Isoprene metabolism by liver microsomal mono-oxygenases

Abstract

Mouse-liver microsomal mono-oxygenases metabolize isoprene to the corresponding mono-epoxides. The reaction was NADPH- and O2-dependent and was inhibited by CO, SKF525-A and metyrapone. 3,4-Epoxy-3-methyl-1-butene was the major metabolite of isoprene, and the kinetic constants (Km and Vmax) for this epoxidation were determined by analysing the corresponding diol by g.l.c. in incubations with microsomes from control or pretreated mice. 3,4-Epoxy-2-methyl-1-butene was a minor metabolite (approx. 20%). 3,4-Epoxy-2-methyl-1-butene was epoxidated further to the mutagenic isoprene dioxide by microsomes from control or pretreated mice. The Km and Vmax were determined and phenobarbital shown to be an inducer of this epoxidation.