Pharmacogenetics in inflammatory bowel disease

Figure 1 Simplified scheme of AZA metabolism: AZA is non-enzymatically converted to 6-MP. 6-MP is converted into the 6-thioinosine monophosphate (6-TIMP) by the enzyme hypoxanthine guanine phosphoribosyl-transferase (HGPRT). 6-TIMP is further metabolized to thioguanine mono, di and triphosphates [6-thioguanine nucleotides (TGN)]. Alternatively 6-MP can be inactivated by xanthine oxidase (XO) into 6-thiouric acid (6-TU) or by TPMT into 6-methylmercaptopurine (6-MMP). TPMT also catalyses the methylation of the nucleotide metabolites including 6-TIMP and 6-thioguanosine-5’-monophosphate to 6-methylmercaptopurine (6-MMPR). Inosine monophosphate dehydrogenase (IMPDH) and guanine monophosphate synthetase (GMPS). Inosine triphosphate pyrophosphatase (ITPA), 6-thioinosine triphosphate pyrophosphate (6-TITP).