Localization of the active center of microsomal cytochrome P-450.
To solve the problem of localization of the active center of cytochrome P-450 in microsomal membranes, new bifunctional compounds (I-IV), which contain pyridine radical, aliphatic chain of variable length and diphosphonic acid ("floating" molecules) have been applied. These compounds inhibit oxidation and binding of the substrates of cytochrome P-450 (aminopyrine and aniline), inhibition being of a competitive character. Measurements of distribution coefficients between water and membranes of microsomes and liposomes from egg phosphatidylcholine evidence that the microsomal proteins are necessary for providing effective interaction of I-IV with microsomal membrane. The 1H-NMR method has demonstrated compounds to be incorporated into lipid bilayer so that the non-polar part is in the inner membrane volume. The results obtained confirm our previous conclusion (Krainev A.G., Weiner L.M., Alferyev I.S., Slynko N.M. (1985) Biochim. Biophys. Acta, 818, 96-104) about localization of the active center of microsomal cytochrome P-450 at the depth of approximately 18 A from the hydrophilic surface of a membrane.
Krainev
A G
AG
Institute of Chemical Kinetics and Combustion, Novosibirsk, U.S.S.R.
Weiner
L M
LM
Alferyev
I S
IS
Mikhalin
N V
NV
D000632:Aminopyrine / Q000378:metabolism; D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents / Q000378:metabolism / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007425:Intracellular Membranes / Q000201:enzymology; D008081:Liposomes / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008862:Microsomes, Liver / Q000201:enzymology*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013053:Spectrophotometry; D013329:Structure-Activity Relationship
D000814:Aniline Compounds; D003432:Cross-Linking Reagents; D065607:Cytochrome P-450 Enzyme Inhibitors; D008081:Liposomes; D000632:Aminopyrine; D003577:Cytochrome P-450 Enzyme System; C023650:aniline