Kinetic studies on benzene metabolism in rat liver--possible presence of three forms of benzene metabolizing enzymes in the liver.

The effects of food deprivation, ethanol consumption and phenobarbital (PB) administration on in vitro benzene metabolism in rat liver were studied by using benzene concentration ranging from 0.0055 to 6.25 mM. The kinetic analysis suggested that the liver of normally-fed rats contained two forms of benzene hydroxylases each with a Km value of 0.01 mM or 0.07 mM. The isozyme with a Km of 0.01 mM disappeared following one-day food deprivation, but the deprivation enhanced the activity of the other isozyme. Ethanol treatment markedly increased the activity of both normally-existing enzymes. On the other hand, PB treatment induced the synthesis of another benzene-metabolizing enzyme with a high Km value of 4.5 mM, the presence of which was indistinct in normal rats. The treatment had no influence on the activity of either of the normally-occurring low-Km isozymes. The combined effects of PB with food deprivation were additive, suggesting that the induction of low- and high-Km isozymes is each independent of the other.