Dihydropyrimidine dehydrogenase: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Bot: Automated text replacement (-{{SIB}} + & -{{EH}} + & -{{EJ}} + & -{{Editor Help}} + & -{{Editor Join}} +))
 
imported>Boghog
(removing redundant protein infobox)
 
(One intermediate revision by one other user not shown)
Line 1: Line 1:
{{protein
{{Infobox enzyme
|name=dihydropyrimidine dehydrogenase
| name = Dihydropyrimidine dehydrogenase (NADP(+))
|caption=
| AltNames =Dihydrothymine dehydrogenase
|image=
| image =
|width=
| image_size =
|HGNCid=3012
| caption =
|Symbol=DPYD
| EC_number = 1.3.1.2
|AltSymbols=
| CAS_number = 9029-01-0
|EntrezGene=1806
| GO_code = 0017113
|OMIM=274270
|RefSeq=NM_000110
|UniProt=
|PDB=
|ECnumber=1.3.1.2
|Chromosome=1
|Arm=p
|Band=22
|LocusSupplementaryData=
}}
}}
{{#invoke:Infobox_gene|getTemplateData|QID=Q18022858}}
'''Dihydropyrimidine dehydrogenase''' ('''DPD''') is an [[enzyme]] that is involved in [[pyrimidine]] degradation that in humans is encoded by the ''DPYD'' [[gene]].<ref name="pmid7713523">{{cite journal | vauthors = Takai S, Fernandez-Salguero P, Kimura S, Gonzalez FJ, Yamada K | title = Assignment of the human dihydropyrimidine dehydrogenase gene (DPYD) to chromosome region 1p22 by fluorescence in situ hybridization | journal = Genomics | volume = 24 | issue = 3 | pages = 613–4 | date = December 1994 | pmid = 7713523 | pmc =  | doi = 10.1006/geno.1994.1680 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: DPYD dihydropyrimidine dehydrogenase| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1806| accessdate = }}</ref> It is the initial and rate-limiting step in pyrimidine catabolism.{{fact|date=April 2017}} It catalyzes the reduction of [[uracil]] and [[thymine]].<ref name="Chung" /> It is also involved in the degradation of the chemotherapeutic drugs [[5-fluorouracil]] and [[tegafur]].<ref name="Caudle" />


==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.<ref name="entrez" />


==Overview==
== Interactive pathway map ==
'''Dihydropyrimidine dehydrogenase''' ('''DPD''') is an [[enzyme]] that is involved in [[pyrimidine]] degradation. 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 drug [[5-fluorouracil]].
{{FluoropyrimidineActivity WP1601|highlight=DPYD}}


==See also==
== See also ==
* [[Dihydropyrimidine dehydrogenase deficiency]]
* [[Dihydropyrimidine dehydrogenase deficiency]], a genetic disorder


==External links==
== References ==
* [http://www.mdl-labs.com  dpd genotype testing (www.mdl-labs.com)]
{{reflist|refs=
<ref name="Chung">{{cite journal | vauthors = 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 | title = 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 | journal = Theranostics | volume = 6 | issue = 10 | pages = 1477–90 | year = 2016 | pmid = 27446484 | pmc = 4955049 | doi = 10.7150/thno.14158 }}</ref>


