Figure 2.

Principal thiopurine metabolic pathways. Azathioprine (AZA) is rapidly converted to 6-mercaptopurine (6-MP) by a non-enzymatic process. 6-MP is subsequently metabolized to immunologically inactive 6-methylmercaptopurine metabolite ribonucleotides (6-MMP) by thiopurine methyltransferase (TPMT). Th e alternative competing pathway is conversion to 6-thioinosine 5-monophosphate (6-TImP) by intracellular hypoxanthineguanine phosphoribosyltransferase (HPRT) and then further enzymatic transformation by 2 separate metabolic pathways to produce either 6-thianoguanine metabolites (6-TGN) through an enzymatic cascade including inosine monophosphate dehydrogenase (IMPDH) and guanosine monophosphate synthase (GMPS) or, alternatively, by TPMT to 6-MMP