Phenomenon of activation of cytochrome P450 by nonionic detergents.
Mechanism of substitution of nonionic detergent Emulgen 913 for phospholipid as an activator of N-demethylase activity of cytochrome P450 form 2B4 (LM(2)) has been studied. It is shown that such an activation takes place at the detergent concentrations below values critical for micelle formation. Under these conditions, Emulgen does not affect the hexameric state of the cytochrome. The stimulating effect proved to be similar in reconstituted monooxygenase systems containing (a) cytochrome P450 2B4 and NADPH-cytochrome P-450 reductase and (b) cytochrome 2B4 and organic hydroperoxides. These results indicate that the activation is due to an effect of the detergent upon P450 2B4 per se rather than upon P450/flavoprotein complex formation. The above conclusion is supported by the sedimentation data and measurement of the CD spectra of cytochrome P450 2B4 at 380-450 nm.
Myasoedova
Ksenia N
KN
Department of Kinetics and Catalysis, N.N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Kosygina Str. 4, 119991 Moscow, Russia. skulach@belozersky.msu.ru
Arutyunyan
Alexandr M
AM
Magretova
Natalya N
NN
D000818:Animals; D002942:Circular Dichroism; D003577:Cytochrome P-450 Enzyme System / Q000302:isolation & purification / Q000378:metabolism*; D003902:Detergents / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D010743:Phospholipids / Q000737:chemistry*; D011506:Proteins / Q000032:analysis; D011817:Rabbits
D003902:Detergents; D010743:Phospholipids; D011506:Proteins; D003577:Cytochrome P-450 Enzyme System; D010089:Oxidoreductases, N-Demethylating