Dihydropyrimidine dehydrogenase (NADP+)

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dihydropyrimidine dehydrogenase (NADP+)
1gte.jpg
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
DPYD
Protein DPYD PDB 1gt8.png
Identifiers
AliasesDPYD, DHP, DHPDHASE, DPD, dihydropyrimidine dehydrogenase, DYPD
External IDsOMIM: 612779 MGI: 2139667 HomoloGene: 85 GeneCards: DPYD
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000110
NM_001160301

NM_170778

RefSeq (protein)

NP_000101
NP_001153773

NP_740748

Location (UCSC)Chr 1: 97.08 – 98 MbChr 3: 118.36 – 119.23 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

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.[5][6] It is the initial and rate-limiting step in pyrimidine catabolism.[citation needed] It catalyzes the reduction of uracil and thymine.[7] It is also involved in the degradation of the chemotherapeutic drugs 5-fluorouracil and tegafur.[8] It also participates in beta-alanine metabolism and pantothenate and coa biosynthesis.

Terminology[edit]

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[edit]

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[edit]

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.[6]

Interactive pathway map[edit]

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

[[File:
FluoropyrimidineActivity_WP1601go to articlego to articlego to articlego to pathway articlego to pathway articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to PubChem Compoundgo to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to pathway articlego to pathway articlego to articlego to articlego to articlego to articlego to articlego to WikiPathwaysgo to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to article
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FluoropyrimidineActivity_WP1601go to articlego to articlego to articlego to pathway articlego to pathway articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to PubChem Compoundgo to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to pathway articlego to pathway articlego to articlego to articlego to articlego to articlego to articlego to WikiPathwaysgo to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to article
|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[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000188641 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000033308 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ a b "Entrez Gene: DPYD dihydropyrimidine dehydrogenase".
  7. ^ 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.
  8. ^ 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[edit]