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.

ABSTRACT

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.