Spin state control of cytochrome P-450 reduction and catalytic activity in a reconstituted P-450 LM2 system as induced by a series of benzphetamine analogues.
Reconstituted liposomal cytochrome P-450 LM2 was reacted with a series of benzphetamine analogues as substrates. Based on the thermodynamical model of Ristau et al. (Biochim. Biophys. Acta, 536 (1978) 226-234) the free enthalpy of substrate binding to the high spin form of the enzyme was shown to correlate with the total high spin content of the respective enzyme substrate complex. Reduction and substrate N-demethylation rates as well have been evidenced to linearly correlate with the substrate-induced spin shift delta alpha and moreover with the spin content alpha. The data obtained provide further experimental support for the spin state regulation of the reduction and conversion rate of cytochrome P-450 LM2.
D000818:Animals; D001589:Benzphetamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D008297:Male; D008433:Mathematics; D008862:Microsomes, Liver / Q000201:enzymology*; D008956:Models, Chemical; D009245:NADH Dehydrogenase / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats
D010627:Phenethylamines; D001589:Benzphetamine; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D009245:NADH Dehydrogenase