Purine metabolism via formation of thioguanine nucleotides

Purine metabolism via formation of thioguanine nucleotides describes the metabolic activation of thiopurine drugs like azathioprine and 6-mercaptopurine into active metabolites (StatPearls, 2023). This pathway primarily involves the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT), which converts these prodrugs into 6-thioguanine nucleotides (6-TGNs) (PharmGKB, 2021). Once formed, 6-TGNs are incorporated into the DNA and RNA of proliferating cells, leading to the inhibition of purine synthesis and the induction of apoptosis (National Library of Medicine, 2022). This mechanism is central to the therapeutic efficacy of thiopurines in treating acute lymphoblastic leukemia and inflammatory bowel diseases (PubMed, 2020). However, the pathway is highly sensitive to genetic polymorphisms in enzymes like thiopurine S-methyltransferase (TPMT) and NUDT15, which can lead to toxic accumulations of metabolites (NIH, 2022).

Other names

Thiopurine metabolismPurine salvage pathway activation6-thioguanine nucleotide formation

Thiopurine prodrugs are metabolized by enzymes such as HGPRT into active thioguanine nucleotides (TGNs), which incorporate into DNA and RNA to inhibit cell proliferation and induce immunosuppression.