Dihydropyrimidine Dehydrogenase (DPYD)

Dihydropyrimidine dehydrogenase (DPD) is an enzyme that is involved in pyrimidine degradation. It is the initial and rate-limiting step in pyrimidine catabolism. It catalyzes the reduction of uracil and thymine. It is also involved in the degradation of the chemotherapeutic drugs 5-fluorouracil and Tegafur-uracil.The sequence of the gene suggested that DPD has at least 3 distinct domains: a possible NADPH binding site and FAD-binding site in the N terminus, 2 motifs of putative iron/sulfur-binding sites near the C terminus, and a peptide domain corresponding to the uracil-binding site.Expression of the pig enzyme in E. coli catalyzed the reduction of uracil, thymine, and 5-fluorouracil (5FU) with kinetics approximating those published for the enzyme purified from mammalian liver.