Cytochrome P-450 dependent deethylase activity in rat and hairless mouse skin microsomes. 1982

S J Moloney, and J M Fromson, and J W Bridges

Microsomal fractions were prepared from rat and hairless mouse skin. The method of preparation was validated by studying the distribution of succinate dehydrogenase, acid phosphatase and UDP-glucuronosyltransferase. Induction of oxidative deethylation activities by 5,6-benzoflavone and 3-methylcholanthrene was investigated. Preparations from hairless mouse skin exhibited higher basal activities but the enzymes were less responsive than those of rat skin to inducers. Species differences were observed in the extent of induction between topical and i.p. administration of 5,6-benzoflavone, the former route being more effective in the hairless mouse and the latter route most effective in the rat. Generally oxidative deethylation activity increased linearly with protein concn up to 2-3 mg protein/ml. The only exception was rat skin microsomes prepared from animals pretreated with 5,6-benzoflavone, where linearity was observed only to 0.75 mg protein/ml above which oxidative deethylation activity decreased with increasing protein concn. The inhibition of 7-ethoxycoumarin deethylase by various compounds was investigated; the activity in hairless mouse skin exhibited a greater sensitivity to water-soluble solvents than that in rat skin microsomes. Both hairless mouse and rat skin 7-ethoxycoumarin deethylase were sensitive to inhibition by 5,6-benzoflavone, 7,8-benzoflavone and metyrapone.

UI MeSH Term Description Entries
D008812 Mice, Hairless Mutant strains of mice that produce little or no hair. Hairless Mice,Mice, Inbred HRS,Mice, hr,Hairless Mouse,Mice, HRS,Mouse, HRS,Mouse, Inbred HRS,HRS Mice,HRS Mice, Inbred,HRS Mouse,HRS Mouse, Inbred,Inbred HRS Mice,Inbred HRS Mouse,Mouse, Hairless
D008861 Microsomes Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed) Microsome
D010088 Oxidoreductases The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9) Dehydrogenases,Oxidases,Oxidoreductase,Reductases,Dehydrogenase,Oxidase,Reductase
D010105 Oxygenases Oxidases that specifically introduce DIOXYGEN-derived oxygen atoms into a variety of organic molecules. Oxygenase
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D003577 Cytochrome P-450 Enzyme System A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism. Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001571 Benzoflavones Organic compounds containing a BENZENE ring attached to a flavone group. Some of these are potent arylhydrocarbon hydroxylase inhibitors. They may also inhibit the binding of NUCLEIC ACIDS to BENZOPYRENES and related compounds. The designation includes all isomers; the 7,8-isomer is most frequently encountered. Benzoflavone Compounds,Compounds, Benzoflavone
D012867 Skin The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
D015660 7-Alkoxycoumarin O-Dealkylase A drug-metabolizing enzyme found in the hepatic, placental and intestinal microsomes that metabolizes 7-alkoxycoumarin to 7-hydroxycoumarin. The enzyme is cytochrome P-450- dependent. 7-Ethoxycoumarin O-Dealkylase,7-Ethoxycoumarin O-Deethylase,7-Ethoxycoumarin Dealkylase,7-Ethoxycoumarin Hydroxylase,7-Ethoxycoumarin Monooxygenase,7-Ethoxycoumarin O-De-Ethylase,7-Propoxycoumarin O-Depropylase,Cytochrome P-450-Dependent O-Dealkylase,Ethoxycoumarin Deethylase,Ethoxycoumarin O-Deethylase,7 Alkoxycoumarin O Dealkylase,7 Ethoxycoumarin Dealkylase,7 Ethoxycoumarin Hydroxylase,7 Ethoxycoumarin Monooxygenase,7 Ethoxycoumarin O De Ethylase,7 Ethoxycoumarin O Dealkylase,7 Ethoxycoumarin O Deethylase,7 Propoxycoumarin O Depropylase,Cytochrome P 450 Dependent O Dealkylase,Dealkylase, 7-Ethoxycoumarin,Deethylase, Ethoxycoumarin,Ethoxycoumarin O Deethylase,Hydroxylase, 7-Ethoxycoumarin,Monooxygenase, 7-Ethoxycoumarin,O-Deethylase, 7-Ethoxycoumarin,O-Depropylase, 7-Propoxycoumarin,P-450-Dependent O-Dealkylase, Cytochrome

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