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1.
The metabolism and binding of catecholamines by the hepatic microsomal mixed-function oxidase of the rat.
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Noradrenaline and adrenaline were metabolized by an NADPH- and oxygen-dependent process located within the hepatic microsomal fraction of the rat. Metabolism was inhibited by CO and compound SKF 525A, but not by pargyline, an inhibitor of monoamine oxidase, or by 3,4-dimethoxy-5-hydroxybenzoic acid, an inhibitor of catechol O-methyltransferase. It is concluded that the enzyme system responsible for the metabolism of the catecholamines was the microsomal mixed-function oxidase. The Km for noradrenaline was 2.4 mM and for adrenaline 1.0 mM, and V 15.6 and 3.6 nmol/min per mg of microsomal protein respectively. Both catecholamines bound to the microsomal fraction, producing a type II spectral change, with a Ks for noradrenaline of 0.9 mM and for adrenaline of 1.0 mM, and showed other characteristics of type II compounds by inhibited the reduction of cytochrome P-450 by NADPH and exhibiting an enhanced metabolism in the presence of acetone. The major product of catecholamine metabolism was an as yet unidentified alkali-labile compound, which did not correspond to any of the recognized catecholamine metabolites. 相似文献
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G T Ankley R E Reinert A E Wade R A White 《Comp. Biochem. Physiol. C, Comp. Pharmacol. Toxicol.》1985,81(1):125-129
Bluegill (Lepomis macrochirus R.) were acclimated to 12, 22 or 32 degrees C for 5 or 14 days. Liver weight to body weight ratio and the rate of metabolism of benzo[alpha]pyrene by liver microsomes varied inversely with the acclimation temperature of the fish. Concentration of microsomal cytochrome P-450, as determined by CO-difference binding spectra, was not significantly affected by acclimation temperature. There were no qualitative or quantitative differences in the electrophoretic patterns of proteins with molecular weights similar to those reported for cytochrome P-450. There were no shifts in the temperature optima of the microsomal benzo[alpha]pyrene hydroxylase activity. 相似文献
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Interaction of oxygen and aromatic amines with hepatic microsomal mixed-function oxidase 总被引:2,自引:0,他引:2
P Hlavica 《Biochimica et biophysica acta》1972,273(2):318-327
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The composition and activity of the rat hepatic mixed-function oxidase system were investigated, in male rats 17 to 127 weeks old, with respect to content of its various components and their response to induction by phenobarbital and beta-naphthoflavone. There were decreases in many of the components of this enzyme system in older rats which could not be fully compensated by phenobarbital induction. However, there appeared to be no age-related loss of response to induction by beta-naphthoflavone. Decreases in mixed-function oxidase enzymes with age did not occur at the same rate or to the same extent. Metabolic studies with ethylmorphine and aniline demonstrated some age-associated changes which did not necessarily parallel reductions in the enzyme system. For example, there was a reduction in apparent Km as a function of age for the hydroxylation of aniline in rats treated with beta-naphthoflavone, even though they showed no apparent change in the amount of cytochrome P-450. There was also a trend to altered Km for the demethylation of ethylmorphine in saline or corn oil treated rats in older animals. We feel that these changes are a reflection of differential reductions in the various isoenzymes of cytochromes P-450. Further studies are planned to confirm this hypothesis. 相似文献
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J. J. Neal 《Entomologia Experimentalis et Applicata》1987,43(2):175-179
The maximum metabolic cost of microsomal mixed-function oxidase (MFO) induction was measured in terms of food utilization parameters. MFOs in larvae of Heliothis zea (Boddie) (Lepidoptera: Noctuidae) were induced by feeding on diet containing indole 3-carbinol (I3C). Growth, food utilization parameters, cytochrome P-450 content and O-demethylase activity of these larvae were compared to larvae reared on the same diet without I3C. Three-fold to nine-fold greater O-demethylase activity and seven-fold more cytochrome P-450 were measured in larvae fed I3C, but no differences were detected in the food utilization and growth parameters. These results do not support the view that costs of MFO induction may be responsible for differences in food utilization parameters.
