Hepatic manifestations of non-steroidal inflammatory bowel disease therapy

Figure 1 Azathioprine/6-mercaptopurine metabolism. Azathioprine is converted to 6-MP via nonenzymatic reactions. IMPDH and GMPS generate active 6-thioguanine nucleotides. TPMT results in the production of hepatotoxic 6-MMP and 6-MMPR metabolites. 6-MP: 6-mercaptopurine; TPMT: Thiopurine methyltransferase; XO: Xanthine oxidase; HPRT: Hypoxanthineguanine-phosphoribosyl-transferase; 6-MMP: 6-methylmercaptopurine; 6-MMPR: 6-methylmercaptopurine ribonucleotide; IMPDH: Inosine monophosphate dehydrogenase; GMPS: Guanosine monophosphate synthetase; MPK: Monophosphate kinase; DPK: Diphosphate kinase. Adapted from Cuffari C, Theoret Y, Latour S, Seidman G. 6-Mercaptopurine metabolism in Crohn’s disease: Correlation with efficacy and toxicity. Gut 1996; 39: 401-406.