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Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases |
Basic Information |
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Enzyme Number | 1.3.1.2 |
Official Name | dihydropyrimidine dehydrogenase (NADP+) |
Name from literature | dihydropyrimidine dehydrogenase |
Pathway from literature | 5-fluorouracil (5-FU) chemotherapy catabolic pathway |
Pathway from KEGG |
Metabolism of Other Amino Acids; beta-Alanine metabolism; map00410 |
Xenobiotics Biodegradation and Metabolism; Drug metabolism - other enzymes; map00983 | |
Nucleotide Metabolism; Pyrimidine metabolism; map00240 | |
Organisms | Human (9606) |
Genome localization | 1p22[1806 ], |
Comments | Also acts on dihydrothymine. |
Rate-limiting Description | "In humans, 80-90% of an administered dose of 5-fluorouracil (5-FU) is degraded by dihydropyrimidine dehydrogenase (DPD; EC 1.3.1.2), the initial rate-limiting enzyme in pyrimidine catabolism." (10473079) |
| "An alternate approach involves the inhibition of gastrointestinal degradation via coadministration of an inhibitor of dihydropyrimidine dehydrogenase, the rate-limiting enzyme in 5-FU catabolism." (10887632) |
| "Thymidine phosphorylase (dThdPase) is the rate-limiting enzyme that metabolizes 5'-deoxy-5-fluorouridine (5'-dFUrd, doxifluridine), an intermediate metabolite of capecitabine, to the active drug 5-fluorouracil (5-FUra), while dihydropyrimidine dehydrogenase (DPD) catabolizes 5-FUra to an inactive molecule." (10853015) |
Regulatory Information |
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Upstream transcription factor | |
Regulatory type | Detail |
key enzyme; | "Dihydropyrimidine dehydrogenase (DPD) is a key enzyme in the metabolic catabolism of chemotherapeutic agent 5-fluorouracil (5FU) and its derivatives, including capecitabine." (17350823) |
transcriptional factor;"Sp1(6667),Sp3(6670)" | "Sp1 is a strong activator, while Sp3 by its own is a weak activator of the DPYD promoter." (16806531) |
transcriptional factor;Sp1(6667) | "active transcription machinery for DPYD is present in RKO colorectal cancer cells, but promoter binding of Sp1, a transactivator of DPYD, was inhibited, which on subsequent examination was shown to be associated with dense promoter methylation" (17612628) |
phosphorylation; | Q12882 |
phosphorylation; | Q12882:from_uniprot:577_Phosphoserine |
Gene ontology |
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Gene ontology |
GO:0050661 (F) NADP binding [Q12882 ]; |
Tissue expression |
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Tissue From HPRD |
Leukocyte [02036 ]; |
Tissue specificity |
Found in most tissues with greatest activity found in liver and peripheral blood mononuclear cells [Q12882 ]; |
Subcellular localization |
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Localization |
cytoplasm [Q12882 ]; |
Disease relevance |
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Disease |
Defects in DPYD are the cause of dihydropyrimidine dehydrogenase deficiency (DPYD deficiency) [MIM:274270]; |
Links |
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SwissProt | |
Entrez Gene | |
HPRD |
Copyright 2009, Center for Bioinformatics | |||
Last Modified: 2009-03-24 | |||
Design by Zhao Min |