[Interaction of the Cu(Lys)2 complex with the NADPH-dependent microsomal electron transport system and microsomal membrane].
The low molecular weight analog of superoxide dismutase, th Cu(Lys)2 complex inhibits the oxidation of type I (piperidinoanthraquinone) and type II(aniline) substrates catalyzed by cytochrome P-450. This fact is not associated with the conversion of cytochrome P-450 into the inactive form--cytochrome P-420. It was shown that the method of determining the activity of NADPH-cytochrome c-reductase by the cytochrome c reduction rate cannot be employed in the presence of the Cu(Lys)2 and Cu(Tyr)2 complexes. Potassium ferricyanide was used to demonstrate that Cu(Lys)2 does not affect the NADPH-cytochrome c-reductase activity. The inhibiting effect of Cu(Lys)2 on the microsomal oxidation of the substrates does not result from the interaction of the complex with the components of the NADPH-dependent microsomal electron transport system. The effect observed can be accounted for by the dismutase-like action of the complex on the superoxide radicals generated during the microsomal oxidation of the substrates. The interaction of Cu(Lys)2 with the membrane was studied by the ESR method using stable nitroxide rabicais. It was shown that the complex cannot freely diffuse through the lipid bilayer membrane. A model for Cu(Lys)2 incorporation into the membrane is proposed.
D000818:Animals; D003300:Copper; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008051:Lipid Bilayers; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000378:metabolism
D008051:Lipid Bilayers; D003300:Copper; D003577:Cytochrome P-450 Enzyme System; D013482:Superoxide Dismutase; D009251:NADPH-Ferrihemoprotein Reductase; D008239:Lysine
Vzaimodeĭstvie kompleksa Cu(Lys) 2 a NADPH-zavisimoĭ mikrosomal'noĭ tsep'iu perenosa élektronov i mikrosomal'noĭ membranoĭ.