Abstract
Hepatic aldehyde oxidases from rabbit, mouse, rat, and guinea pig have been purified 10-fold to 15-fold and shown to catalyze the oxidation of methotrexate to 7-hydroxymethotrexate. The mouse and rat liver enzymes, however, were unable to catalyze the oxidation of the related compound aminopterin, and the aminopterinoxidizing ability of the rabbit liver enzyme was much inferior to its methoxtrexateoxidizing ability. The oxidase from all four species was stimulated by ammonium ion and inhibited by menadione; species differences were noted, however, in pH optima and susceptibility to inhibition by Triton X-100. The results support the hypothesis that, in some species, the greater toxicity of aminopterin (as compared with that of methotrexate) is attributable to the lesser ability of aminopterin to serve as a substrate for hepatic aldehyde oxidase.