PT  - JOURNAL ARTICLE
AU  - D W Hein
AU  - W G Kirlin
AU  - R J Ferguson
AU  - W W Weber
TI  - Biochemical investigation of the basis for the genetic N-acetylation polymorphism in the inbred hamster.
DP  - 1985 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 358--364
VI  - 234
IP  - 2
4099  - http://jpet.aspetjournals.org/content/234/2/358.short
4100  - http://jpet.aspetjournals.org/content/234/2/358.full
SO  - J Pharmacol Exp Ther1985 Aug 01; 234
AB  - Cytosolic acetyl coenzyme A-dependent N-acetyltransferase enzyme (E.C. 2.3.1.5) from inbred hamsters of each acetylator genotype was partially purified by ion-exchange chromatography. Two distinct N-acetyltransferase enzymes were identified; the first one exhibited a polymorphic expression across acetylator genotypes whereas the second exhibited a monomorphic expression. The monomorphic enzyme had consistently high isoniazid and procainamide N-acetyltransferase activity in homozygous rapid acetylator (Bio. 87.20), homozygous slow acetylator (Bio. 82.73/H), obligate heterozygous rapid acetylator F1 progeny and in each of the three acetylator genotypes of F2 progeny. In contrast, the polymorphic enzyme exhibited marked acetylator genotype-dependent N-acetyltransferase activity. High p-aminobenzoic acid N-acetyltransferase activity was exhibited in the homozygous rapid acetylator parental and F2 generation progeny, intermediate activity was exhibited in the heterozygous rapid acetylator F1 and F2 generation progeny and very low or nondetectable activity was exhibited in homozygous slow acetylator parental and F2 generation progeny. A similar gene dose-response relationship was exhibited by the polymorphic N-acetyltransferase enzyme toward isoniazid and procainamide. These results provide new insight into the biochemical basis for the substrate-dependent polymorphic and monomorphic expression of N-acetylation capacity in the inbred hamster.