Isoprene metabolism by liver microsomal mono-oxygenases

Abstract

1. 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.

2. 3,4-Epoxy-3-methyl-1-butene was the major metabolite of isoprene, and the kinetic constants (K_m and V_max) 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. 3,4-Epoxy-2-methyl-1-butene was epoxidated further to the mutagenic isoprene dioxide by microsomes from control or pretreated mice. The K_m and V_max were determined and phenobarbital shown to be an inducer of this epoxidation.