Acetylation

NAT2 codes for N-acetyltransferase 2, the liver enzyme that attaches acetyl groups to drugs, toxins, and dietary compounds for clearance. The variants produce one of the most dramatic phenotypic splits in pharmacogenomics: "slow acetylators" and "fast acetylators" handle the same compounds at very different speeds.

Roughly 50–60% of people of European descent are slow acetylators (carriers of two reduced-activity NAT2 alleles). Carriers of the slow phenotype are associated with longer drug exposure, increased side effects from medications like isoniazid (TB drug), hydralazine, and sulfa antibiotics, and slower clearance of dietary aromatic amines from grilled meats and tobacco smoke. Fast acetylators clear these compounds rapidly.

Cigarette smoke, well-done grilled or charred meat, and certain occupational exposures all run through NAT2-dependent clearance. Antioxidant-rich foods support the broader detox network around acetylation. Alpha-lipoic acid and NAC offer indirect support. Pacing drug doses and timing meals can both reduce the slow-acetylator burden.

A "this medication hits me harder than it should" or "smoke really bothers me" pattern often hides a slow-acetylator NAT2 genotype. Which version you carry decides how you read drug response, why certain dietary or environmental exposures land harder, and which clearance support is worth maintaining.