Isoniazid is an antibiotic drug used to treat tunerculosis, as well as other types of mycobacteria. Through a currently unknown reaction that may be spontaneous or enzymatic, pyruvic acid or oxoglutaric acid can undergo a dehydration reaction with isoniazid, forming isoniazid pyruvate or isoniazid alpha-ketoglutaric acid. Isoniazid may also react with hydrogen peroxide in the lysosome, forming an isonicotinoyl radical catalyzed by myeloperoxidase. The isonicotinoyl radical can then have either NAD or NADP added in a non-enzymatic reaction, forming isonicotinoyl-NAD and NADP adducts. Isoniazid can have an acetyl group added to it by arylamine N-acetyltransferase 2, fvorming acetylisoniazid. This can then enter the endoplasmic reticulum and, with the addition of a water molecule, can form isonicotinic acid and acetylhydrazine. Isoniazid can also be converted to hydrazine and isonicotinic acid via the same reaction, and the hydrazine can have an acetyl group added to it by arylamine N-acetyltransferase 2 in order to form acetylhydrazine. Acetylhydrazine can have another acetyl group added to it by arylamine N-acetyltransferase 2 to form diacetylhydrazine which is then excreted. It can alternatively be processed by cytochrome P450 2E1 into hepatotoxins, which are then joined to glutatione by glutatione S-transferase omega-2 to form R-S-glutatione, which is then excreted. Finally, isonicotinic acid can react with a glycine in an unclear reaction, potentially requiring ATP and coenzyme A and forming an intermediate, producing isonicotinylglycine, which is also excreted.

Isoniazid Metabolism References