<ref name="Caudle">{{cite journal | vauthors = Caudle KE, Thorn CF, Klein TE, Swen JJ, McLeod HL, Diasio RB, Schwab M | title = Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing | journal = Clinical Pharmacology and Therapeutics | volume = 94 | issue = 6 | pages = 640–5 | date = December 2013 | pmid = 23988873 | pmc = 3831181 | doi = 10.1038/clpt.2013.172 }}</ref>
}}
== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Hoff PM, Royce M, Medgyesy D, Brito R, Pazdur R | title = Oral fluoropoyrimidines | journal = Seminars in Oncology | volume = 26 | issue = 6 | pages = 640–6 | date = December 1999 | pmid = 10606257 | doi =  }}
* {{cite journal | vauthors = Schneider HB, Becker H | title = Impact of dihydropyrimidine dehydrogenase on 5-fluorouracil treatment in cancer patients | journal = European Journal of Medical Research | volume = 8 | issue = 5 | pages = 226–8 | date = May 2003 | pmid = 12844478 | doi =  }}
* {{cite journal | vauthors = Omura K | title = Clinical implications of dihydropyrimidine dehydrogenase (DPD) activity in 5-FU-based chemotherapy: mutations in the DPD gene, and DPD inhibitory fluoropyrimidines | journal = International Journal of Clinical Oncology | volume = 8 | issue = 3 | pages = 132–8 | date = June 2003 | pmid = 12851836 | doi = 10.1007/s10147-003-0330-z }}
* {{cite journal | vauthors = Lee W, Lockhart AC, Kim RB, Rothenberg ML | title = Cancer pharmacogenomics: powerful tools in cancer chemotherapy and drug development | journal = The Oncologist | volume = 10 | issue = 2 | pages = 104–11 | date = February 2005 | pmid = 15709212 | doi = 10.1634/theoncologist.10-2-104 }}
* {{cite journal | vauthors = Lu ZH, Zhang R, Diasio RB | title = Purification and characterization of dihydropyrimidine dehydrogenase from human liver | journal = The Journal of Biological Chemistry | volume = 267 | issue = 24 | pages = 17102–9 | date = August 1992 | pmid = 1512248 | doi =  }}
* {{cite journal | vauthors = Porter DJ, Chestnut WG, Merrill BM, Spector T | title = Mechanism-based inactivation of dihydropyrimidine dehydrogenase by 5-ethynyluracil | journal = The Journal of Biological Chemistry | volume = 267 | issue = 8 | pages = 5236–42 | date = March 1992 | pmid = 1544906 | doi =  }}
* {{cite journal | vauthors = Dupuis A, Skehel JM, Walker JE | title = A homologue of a nuclear-coded iron-sulfur protein subunit of bovine mitochondrial complex I is encoded in chloroplast genomes | journal = Biochemistry | volume = 30 | issue = 11 | pages = 2954–60 | date = March 1991 | pmid = 1901022 | doi = 10.1021/bi00225a032 }}
* {{cite journal | vauthors = Eggink G, Engel H, Vriend G, Terpstra P, Witholt B | title = Rubredoxin reductase of Pseudomonas oleovorans. Structural relationship to other flavoprotein oxidoreductases based on one NAD and two FAD fingerprints | journal = Journal of Molecular Biology | volume = 212 | issue = 1 | pages = 135–42 | date = March 1990 | pmid = 2319593 | doi = 10.1016/0022-2836(90)90310-I }}
* {{cite journal | vauthors = Tuchman M, Roemeling RV, Hrushesky WA, Sothern RB, O'Dea RF | title = Dihydropyrimidine dehydrogenase activity in human blood mononuclear cells | journal = Enzyme | volume = 42 | issue = 1 | pages = 15–24 | year = 1989 | pmid = 2528450 | doi =  }}
