Dihydropyrimidine dehydrogenase (NADP+)

dihydropyrimidine dehydrogenase (NADP+)
Dihydroprymidine dehydrogenase dimer, Sus scrofa
Identifiers
EC no.	1.3.1.2
CAS no.	9029-01-0
Alt. names	Dihydrothymine dehydrogenase
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

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

5,6-dihydrouracil + NADP⁺ ${\displaystyle \rightleftharpoons }$ 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.^[1][2] It is the initial and rate-limiting step in pyrimidine catabolism.^{[citation needed]} It catalyzes the reduction of uracil and thymine.^[3] It is also involved in the degradation of the chemotherapeutic drugs 5-fluorouracil and tegafur.^[4] 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.^[2]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.^{[§ 1]}

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|alt=Fluorouracil (5-FU) Activity edit]]

Fluorouracil (5-FU) Activity edit

1. ^ The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601".

See also

• Dihydropyrimidine dehydrogenase deficiency, a genetic disorder
• Cancer pharmacogenomics

References

Further reading