Dihydropyrimidine dehydrogenase (NADP+)

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

dihydropyrimidine dehydrogenase (NADP+)
Dihydroprymidine dehydrogenase dimer, Sus scrofa
Identifiers
EC no.1.3.1.2
CAS no.9029-01-0
Alt. namesDihydrothymine dehydrogenase
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins
5,6-dihydrouracil + NADP+ 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

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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

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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

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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

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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

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References

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  1. ^ Takai S, Fernandez-Salguero P, Kimura S, Gonzalez FJ, Yamada K (December 1994). "Assignment of the human dihydropyrimidine dehydrogenase gene (DPYD) to chromosome region 1p22 by fluorescence in situ hybridization". Genomics. 24 (3): 613–4. doi:10.1006/geno.1994.1680. PMID 7713523.
  2. ^ a b "Entrez Gene: DPYD dihydropyrimidine dehydrogenase".
  3. ^ Chung T, Na J, Kim YI, Chang DY, Kim YI, Kim H, Moon HE, Kang KW, Lee DS, Chung JK, Kim SS, Suh-Kim H, Paek SH, Youn H (2016). "Dihydropyrimidine Dehydrogenase Is a Prognostic Marker for Mesenchymal Stem Cell-Mediated Cytosine Deaminase Gene and 5-Fluorocytosine Prodrug Therapy for the Treatment of Recurrent Gliomas". Theranostics. 6 (10): 1477–90. doi:10.7150/thno.14158. PMC 4955049. PMID 27446484.
  4. ^ Caudle KE, Thorn CF, Klein TE, Swen JJ, McLeod HL, Diasio RB, Schwab M (December 2013). "Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing". Clinical Pharmacology and Therapeutics. 94 (6): 640–5. doi:10.1038/clpt.2013.172. PMC 3831181. PMID 23988873.

Further reading

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