* {{cite journal | vauthors = Diasio RB, Beavers TL, Carpenter JT | title = Familial deficiency of dihydropyrimidine dehydrogenase. Biochemical basis for familial pyrimidinemia and severe 5-fluorouracil-induced toxicity | journal = The Journal of Clinical Investigation | volume = 81 | issue = 1 | pages = 47–51 | date = January 1988 | pmid = 3335642 | pmc = 442471 | doi = 10.1172/JCI113308 }}
* {{cite journal | vauthors = Yokota H, Fernandez-Salguero P, Furuya H, Lin K, McBride OW, Podschun B, Schnackerz KD, Gonzalez FJ | title = cDNA cloning and chromosome mapping of human dihydropyrimidine dehydrogenase, an enzyme associated with 5-fluorouracil toxicity and congenital thymine uraciluria | journal = The Journal of Biological Chemistry | volume = 269 | issue = 37 | pages = 23192–6 | date = September 1994 | pmid = 8083224 | doi =  }}
* {{cite journal | vauthors = Lu Z, Zhang R, Diasio RB | title = Dihydropyrimidine dehydrogenase activity in human peripheral blood mononuclear cells and liver: population characteristics, newly identified deficient patients, and clinical implication in 5-fluorouracil chemotherapy | journal = Cancer Research | volume = 53 | issue = 22 | pages = 5433–8 | date = November 1993 | pmid = 8221682 | doi =  }}
* {{cite journal | vauthors = Vreken P, Van Kuilenburg AB, Meinsma R, Smit GP, Bakker HD, De Abreu RA, van Gennip AH | title = A point mutation in an invariant splice donor site leads to exon skipping in two unrelated Dutch patients with dihydropyrimidine dehydrogenase deficiency | journal = Journal of Inherited Metabolic Disease | volume = 19 | issue = 5 | pages = 645–54 | year = 1997 | pmid = 8892022 | doi = 10.1007/BF01799841 }}
* {{cite journal | vauthors = Johnson MR, Wang K, Tillmanns S, Albin N, Diasio RB | title = Structural organization of the human dihydropyrimidine dehydrogenase gene | journal = Cancer Research | volume = 57 | issue = 9 | pages = 1660–3 | date = May 1997 | pmid = 9135003 | doi =  }}
* {{cite journal | vauthors = Fernandez-Salguero PM, Sapone A, Wei X, Holt JR, Jones S, Idle JR, Gonzalez FJ | title = Lack of correlation between phenotype and genotype for the polymorphically expressed dihydropyrimidine dehydrogenase in a family of Pakistani origin | journal = Pharmacogenetics | volume = 7 | issue = 2 | pages = 161–3 | date = April 1997 | pmid = 9170156 | doi = 10.1097/00008571-199704000-00012 }}
* {{cite journal | vauthors = Vreken P, Van Kuilenburg AB, Meinsma R, van Gennip AH | title = Identification of novel point mutations in the dihydropyrimidine dehydrogenase gene | journal = Journal of Inherited Metabolic Disease | volume = 20 | issue = 3 | pages = 335–8 | date = July 1997 | pmid = 9266349 | doi = 10.1023/A:1005357307122 }}
* {{cite journal | vauthors = Vreken P, Van Kuilenburg AB, Meinsma R, van Gennip AH | title = Dihydropyrimidine dehydrogenase (DPD) deficiency: identification and expression of missense mutations C29R, R886H and R235W | journal = Human Genetics | volume = 101 | issue = 3 | pages = 333–8 | date = December 1997 | pmid = 9439663 | doi = 10.1007/s004390050637 }}
* {{cite journal | vauthors = Ogura K, Nishiyama T, Takubo H, Kato A, Okuda H, Arakawa K, Fukushima M, Nagayama S, Kawaguchi Y, Watabe T | title = Suicidal inactivation of human dihydropyrimidine dehydrogenase by (E)-5-(2-bromovinyl)uracil derived from the antiviral, sorivudine | journal = Cancer Letters | volume = 122 | issue = 1-2 | pages = 107–13 | date = January 1998 | pmid = 9464498 | doi = 10.1016/S0304-3835(97)00377-7 }}
{{refend}}
{{PDB Gallery|geneid=1806}}


