Irene B. Glowinski

METABOLISM OF ARYLAMINES: EVIDENCE FOR COMMON GENETIC CONTROL OF ARYLHYDROXAMIC ACID ACYLTRANSFERASE (AHAT) AND GENETICALLY POLYMORPHIC N-ACETYLTRANSFERASE (NAT) OF RABBIT LIVER1

Publisher Summary Rabbit and human liver N-acetyltransferase acetylate certain carcinogenic arylamines, such as aminofluorene (AF) and benzidine, and drug substrates, such as isoniazid and sulfamethazine (SMZ). In these species, there are large differences in the rates of acetylation of these compounds and individuals can be classified as either rapid or slow acetylators. Such compounds are termed polymorphic substrates. Genetic differences in the rate of N-acetylation are associated with individual susceptibility to toxicity from chronic administration of drugs such as isoniazid. N-Acetylation may be important in the metabolic activation of certain arylamines and may be regarded as an initial step in this pathway. N-Hydroxylation of the corresponding amide occurs in many species in vitro and in vivo. Enzyme activity has been found in several rat tissues that are susceptible to the induction of tumors by 2-acetylaminofluorene (AAF). Many similarities between arylhydroxamic acid acyltransferase (AHAT) and N-acetyltransferase (NAT) exist with respect to biochemical parameters, isolation and purification, tissue distribution, and species variation. This chapter presents evidence for common genetic control of these two enzymes in rabbit liver and for the possibility of their identity.