Correlations between spin equilibrium shift, reduction rate, and N-demethylation activity in liver microsomal cytochrome P-450 and a series of benzphetamine analogues as substrates.
Cytochrome P-450 forms a thermal ferric spin equilibrium which is significantly shifted by substrate binding. Within a series of benzphetamine analogues the liver microsomal enzyme system exhibits a close correlation of the substrate induced spin equilibrium shift towards the high spin state and both the rate of P-450 reduction, and of substrate turnover, as well. The spin equilibrium regulates the first electron transfer by favoured high spin state reduction and rapid pre-equilibration with respect to the low spin fraction.
D000818:Animals; D001589:Benzphetamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D003577:Cytochrome P-450 Enzyme System / Q000302:isolation & purification*; D004579:Electron Transport; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D010084:Oxidation-Reduction / Q000187:drug effects; D010089:Oxidoreductases, N-Demethylating / Q000302:isolation & purification*; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013053:Spectrophotometry; D013379:Substrate Specificity
D010627:Phenethylamines; D001589:Benzphetamine; D003577:Cytochrome P-450 Enzyme System; D010089:Oxidoreductases, N-Demethylating