{{Nucleotide metabolism}}
{{Nucleotide metabolism}}
{{WH}}
 
{{WS}}
[[Category:EC 1.3.1]]
 
{{enzyme-stub}}

Latest revision as of 10:51, 7 October 2018

Dihydropyrimidine dehydrogenase (NADP(+))
Identifiers
EC number1.3.1.2
CAS number9029-01-0
Alt. namesDihydrothymine dehydrogenase
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Dihydropyrimidine dehydrogenase (DPD) is an enzyme that is involved in pyrimidine degradation that in humans 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]

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]

[[File:
<imagemap> Image:FluoropyrimidineActivity_WP1601.png
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
[[
]]
<imagemap> Image:FluoropyrimidineActivity_WP1601.png
|{{{bSize}}}px|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

References

  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. ↑ 2.0 2.1 "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

  • Hoff PM, Royce M, Medgyesy D, Brito R, Pazdur R (December 1999). "Oral fluoropoyrimidines". Seminars in Oncology. 26 (6): 640–6. PMID 10606257.
  • Schneider HB, Becker H (May 2003). "Impact of dihydropyrimidine dehydrogenase on 5-fluorouracil treatment in cancer patients". European Journal of Medical Research. 8 (5): 226–8. PMID 12844478.
  • Omura K (June 2003). "Clinical implications of dihydropyrimidine dehydrogenase (DPD) activity in 5-FU-based chemotherapy: mutations in the DPD gene, and DPD inhibitory fluoropyrimidines". International Journal of Clinical Oncology. 8 (3): 132–8. doi:10.1007/s10147-003-0330-z. PMID 12851836.
  • Lee W, Lockhart AC, Kim RB, Rothenberg ML (February 2005). "Cancer pharmacogenomics: powerful tools in cancer chemotherapy and drug development". The Oncologist. 10 (2): 104–11. doi:10.1634/theoncologist.10-2-104. PMID 15709212.
  • Lu ZH, Zhang R, Diasio RB (August 1992). "Purification and characterization of dihydropyrimidine dehydrogenase from human liver". The Journal of Biological Chemistry. 267 (24): 17102–9. PMID 1512248.
  • Porter DJ, Chestnut WG, Merrill BM, Spector T (March 1992). "Mechanism-based inactivation of dihydropyrimidine dehydrogenase by 5-ethynyluracil". The Journal of Biological Chemistry. 267 (8): 5236–42. PMID 1544906.
  • Dupuis A, Skehel JM, Walker JE (March 1991). "A homologue of a nuclear-coded iron-sulfur protein subunit of bovine mitochondrial complex I is encoded in chloroplast genomes". Biochemistry. 30 (11): 2954–60. doi:10.1021/bi00225a032. PMID 1901022.
  • Eggink G, Engel H, Vriend G, Terpstra P, Witholt B (March 1990). "Rubredoxin reductase of Pseudomonas oleovorans. Structural relationship to other flavoprotein oxidoreductases based on one NAD and two FAD fingerprints". Journal of Molecular Biology. 212 (1): 135–42. doi:10.1016/0022-2836(90)90310-I. PMID 2319593.
  • Tuchman M, Roemeling RV, Hrushesky WA, Sothern RB, O'Dea RF (1989). "Dihydropyrimidine dehydrogenase activity in human blood mononuclear cells". Enzyme. 42 (1): 15–24. PMID 2528450.
  • Diasio RB, Beavers TL, Carpenter JT (January 1988). "Familial deficiency of dihydropyrimidine dehydrogenase. Biochemical basis for familial pyrimidinemia and severe 5-fluorouracil-induced toxicity". The Journal of Clinical Investigation. 81 (1): 47–51. doi:10.1172/JCI113308. PMC 442471. PMID 3335642.
  • Yokota H, Fernandez-Salguero P, Furuya H, Lin K, McBride OW, Podschun B, Schnackerz KD, Gonzalez FJ (September 1994). "cDNA cloning and chromosome mapping of human dihydropyrimidine dehydrogenase, an enzyme associated with 5-fluorouracil toxicity and congenital thymine uraciluria". The Journal of Biological Chemistry. 269 (37): 23192–6. PMID 8083224.
  • Lu Z, Zhang R, Diasio RB (November 1993). "Dihydropyrimidine dehydrogenase activity in human peripheral blood mononuclear cells and liver: population characteristics, newly identified deficient patients, and clinical implication in 5-fluorouracil chemotherapy". Cancer Research. 53 (22): 5433–8. PMID 8221682.
  • Vreken P, Van Kuilenburg AB, Meinsma R, Smit GP, Bakker HD, De Abreu RA, van Gennip AH (1997). "A point mutation in an invariant splice donor site leads to exon skipping in two unrelated Dutch patients with dihydropyrimidine dehydrogenase deficiency". Journal of Inherited Metabolic Disease. 19 (5): 645–54. doi:10.1007/BF01799841. PMID 8892022.
  • Johnson MR, Wang K, Tillmanns S, Albin N, Diasio RB (May 1997). "Structural organization of the human dihydropyrimidine dehydrogenase gene". Cancer Research. 57 (9): 1660–3. PMID 9135003.
  • Fernandez-Salguero PM, Sapone A, Wei X, Holt JR, Jones S, Idle JR, Gonzalez FJ (April 1997). "Lack of correlation between phenotype and genotype for the polymorphically expressed dihydropyrimidine dehydrogenase in a family of Pakistani origin". Pharmacogenetics. 7 (2): 161–3. doi:10.1097/00008571-199704000-00012. PMID 9170156.
  • Vreken P, Van Kuilenburg AB, Meinsma R, van Gennip AH (July 1997). "Identification of novel point mutations in the dihydropyrimidine dehydrogenase gene". Journal of Inherited Metabolic Disease. 20 (3): 335–8. doi:10.1023/A:1005357307122. PMID 9266349.
  • Vreken P, Van Kuilenburg AB, Meinsma R, van Gennip AH (December 1997). "Dihydropyrimidine dehydrogenase (DPD) deficiency: identification and expression of missense mutations C29R, R886H and R235W". Human Genetics. 101 (3): 333–8. doi:10.1007/s004390050637. PMID 9439663.
  • Ogura K, Nishiyama T, Takubo H, Kato A, Okuda H, Arakawa K, Fukushima M, Nagayama S, Kawaguchi Y, Watabe T (January 1998). "Suicidal inactivation of human dihydropyrimidine dehydrogenase by (E)-5-(2-bromovinyl)uracil derived from the antiviral, sorivudine". Cancer Letters. 122 (1–2): 107–13. doi:10.1016/S0304-3835(97)00377-7. PMID 9464498.
Retrieved from "https://www.wikidoc.org/index.php?title=Dihydropyrimidine_dehydrogenase&oldid=1530364"