page_title: Thymidine phosphorylase
section_title: Mechanism
hierarchical_section_title: Thymidine phosphorylase / Mechanism
caption_attribution_description: English: Thymidine phosphorylase mechanism
context_page_description: Thymidine phosphorylase is an enzyme that is encoded by the TYMP gene and catalyzes the reaction:
  thymidine + phosphate thymine + 2-deoxy-alpha-D-ribose 1-phosphate
  Thymidine phosphorylase is involved in purine metabolism, pyrimidine metabolism, and other metabolic pathways. Variations in thymidine phosphorylase and the TYMP gene that encode it are associated with mitochondrial neurogastrointestinal encephalopathy syndrome and bladder cancer.
context_section_description: Thymidine phosphorylase catalyzes the reversible phosphorylation of thymidine, deoxyuridine, and their analogs (except deoxycytidine) to their respective bases (thymine/uracil) and 2-deoxyribose 1-phosphate. The enzyme follows a sequential mechanism, where phosphate binds before thymidine (or deoxyuridine, etc.) and 2-deoxyribose 1-phosphate leaves after the nitrogenous base. The thymidine is bound in a high-energy conformation, in which the glycosidic bond weakens as the phosphate attacks the C1 position of the ribose ring, as shown below. The enzyme can then transfer deoxyribose 1-phosphate to other nitrogenous bases. 
  Further experiments have shown that thymine inhibits the enzyme via both substrate inhibition and nonlinear product inhibition. This suggests that thymine can inhibit the enzyme via multiple sites. The enzyme also displays cooperativity with respect to both thymidine and phosphate in the presence of thymine, which suggests that thymidine phosphorylase has several allosteric and/or catalytic sites as well.
caption: Thymidine phosphorylase mechanism
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