POLYMORPHIC N-ACETYLATION OF PHENELZINE AND MONOACETYLHYDRAZINE BY HIGHLY PURIFIED RABBIT LIVER ISONIAZID N-ACETYLTRANSFERASE

  • 1 January 1982
    • journal article
    • research article
    • Vol. 10  (3) , 225-229
Abstract
Two hydrazines of clinical interest, the antidepressant drug phenelzine (PHZ) and the hepatotoxic metabolite of [the tuberculostatic agent] isoniazid, monoacetylhydrazine (MAH), were polymorphically acetylated by highly purified preparations of rabbit liver N-acetyltransferase (NAT; EC 2.3.1.5). Both PHZ and MAH NAT activities exhibited purification and heat inactivation characteristics indistinguishable from genetically polymorphic NAT. Lineweaver-Burk analyses of PHZ and MAH NAT activities yielded apparent KM values of 4.18 mM for PHZ and 1.28 mM for MAH. These findings have implications concerning the structural requirements for polymorphic N-acetylation by liver NAT, and suggest that a wide variety of hydrazine compounds are also polymorphically N-acetylated.