Dihydropyrimidine Dehydrogenase (DPD)

Dihydropyrimidine Dehydrogenase (DPD) is a pyrimidine catabolic enzyme that catalyzes the two-electron reduction of pyrimidine bases uracil and thymine. Dihydropyrimidine dehydrogenase catalyzes the first step of pyrimidine catabolism by promoting the reduction of the 5,6-vinylic bond of thymine or uracil with electrons acquired from NADPH. Mammalian Dihydropyrimidine dehydrogenase is a functional homodimer and each subunit contains an FAD, an FMN and four Fe4S4 centers with two Fe4S4 centers from each subunit forming an electron transfer conduit that link the flavins within each subunit. Dihydropyrimidine dehydrogenase accepts the pervasive chemotherapeutic 5-Fluorouracil as a substrate, severely shortening its pharmacological half-life and dictating the use of elaborate compensatory administration protocols to achieve efficacious toxicity^[1].