Figure 1
Figure 1. Thiopurine conversion to active nucleotides and methylated compounds. MP is converted to thioguanine nucleotides (TGNs) via 3 enzymatic steps and TG via 1 step. Both MP and TG undergo S-methylation by thiopurine methyltransferase (TPMT) to methyl-mercaptopurine (meMP) and methyl-thioguanine (meTG), respectively. TPMT competes with hypoxanthine-guanine phosphoribosyltransferase (HGPRT), the first enzymatic step in conversion of thiopurines to TGNs. Thioinosine monophosphate (TIMP), thioxanthene monophosphate (TXMP), and thioguanylate (TGMP) are also S-methylated by TPMT. Methyl-6-thioinosine monophosphate (meTIMP), a product of MP but not TG metabolism, is a potent inhibitor of de novo purine synthesis. meTXMP indicates methyl-thioxanthene monophosphate; IMP, inosine monophosphate; and meTGMP, methyl-thioguanylate.

Thiopurine conversion to active nucleotides and methylated compounds. MP is converted to thioguanine nucleotides (TGNs) via 3 enzymatic steps and TG via 1 step. Both MP and TG undergo S-methylation by thiopurine methyltransferase (TPMT) to methyl-mercaptopurine (meMP) and methyl-thioguanine (meTG), respectively. TPMT competes with hypoxanthine-guanine phosphoribosyltransferase (HGPRT), the first enzymatic step in conversion of thiopurines to TGNs. Thioinosine monophosphate (TIMP), thioxanthene monophosphate (TXMP), and thioguanylate (TGMP) are also S-methylated by TPMT. Methyl-6-thioinosine monophosphate (meTIMP), a product of MP but not TG metabolism, is a potent inhibitor of de novo purine synthesis. meTXMP indicates methyl-thioxanthene monophosphate; IMP, inosine monophosphate; and meTGMP, methyl-thioguanylate.

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