards the reduction of various ferric chelates. However, loss of the FMN component and activities dependent on electron transfer from this prosthetic group result in a decrease in H2O2 production, which appears to be responsible for the decline in the generation of .OH-like species by microsomes after treatment with alkaline phosphatase.
...
PMID:Inhibition of the oxidation of hydroxyl radical scavenging agents after alkaline phosphatase treatment of rat liver microsomes. 190 77

The in vivo effect of nicardipine, a well-known calcium antagonist, on microsomal omega-oxidation of laurate in clofibrate-treated rat liver was studied. The 15.3-fold induction of the activity by 2 weeks administration of 0.25% clofibrate in the diet was markedly suppressed to about 6-fold by co-administration of nicardipine at 100 mg/kg body weight. Similarly, the induction of peroxisomal beta-oxidation and carnitine acetyltransferase activities were also suppressed by this simultaneous administration by more than 50%. Although clofibrate also induced the activity of reduced nicotineamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase and increased the hepatic content of cytochrome P-450, no suppressive effect of nicardipine was observed. Contrarily, nicardipine induced the reductase activity and increased the hepatic content of cytochromes P-450 and b5. These results provide the first demonstration of a calcium antagonist, e.g. nicardipine acting as inhibitor of the induction of microsomal omega-oxidation, in association with the inhibition of peroxisome proliferation in animals. The suppression of drug-induced peroxisome proliferation and microsomal omega-oxidation by the calcium antagonist may help in elucidating the causal relationship of the induction mechanisms between peroxisomal and microsomal enzymes.
...
PMID:Co-suppression by nicardipine, a calcium antagonist, of induction of microsomal lauric acid hydroxylation with peroxisome proliferation in clofibrate-treated rat liver. 191 8

We analyzed lipids extracted from human hepatoma HepG2 cells using a high performance liquid chromatograph equipped with a reversed phase column and found a compound with a mass spectrum showing certain diagnostic ion fragments of 1-methoxy-5-polyprenyl-phenol, a known intermediate of ubiquinone biosynthesis. Universally radiolabeled [14C]-p-hydroxybenzoate, a precursor of ubiquinone, was incorporated into the compound on incubation with the cells, suggesting that the compound is a precursor of ubiquinone. The presence of the compound in the microsomal fraction of HepG2 cells was not due to contamination by the mitochondrial fraction because the activity of succinate-cytochrome c reductase in the microsomal fraction was below 1% of that in the mitochondrial fraction, whereas the contents of ubiquinone and the compound in the former were 4.6 and 7.8% of those in the latter, respectively. These results support the hypothesis that ubiquinone biosynthesis might occur in microsomes as well as mitochondria.
...
PMID:An intermediate of ubiquinone biosynthesis exists in the microsomal fraction of HepG2 cells. 196 90

Using the experimental model of partial hepatectomy in the rat, we have examined the relationship between cell division and lipid peroxidation activity. In rats entrained to a regime of 12 h light/12 h dark and with a fixed 8 h feeding period in the dark phase, partial hepatectomy is followed by a rapid regeneration of liver mass with cycles of synchronized cell division at 24 h intervals. The latter phenomenon is indicated in this study by pulses of thymidine kinase activity having maxima at 24 h, 48 h and 72 h after partial hepatectomy. Microsomes prepared from regenerating livers show changes in lipid peroxidation activity (induced by NADPH/ADP/iron or by ascorbate/iron), which is significantly decreased relative to that in microsomes from sham-operated controls, again at 24 h, 48 h and 72 h after the operation. This phenomenon has been investigated with regard to possible underlying changes in the content of microsomal fatty acids, the microsomal enzymes NADPH:cytochrome c reductase and cytochrome P-450, and the physiological microsomal antioxidant alpha-tocopherol. The cycles of decreased lipid peroxidation activity are apparently due, at least in part, to changes in microsomal alpha-tocopherol content that are closely associated in time with thymidine kinase activity.
...
PMID:Studies on the hyperplasia ('regeneration') of the rat liver following partial hepatectomy. Changes in lipid peroxidation and general biochemical aspects. 210 18

