RT Journal Article
SR Electronic
T1 Polymorphic N-acetylation of phenelzine and monoacetylhydrazine by highly purified rabbit liver isoniazid N-acetyltransferase.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 225
OP 229
VO 10
IS 3
A1 D W Hein
A1 W W Weber
YR 1982
UL http://dmd.aspetjournals.org/content/10/3/225.abstract
AB Two hydrazines of clinical interest, the antidepressant drug phenelzine (PHZ) and the hepatotoxic metabolite of isoniazid, monoacetylhydrazine (MAH), were shown to be polymorphically acetylated by highly purified preparations of rabbit liver N-acetyltransferase (NAT). 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.