Kinetic investigations of liver microsomal esterases with oxazepam esters.

Hepatic microsomal esterases of the mouse responsible for the bioactivation of inactive (prodrug) esters of the centrally acting oxazepam were studied. The enzymes are situated on the cytoplasmic side of the microsomes. The esterases are partly solubilized and partly inactivated by homogenization in aqueous glycerol and treatment with deoxycholate. There is good correlation between the rates of hydrolysis and steric constants of the acyl moiety. Substrate binding increases to an optimum with the number of carbon atoms in the acyl moiety and is of hydrophobic nature. An attempt has been made to classify the esterases on the basis of the effect of inhibitors and activators.