Dihydropyrimidine dehydrogenase (NADP+)
Template:Cs1 config Template:Short description Template:Infobox enzyme
In enzymology, a dihydropyrimidine dehydrogenase (NADP+) (Template:EC number) 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.[1][2] It is the initial and rate-limiting step in pyrimidine catabolism.Template: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 Template:PDB link, Template:PDB link, Template:PDB link, Template:PDB link, and Template:PDB link.
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
Template:FluoropyrimidineActivity WP1601
See also
- Dihydropyrimidine dehydrogenase deficiency, a genetic disorder
- Cancer pharmacogenomics
References
Further reading
- Template:Cite journal
- Template:Cite journal
- Template:Cite journal
- Template:Cite journal
- Template:Cite journal
- Template:Cite journal
- Template:Cite journal
- Template:Cite journal
- Template:Cite journal
- Template:Cite journal
- Template:Cite journal
- Template:Cite journal
- Template:Cite journal
- Template:Cite journal
- Template:Cite journal
- Template:Cite journal
- Template:Cite journal
- Template:Cite journal
- Template:Cite journal
- Template:Cite journal
Template:PDB Gallery Template:CH-CH oxidoreductases Template:Enzymes Template:Nucleotide metabolism Template:Portal bar
- ↑ Template:Cite journal
- ↑ 2.0 2.1 Template:Cite web
- ↑ Cite error: Invalid
<ref>tag; no text was provided for refs namedChung - ↑ Cite error: Invalid
<ref>tag; no text was provided for refs namedCaudle