Partial purification and properties of the isoniazid transacetylase in human liver. Its relationship to the acetylation of p-aminosalicylic acid.

Abstract

A soluble enzyme is described in human post-mortem liver and small intestinal mucosa that is believed responsible for the heritable differences in acetylation of isonicotinic acid hydrazide (INH, isoniazid). The enzyme was partially purified (300-fold). Its affinity for INH was about 10 times that for p-aminosalicylic acid (PAS). PAS and hydralazine inhibited INH acetylation competitively, the latter over 100 times as strongly as PAS. No acetylation of p-nitroaniline was detected. From livers representative of the "rapid" and "slow" groups, concentrated preparations of the enzyme showed no difference in apparent Michaelis constant for INH and, in several other respects, the enzymes behaved identically. The differences in activity of these groups did not appear to be due to differences in enzyme affinity for INH. Excretion of free and acetylated PAS in the urine of rapid and slow inactivators of INH did not show acetylation differences. Although some overlap probably exists, there appear to be 2 acetylation pathways available in man, 1 with widely differing acetylation capacities utilized by INH and certain polycyclic amines, and another with uniform capacity utilized by simple aromatic amines.