[Inhibition of the dealkylating activity of cytochrome P-450 isoforms in rat liver microsomes by the products of phospholipase A2-induced phospholipid hydrolysis].
The effects of exogenous phospholipase A2, oleic acid and lysolecithines on oxidative NADPH-dependent O-dealkylation of 7-ethoxycumarin in liver microsomes of phenobarbital- and 3-methylcholanthrene-induced and non-induced rats were studied. Oleic acid up to the concentration of 100 micrograms/mg of protein did not inhibit this process. gamma-Myristoyl and gamma-palmitoyl lysolecithines decreased the reaction rate already at concentrations of 2-4 micrograms/mg of protein. Oleic acid was attached to cytochrome P-450 according to type I binding, whereas lysolecithines did not bind to the cytochrome. Thus, in the presence of phospholipase A2 in liver microsomes of non-induced rats, when the phospholipid hydrolysis products are accumulated at low concentrations, 7-ethoxycumarin deethylase is inhibited by lysophospholipids but not by free fatty acids. In 3-methylcholanthrene-induced microsomes the sensitivity of O-deethylation of 7-ethoxycumarin to the inhibiting effect of phospholipase A2 or lysolecithine is lower than that in non-induced or phenobarbital-induced microsomes.
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D003640:Dealkylation; D004790:Enzyme Induction; D006868:Hydrolysis; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism; D010105:Oxygenases / Q000037:antagonists & inhibitors; D010740:Phospholipases / Q000494:pharmacology*; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats
D065607:Cytochrome P-450 Enzyme Inhibitors; D007527:Isoenzymes; D010743:Phospholipids; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2
Ingibirovanie dealkiliruiushcheĭ aktivnosti izoform tsitokhroma P-450 v mikrosomakh pecheni krysy produktami gidroliza fosfolipidov fosfolipazoĭ A2.