Dihydropyrimidine dehydrogenase (NADP+)

In enzymology, dihydropyrimidine dehydrogenase is an enzyme that catalyzes the chemical reaction
In the catabolism of uracil, the enzyme converts uracil to dihydrouracil using nicotinamide adenine dinucleotide phosphate as its cofactor. It can also act on thymine to give dihydrothymine.
In humans the enzyme is encoded by the DPYD gene. It is the initial and rate-limiting step in pyrimidine catabolism. It is also involved in the degradation of the chemotherapeutic drugs 5-fluorouracil and tegafur. It participates in beta-alanine metabolism and pantothenate and coa biosynthesis.

Terminology

The systematic name of this enzyme class is 5,6-dihydrouracil:NADP+ 5-oxidoreductase.
Other names in common use include:dihydrothymine dehydrogenase

dihydrouracil dehydrogenase
4,5-dihydrothymine: oxidoreductase
DPD
DHPDH
dehydrogenase, dihydrouracil
DHU dehydrogenase
hydropyrimidine dehydrogenase
'''dihydropyrimidine dehydrogenase '''

Structural studies

As of late 2007, 5 structures have been solved for this class of enzymes, with PDB accession codes,,,, and.

Function

The protein is a pyrimidine catabolic enzyme and the initial and rate-limiting factor in the pathway of uracil and thymidine catabolism. Genetic deficiency of this enzyme results in an error in pyrimidine metabolism associated with thymine-uraciluria and an increased risk of toxicity in cancer patients receiving 5-fluorouracil chemotherapy.