Antibodies against cytochrome P-450 are found in some children with autoimmune hepatitis (antiliver/kidney microsome 1) and in patients with ticrynafen hepatitis (antiliver/kidney microsome 2). For an immune reaction against cytochrome P-450 to possibly destroy the hepatocytes, one must assume that cytochrome P-450 is present on the plasma membrane surface of hepatocytes. In a first series of experiments, plasma membranes were prepared with a technique based on the electrostatic attachment of isolated hepatocytes to polyethyleneimine-coated beads. After vortexing, beads were coated with a very pure plasma membrane fraction. Microsomal contamination, judged from the specific activities of glucose-6-phosphatase or NADH-cytochrome c reductase, was less than 1%. Nevertheless, the specific content (per milligram of protein) of CO-binding cytochrome P-450 was 20% of that in microsomes; the specific benzo(a)pyrene hydroxylase activity was 25%, and ethoxycoumarin deethylase 11%. Immunoblots showed the presence of cytochromes P-450 UT-A, UT-H, PB-B, ISF-G and PCN-E, the last three isoenzymes being inducible by, respectively, phenobarbital, 3-methylcholanthrene and dexamethasone. In a second series of experiments, nonpermeabilized isolated hepatocytes from untreated rats were incubated with anticytochrome P-450 antibodies. Immunofluorescence and immunoperoxidase staining confirmed the presence of cytochromes P-450 UT-A, PB-B and ISF-G on the membrane. In a last series of experiments, human antiliver-kidney microsomal 1 antibodies were found to react specifically with rat liver plasma membrane cytochrome P-450 UT-H (IID subfamily). We conclude that several cytochrome P-450 isoenzymes are present, active and inducible on the plasma membrane surface of hepatocytes. It is therefore conceivable that immunization against plasma membrane cytochrome P-450 might lead to the immunological destruction of hepatocytes in some patients.
...
PMID:Presence of functional cytochrome P-450 on isolated rat hepatocyte plasma membrane. 211 12

The chemical and enzymatic pathways of vitamin K1 epoxide and quinone reduction have been investigated. The reduction of the epoxide by thiols is known to involve a thiol-adduct and a hydroxy vitamin K enolate intermediate which eliminates water to yield the quinone. Sodium borohydride treatment resulted in carbonyl reduction generating relatively stable compounds that did not proceed to quinone in the presence of base. NAD(P)H:quinone oxidoreductase (DT-diaphorase, E.C. 1.6.99.2) reduction of vitamin K to the hydroquinone was a significant process in intact microsomes, but 1/5th the rate of the dithiothreitol (DTT)-dependent reduction. No evidence was found for DT-diaphorase catalyzed reduction of vitamin K1 epoxide, nor was it capable of mediating transfer of electrons from NADH to the microsomal epoxide reducing enzyme. Purified diaphorase reduced detergent- solubilized vitamin K1 10(-5) as rapidly as it reduced dichlorophenylindophenol (DCPIP). Reduction of 10 microM vitamin K1 by 200 microM NADH was not inhibited by 10 microM dicoumarol, whereas DCPIP reduction was fully inhibited. In contrast to vitamin K3 (menadione), vitamin K1 (phylloquinone) did not stimulate microsomal NADPH consumption in the presence or absence of dicoumarol. DTT-dependent vitamin K epoxide reduction and vitamin K reduction were shown to be mutually inhibitory reactions, suggesting that both occur at the same enzymatic site. On this basis, a mechanism for reduction of the quinone by thiols is proposed. Both the DTT-dependent reduction of vitamin K1 epoxide and quinone, and the reduction of DCPIP by purified DT-diaphorase were inhibited by dicoumarol, warfarin, lapachol, and sulphaquinoxaline.
...
PMID:Vitamin K1 2,3-epoxide and quinone reduction: mechanism and inhibition. 211 31

Induction of hepatic monooxygenases reflected by 7-ethoxycoumarin O-deethylase has been proposed to be associated with the initiation of liver damage. This study investigated a possible correlation between 7-ethoxycoumarin O-deethylase, reduced nicotinamide adenine dinucleotide phosphate cytochrome c reductase and benzypyrene hydroxylase activity in liver biopsy specimens of 31 patients with liver disease and antipyrine elimination, an in vivo parameter of hepatic monooxygenase activity. No correlation was found between the enzyme activities and antipyrine clearance or half-life. When microsomal enzyme activities were compared with the formation rate of 4-hydroxyantipyrine, 3-methylhydroxyantipyrine, and norantipyrine, a correlation was found only between benzo[alpha]pyrene hydroxylase and 3-methylhydroxyantipyrine (r = 0.89; p less than 0.0005). There was also a correlation between 7-ethoxycoumarin O-deethylase and reduced nicotinamide adenine dinucleotide phosphate cytochrome c reductase (0.56; p less than 0.05). Our data suggest that antipyrine elimination is not related to 7-ethoxycoumarin O-deethylase activity in liver disease. However, the formation rate of antipyrine metabolites, rather than antipyrine half-life and clearance, may correlate with the activity of certain microsomal enzymes.
...
PMID:Antipyrine elimination and hepatic microsomal enzyme activity in patients with liver disease. 211 50

