Fig 1.

INH metabolism in mammals and mycobacteria. In mammals (left of the dashed line), N-acetyl isoniazid is the most abundant INH metabolite and undergoes hydrolysis, producing isonicotinic acid and acetylhydrazine. Isonicotinic acid and oxoacid hydrazones are also formed directly from INH. Isonicotinic acid conjugates to other molecules, such as glycine. Acetylhydrazine undergoes rapid acetylation to produce diacetylhydrazine or cleavage, yielding ammonia. The boxed metabolites are the major products found in mammals. In M. tuberculosis (right of the dashed line), INH undergoes oxidative activation by KatG, and the resulting isonicotinyl radical forms adducts with NAD⁺.