Coûts métaboliques de l'induction de la fonction oxydase mixte chez Heliothis zea
Résumé Le coût métabolique maximum de l'induction de la fonction oxydase mixte microsomale (MFO) a été évalué au moyen de paramètres caractérisant l'utilisation de l'aliment. Les MFO des chenilles d' H. zea ont été induites en les élevant avec un régime contenant 0,2% d'indole 3-carbinol (I3C) en poids/poids humide. L'induction a été mise en évidence en mesurant l'O-deméthylation du pnitroanisole par les microsomes de l'intestin des larves des 4ème et 5ème stades, et la teneur en cytochrome P-450 (mesurée par les différences des spectres de l'oxyde de carbone) des microsomes de l'intestin des larves du 5ème stade élevées avec I3C et témoins. La digestibilité approchée, l'efficacité de la conversion de l'aliment digéré et l'efficacité de la conversion de l'aliment ingéré (évaluée d'après la durée de développement larvaire de la néonate à la prénymphe), le temps pour atteindre le stade prénymphe, le poids final, on été comparés chez les témoins et chez les chenilles élevées sur I3C. Les chenilles élevées sur I3C ont présenté une activité O-deméthylase 3 à 2 fois supérieure et 7 fois plus de cytochrome P-450, mais aucune différence n'a pu être décelée pour les paramètres d'utilisation alimentaire et de croissance. Ces résultats ne confirment pas l'hypothèse suivant laquelle le coût de l'induction de MFO pourraît être responsable de différences dans les paramètres de l'utilisation de l'aliment.相似文献
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In order to assess the role of ketone bodies in the diabetes-induced changes in hepatic mixed-function oxidase activity, rats rendered hyperketonaemic by dietary administration of medium chain triacylglycerols were compared with streptozotocin treated rats. Both groups of animals became hyperketonaemic but only the latter were hyperglycaemic. Treatment with streptozotocin or medium chain triacylglycerols gave rise to marked increases in the O-dealkylations of ethoxyresorufin, ethoxycoumarin and pentoxyresorufin, the p-hydroxylation of aniline and the N-demethylation of dimethylnitrosamine. It is concluded that the streptozotocin-induced changes in hepatic mixed-function oxidases are mediated, at least partly, by the high levels of ketone bodies. 相似文献
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Drug interactions in experimental hepatic porphyria. A model for the exacerbation by drugs of human variegate porphyria 总被引:3,自引:0,他引:3
F De Matteis 《Enzyme》1973,16(1):266-275
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Feeding of vitamin A-deficient diet to male weanling rats for 10 weeks resulted in significant decrease in the body weight and marked reduction in the hepatic vitamin A content. The levels of hepatic phase I microsomal enzymes cytochrome P-450, cytochrome b5, aminopyrine N-demethylase and arylhydrocarbon hydroxylase were found to be substantially reduced by vitamin A-deficiency. Also, the activity of phase II microsomal UDP - glucuronyl transferase enzyme was significantly decreased in deficient animals. Following repeated oral administration of DDT (15 mg/kg/body wt/day) for 21 days, the phase I microsomal enzymes were induced to a greater extent in controls as compared to deficient animals. UDP - glucuronyltransferase remained insensitive to DDT induction. The results imply that the capacity for induction of the hepatic mixed-function oxidase enzyme system is impaired in deficient animals concurrently exposed to DDT. 相似文献
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P. D. Siersema R. P. van Helvoirt M. I. Cleton-Soeteman W. C. de Bruijn J. H. P. Wilson H. G. van Eijk 《Biological trace element research》1992,35(1):65-72
