GENETIC CONTROL AND ISOZYMIC COMPOSITION OF DRUG ACETYLATING ENZYMES

ABSTRACT . Observations in families of slow and rapid isoniazid acetylator rabbits indicate the existence of a new drug acetylating polymorphism in this species. Crosses between rabbits of both isoniazid acetylator phenotypes show that the variation in p-aminobenzoic acid (PABA) Nacetyltransferase (NAT) activity in peripheral blood is genetically determined and controlled by a pair of allelic autosomal genes. The regulatory systems controlling the enzymes for PABA acetylation in blood and isoniazid acetylation in liver are interdependent since the highest blood PABA NAT activities are associated with the lowest liver isoniazid NAT activities, and vice versa. Comparisons of isozyme patterns and other biochemical properties of partially purified NAT'S from blood and liver indicate that NAT from slow isoniazid acetylator liver and NAT's from blood of both acetylator phenotypes may possess certain structural features in common. The isozyme pattern and biochemical characteristics of NAT from rapid isoniazid acetylator liver differ from those of either slow isoniazid acetylator NAT or blood NAT. The possible significance of these findings to the evolutionary origin of drug acetylating enzymes in rabbit blood and liver is discussed.