Dihydropyrimidine dehydrogenase (NADP+)

In enzymology, a dihydropyrimidine dehydrogenase (NADP+) (EC 1.3.1.2) is an enzyme that catalyzes the chemical reaction

5,6-dihydrouracil + NADP⁺ $\rightleftharpoons$ uracil + NADPH + H⁺

Thus, the two substrates of this enzyme are 5,6-dihydrouracil and NADP⁺, whereas its 3 products are uracil, NADPH, and H⁺.

In humans the enzyme is encoded by the DPYD gene. 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. It also 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 (NADP+)
• 4,5-dihydrothymine: oxidoreductase
• DPD
• DHPDH
• dehydrogenase, dihydrouracil (nicotinamide adenine dinucleotide, phosphate)
• DHU dehydrogenase
• hydropyrimidine dehydrogenase
• dihydropyrimidine dehydrogenase (NADP+)

Structural studies

As of late 2007, 5 structures have been solved for this class of enzymes, with PDB accession codes 1GT8, 1GTE, 1GTH, 1H7W, and 1H7X.

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.

See also

• Dihydropyrimidine dehydrogenase deficiency, a genetic disorder
• Cancer pharmacogenomics

Further reading

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