Porphyria cutanea tarda (PCT) and experimental porphyria are characterized by a decreased activity of the enzyme uroporphyrinogen decarboxylase, and accumulation of uroporphyrins and heptacarboxylporphyrins in the liver. Iron (Fe) plays an important role in PCT and experimental porphyria. Biochemically and electron microscopically, we examined the relationship between Fe and porphyrins in liver tissue of C57BL/10 mice made porphyric by administration of iron dextran as Imferon® (IMF), and in liver biopsies of patients with symptomatic PCT. Accumulation of uroporphyrins and heptacarboxylporphyrins, and an increased amount of Fe were observed in livers of mice treated with IMF and in liver biopsies of patients with PCT. In mice treated with IMF, the activity of uroporphyrinogen decarboxylase was decreased. Both in livers of mice treated with IMF and in livers of patients with PCT, needle-like structures, representing uroporphyrin crystals, were observed by electron microscopy. Uroporphyrin crystals and Fe (as ferritin) were observed in the same hepatocyte. Moreover, there was a striking morphological correlation between uroporphyrin crystals and ferritin-Fe, suggesting a role for (ferritin-)Fe in the pathogenesis of porphyria. 相似文献
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S S Tong Y Hirokata M A Trush E G Mimnaugh E Ginsburg M C Lowe T E Gram 《Biochemical and biophysical research communications》1981,100(3):944-950
The photosystem II electron acceptor 3,6-dichloro-2,5-dimethoxy-p-benzoquinone [DCDMQ] is suggested to replace the second quinone-type two electron acceptor B (or R); the DCDMQ Hill reaction is sensitive to 3-(3,4-dichlorophenyl)-1,1-dimethylurea, but is insensitive to dry heptane extraction of thylakoids and other photosystem II inhibitors. Addition of HCO3? to CO2-depleted thylakoids in silicomolybdate, DCDMQ, diaminodurene and ferricyanide Hill reactions brought about 1,3,10 and 10 fold increase in the electron transport rates; these data confirm that HCO3? affects both Q? to B and B2? to PQ reactions. 相似文献
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M. A. Q. Khan R. I. Morimoto J. T. Bederka Jr. J. M. Runnels 《Biochemical genetics》1973,10(3):243-252
The microsomal mixed-function oxidase (MFO) in houseflies is controlled by two semidominant genes, Ox
2
and Ox
5
, situated on chromosomes 2 and 5, respectively. MFO controlled by these genes has almost similar affinity toward cyclodiene epoxidation, but only the one controlled by Ox
5
can degrade DDT. A strain, YFc, homozygous for both oxidase genes shows twice as much MFO activity toward aldrin as either of the parent homozygotes, Fc or Y, but only as much activity toward DDT as the parent strain Fc. These Ox
2
and Ox5 genes in the YFc strain maintain their identity with regard to DDT in their hybrids with a susceptible homozygous strain recessive for the two oxidases as seen by segregation in the test-cross progenies. The Ox
2
gene is situated at 32 units from the Deh and car genes, 40 units from stw, and about 69 units from Mk. The Ox
5
gene is situated at 40 units from the ocra gene and 82 units from apt on chromosome 5. 相似文献
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Abstract One group of biological tools that are useful for monitoring exposure to xenobiotics (and hence water quality) have been collectively referred to as biomarkers and are denned in this paper as any biochemical, histological and/or physiological alterations or manifestations of stress. Biomarkers within an aquatic toxicological context generally represent biological responses of individual organisms to xenobiotic exposure (i. e. responses at the whole organism level of biological organization). These include among others, enzyme alterations, bile metabolites, RNA/DNA ratio, adenylate energy charge, skeletal abnormalities, immune dysfunction, behavioural changes and histopathological lesions. Biomarkers can act as effective early warning sentinels to ensure the protection of the integrity of whole ecosystems, including freshwater and marine ecosystems. This paper briefly reviews a selection of fish biomarkers of xenobiotic chemical exposure and discusses their respective strengths and limitations for use in biomonitoring. An example of the application of fish mixed-function oxidase (MFO) and cytochrome P-450 as biomarkers of chemical exposure in Port Phillip Bay is provided. It is concluded that judicious application of biomarkers such as MFO in association with an understanding of the underlying causal mechanisms of induction and toxicity, will contribute to the successful prediction of biological effects of xenobiotic exposure on fish population health. 相似文献