Properties and inhibition of rat malathion carboxylesterases.

Two malathion carboxylesterase fractions, designated as esterase fraction A and esterase fraction B, that hydrolyze malathion were purified 13- and 18-fold, respectively, from rat liver microsomes. The two enzymes could not be distinguished kinetically, but fraction A contained at least one electrophoretic species not present in fraction B. The molecular weight of fraction A was estimated as 50,000-60,000; the molecular weight of fraction B was about twice this value. Incubation of [methoxy-14C]malathion with fraction A or fraction B resulted in a mixture of malathion alpha and beta monoacids, but the composition of the mixture produced by fraction A (alpha/beta = 1.5) differed from that produced by fraction B (alpha/beta = 0.2), indicating the presence of multiple species of carboxylesterases in mammalian liver microsomes. Isomalathion was substantially more potent as an inhibitor of both rat liver and rat serum malathion carboxylesterases than O,S,S-trimethyl phosphorodithioate. Isomalathion appeared to be equipotent in inhibiting the rat liver carboxylesterase-catalyzed reactions leading to either alpha or beta-monoacid. O,S,S-Trimethyl phosphorodithioate, on the other hand, preferentially diminished the reactions leading to alpha monoacid. In contrast, the rat serum carboxylesterase-catalyzed reactions leading to either alpha or beta monoacid were inhibited to approximately on equal degree by isomalathion and O,S,S-trimethyl phosphorodithioate.