Hepatic and renal microsomal electron transport components and erythrocyte delta-aminolevulinate dehydratase were investigated in adult male rats exposed to 0, 50, 200 and 600 ppm tetrachloroethylene for 4 weeks. Body weight and liver weight showed a significant decrease only in the 600 ppm group. A dose-dependent decrease in erythrocyte delta-aminolevulinate dehydratase was observed at 200 and 600 ppm. Serum transaminase activity (SGPT) showed an increase in the 600 ppm group only. Hepatic and renal microsomal protein content showed an increase in all groups except in the kidneys of the 600 ppm group. Induction of hepatic cytochrome b5 activity was observed in all groups. However, hepatic cytochrome P-450 showed an induction and slight inhibition at 200 and 600 ppm respectively, without any alteration at 50 ppm. Renal microsomal cytochrome P-450 activity was induced in all groups. Induction of hepatic and renal NADPH cytochrome c reductase activity was observed at 600 ppm, but no alteration was seen at 50 and 200 ppm. These results indicate that chronic inhalation of tetrachloroethylene at higher levels alters mixed-function oxidase and heme metabolism.
...
PMID:Chronic inhalation effects of tetrachloroethylene on hepatic and renal microsomal electron transport components and delta-aminolevulinic acid dehydratase in rats. 212 80

Previous studies have shown that vertebrate rod outer segments (ROS) have a light activated phospholipase C which hydrolyzes phosphatidylinositol-4,5-bisphosphonate (PIP2). Three different experimental approaches have been used to test the hypothesis that the phosphatidylinositol (PI) biosynthetic cycle is present in ROS and that PIP2 can be regenerated from DG independent of rod inner segments. In the first study, enzyme activities of the PI cycle were assayed simultaneously in the presence of CTP, myo-inositol and [gamma-32P]ATP using endogenous lipids as substrates. Under these conditions, broken (leaky) ROS prepared by continuous sucrose gradient centrifugation showed PI, PIP and DG kinase activities similar to those found in intact ROS and non-ROS membranes, whereas PI synthetase activity was much lower in the leaky ROS than in the other two fractions. The relative distribution of PI synthetase specific activity in the three membrane preparations was similar to that of the microsomal enzyme marker cytochrome c reductase. ROS prepared by discontinuous sucrose gradient centrifugation showed only 2-3% of whole homogenate PI synthetase or phosphatidyl: cytidyl transferase activities, and the distribution of activities was the same as for microsomal and mitochondrial marker enzymes. In the second study, whole retinas were incubated with myo-[2-3H]inositol or [2-3H]glycerol in vitro, and the time course of incorporation of radioactivity into PI and other phospholipids was determined for ROS and three other retinal fractions. Over a 10-hr period, the rate of incorporation of myo-[2-3H]inositol or [2-3H]glycerol into PI in ROS was lowest among the various retinal fractions. In the third study, chemical analysis of the molecular species composition of PI, DG and phosphatidic acid (PA) from ROS shows that PA is substantially different from PI and DG, the latter two being quite similar. These results are consistent with a precursor-product relationship between PI and DG, but not with the conversion of DG to PA or of PA to PI. Taken together, these three studies indicate that ROS do not have PI synthetase or phosphatidyl: cytidyl transferase activities, but do have DG, PI and PIP kinase activities. Thus, the PI in ROS lost through rapid turnover must be replaced with molecules derived from de novo synthesis in the inner segment of the photoreceptor cell.
...
PMID:Phosphoinositide metabolism in frog rod outer segments. 216 31

Hepatic ischemia induced in vivo by ligation of the left hepatic lobe of rats for up to 2 hr had no effect on cytochrome P-450, cytochrome c reductase, or lobe histology; however, cytochrome b5 increased with ischemia duration. Ethylmorphine demethylation decreased 35% after 2 hr of ischemia. Reperfusion of tissue previously made ischemic for up to 2 hr was associated with appreciable necrosis as well as decreases in cytochrome P-450, cytochrome b5, cytochrome c reductase, and ethylmorphine demethylation. Serum alanine transaminase and aspartate transaminase concentrations were increased by reperfusion of previously ischemic tissue. Reperfusion of the previously ischemic lobe for 18 hr was associated with a greater loss of cytochromes P-450 and b5, cytochrome c reductase, and ethylmorphine demethylation than reperfusion for 1 hr. The total decrease in cytochrome P-450 and b5 content was equal to the decrease in total microsomal heme content, although cytochrome P-450 decreased more than cytochrome b5. Ethoxyresorufin deethylation by hepatic microsomes from 3-methylcholanthrene-treated rats was decreased by ischemia-reperfusion; however, pentoxyresorufin dealkylation by hepatic microsomes from phenobarbital-treated rats was not, suggesting specific cytochrome P-450 isozyme loss. In vitro NADPH-dependent lipid peroxidation in hepatic microsomes from control and phenobarbital- and 3-methylcholanthrene-treated rats resulted in a selective decrease of ethoxyresorufin but not pentoxyresorufin dealkylation, similar to that observed in livers subjected to ischemia-reperfusion in vivo. These data suggest that cytochrome P-450, ethylmorphine demethylation, and ethoxyresorufin deethylation are more susceptible to ischemia-reperfusion injury than cytochrome b5 or pentoxyresorufin dealkylation.
...
PMID:Effects of hepatic ischemia-reperfusion injury on the hepatic mixed function oxidase system in rats. 225 Jun 63


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

---