The induction of cytochrome P450 isoform, CYP4A1, by clofibrate coincides with activation of ethanolamine-specific phospholipid base exchange reaction in rat liver microsomes. 1998

J Lenart, and I Komańska, and R Jasińska, and S Pikuła
Department of Cellular Biochemistry, M. Nencki Institute of Experimental Biology, Warsaw, Poland.

Administration of a hypolipidaemic drug, clofibrate, to rats resulted, 24 h after a single intraperitoneal injection (250 mg/kg body weight), in pronounced enhancement of the rate of phosphatidylethanolamine (PE) synthesis via the PE-specific base exchange (PEBE) reaction in liver microsomes. This was accompanied by 3.4-fold activation of microsomal omega-hydroxylation of lauric acid by cytochrome P450 4A1 isoform (CYP4A1) and an increase in the protein content of this isoform in endoplasmic reticulum (ER) membranes. Since PE represents a class of phospholipids (PL) prerequisite for proper functioning of CYP4A1, and the PEBE reaction is an inducible pathway of PL synthesis in hepatocytes under metabolic stress, one may speculate that this reaction is switched on when extensive remodelling of PL molecular species or/and massive synthesis of lipid bilayer components for membrane assembly is required.

UI MeSH Term Description Entries
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
D010714 Phosphatidylethanolamines Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to an ethanolamine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and ethanolamine and 2 moles of fatty acids. Cephalin,Cephalins,Ethanolamine Phosphoglyceride,Ethanolamine Phosphoglycerides,Ethanolamineglycerophospholipids,Phosphoglyceride, Ethanolamine,Phosphoglycerides, Ethanolamine
D002994 Clofibrate A fibric acid derivative used in the treatment of HYPERLIPOPROTEINEMIA TYPE III and severe HYPERTRIGLYCERIDEMIA. (From Martindale, The Extra Pharmacopoeia, 30th ed, p986) Athromidin,Atromid,Atromid S,Clofibric Acid, Ethyl Ester,Ethyl Chlorophenoxyisobutyrate,Miscleron,Miskleron,Chlorophenoxyisobutyrate, Ethyl
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
D004790 Enzyme Induction An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. Induction, Enzyme
D006899 Mixed Function Oxygenases Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation. Hydroxylase,Hydroxylases,Mixed Function Oxidase,Mixed Function Oxygenase,Monooxygenase,Monooxygenases,Mixed Function Oxidases,Function Oxidase, Mixed,Function Oxygenase, Mixed,Oxidase, Mixed Function,Oxidases, Mixed Function,Oxygenase, Mixed Function,Oxygenases, Mixed Function
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
D000960 Hypolipidemic Agents Substances that lower the levels of certain LIPIDS in the BLOOD. They are used to treat HYPERLIPIDEMIAS. Antihyperlipidemic,Antilipemic,Antilipemic Agents,Antilipemic Drug,Hypolipidemic Agent,Hypolipidemic Drug,Antihyperlipemics,Antihyperlipidemics,Antilipemic Drugs,Antilipemics,Hypolipidemic Drugs,Agent, Hypolipidemic,Agents, Antilipemic,Agents, Hypolipidemic,Drug, Antilipemic,Drug, Hypolipidemic,Drugs, Antilipemic,Drugs, Hypolipidemic
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats

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