Category Archives: Thiopurine methyltransferase enzyme - Part 2

The effects of AZA/6-MP are mediated via the drug’s intracellular conversion to thiopurine nucleotide metabolites, which are incorporated into cellular nucleic acids, a process which leads to inhibition of de novo purine synthesis. As shown in Figure 1, AZA is rapidly converted to 6-MP via nonenzymatic processes, after which 6-MP may be catabo-lized to the inactive metabolite, 6-methylmercaptopurine (6-MMP), or anabolized to the active metabolites, 6-thioguanine nucleotides (6-TG) and 6-MMP ribonucleotides, via competing pathways. The methylation of 6-MP to 6-MMP ribonucleotides is catalyzed by thiopurine methyltransferase (TPMT). Continue reading →

Azathioprine (AZA) and 6-mercaptopurine (6-MP) are purine analogues that interfere with nucleic acid metabolism and cell proliferation, and both drugs have immunosuppressive properties. Both have been shown to be effective for the induction and maintenance of remission in cases of corticosteroid-dependent or corticosteroid-resistant inflammatory bowel disease (IBD) and in the management of fistulizing Crohn’s disease (CD). A meta-analysis has shown that 56% of patients with active CD treated with AZA/6-MP experienced either improvement in their disease state or induction of remission. Continue reading →