Biomaterial Database

On the inhibition of microsomal drug metabolism by polychlorinated biphenyls (PCB) and related phenolic compounds. 1977

A Schmoldt, and W Herzberg, and H F Benthe

The in vitro metabolism of p-nitroanisole, aminopyrine, and aniline by rat liver microsomal monoxygenases were studied in the presence of different polychlorinated biphenyl (PCB) mixtures and some related hydroxybiphenyls. The tested PCB mixtures contained preferably dichloro- (di-CB), tetrachloro- (tetra-CB), or hexachlorobiphenyls (hexa-CB). All PCB were competitive inhibitors of only aminopyrine demethylation by normal microsomes (Ki 22-39 micron). In microsomes of PCB-pretreated rats the aminopyrine demethylation was inhibited noncompetitively by di-CB and hexa-CB whereas tetra-CB remained a competitive inhibitor (Ki 12 micron). Moreover, after PCB pretreatment all PCB were competitive inhibitors of p-nitroanisole demethylation. 2-OH-biphenyl and 4-OH-biphenyl caused competitive inhibition of aminopyrine demethylation and aniline hydroxylation but failed to inhibit p-nitroanisole metabolism by normal microsomes. Chlorinated 4-hydroxybiphenyls inhibited competitively the metabolism of both type I and type II substrates. However, after PCB pretreatment all phenolic compounds caused uncompetitive inhibition of aniline hydroxylation.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008297	Male		Males
D008862	Microsomes, Liver	Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.	Liver Microsomes,Liver Microsome,Microsome, Liver
D009251	NADPH-Ferrihemoprotein Reductase	A flavoprotein that catalyzes the reduction of heme-thiolate-dependent monooxygenases and is part of the microsomal hydroxylating system. EC 1.6.2.4.	Cytochrome P-450 Reductase,Ferrihemoprotein P-450 Reductase,NADPH Cytochrome P-450 Oxidoreductase,NADPH Cytochrome P-450 Reductase,NADPH Cytochrome c Reductase,Cytochrome P-450 Oxidase,Cytochrome P450 Reductase,Ferrihemoprotein P450 Reductase,NADPH Cytochrome P450 Oxidoreductase,NADPH Cytochrome P450 Reductase,NADPH-Cytochrome P450 Reductase,NADPH-P450 Reductase,Cytochrome P 450 Oxidase,Cytochrome P 450 Reductase,Ferrihemoprotein P 450 Reductase,NADPH Cytochrome P 450 Oxidoreductase,NADPH Cytochrome P 450 Reductase,NADPH Ferrihemoprotein Reductase,NADPH P450 Reductase,Oxidase, Cytochrome P-450,P-450 Oxidase, Cytochrome,P450 Reductase, Cytochrome,P450 Reductase, NADPH-Cytochrome,Reductase, Cytochrome P-450,Reductase, Cytochrome P450,Reductase, Ferrihemoprotein P-450,Reductase, Ferrihemoprotein P450,Reductase, NADPH-Cytochrome P450,Reductase, NADPH-Ferrihemoprotein,Reductase, NADPH-P450
D009575	Nitroanisole O-Demethylase	Oxidative enzyme which transforms p-nitroanisole into p-nitrophenol.	Nitroanisole O Demethylase,Demethylase, Nitroanisole O,O Demethylase, Nitroanisole,O-Demethylase, Nitroanisole
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
D010636	Phenols	Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.
D011078	Polychlorinated Biphenyls	Industrial products consisting of a mixture of chlorinated biphenyl congeners and isomers. These compounds are highly lipophilic and tend to accumulate in fat stores of animals. Many of these compounds are considered toxic and potential environmental pollutants.	PCBs,Polychlorinated Biphenyl,Polychlorobiphenyl Compounds,Biphenyl, Polychlorinated,Biphenyls, Polychlorinated,Compounds, Polychlorobiphenyl
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