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5,6-dihydrouracil + NAD+
uracil + NADH + H+
5-fluorouracil + NAD+
? + NADH
5-fluorouracil + NAD+
alpha-fluoro-beta-alanine + NADH + H+
-
-
-
-
?
5-fluorouracil + NADH + H+
5-fluoro-5,6-dihydrouracil + NAD+
5-fluorouracil + NADPH + H+
5-fluoro-5,6-dihydrouracil + NADP+
capecitabine + NAD+
?
-
-
-
-
?
dihydrothymine + NAD+
thymine + NADH + H+
-
-
-
?
thymine + NAD(P)H + H+
dihydrothymine + NAD(P)+
-
-
-
r
thymine + NADH + H+
5,6-dihydrothymine + NAD+
thymine + NADH + H+
dihydrothymine + NAD+
-
-
-
r
uracil + NAD(P)H + H+
5,6-dihydrouracil + NAD(P)+
uracil + NADH + H+
5,6-dihydrouracil + NAD+
additional information
?
-
5,6-dihydrouracil + NAD+
uracil + NADH + H+
-
-
-
?
5,6-dihydrouracil + NAD+
uracil + NADH + H+
-
-
-
-
r
5-fluorouracil + NAD+
? + NADH
-
-
-
-
r
5-fluorouracil + NAD+
? + NADH
-
rate-limiting step in the elimination of the chemotherapeutic drug fluoropyrimidine
-
-
r
5-fluorouracil + NADH + H+
5-fluoro-5,6-dihydrouracil + NAD+
-
-
-
-
?
5-fluorouracil + NADH + H+
5-fluoro-5,6-dihydrouracil + NAD+
-
-
-
-
?
5-fluorouracil + NADH + H+
5-fluoro-5,6-dihydrouracil + NAD+
-
-
-
r
5-fluorouracil + NADH + H+
5-fluoro-5,6-dihydrouracil + NAD+
-
-
-
-
?
5-fluorouracil + NADH + H+
5-fluoro-5,6-dihydrouracil + NAD+
-
-
dihydrofluorouracil is further metabolized to 2'-fluoro-beta-alanine
-
?
5-fluorouracil + NADH + H+
5-fluoro-5,6-dihydrouracil + NAD+
-
dihydropyrimidine dehydrogenase is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil
-
-
?
5-fluorouracil + NADH + H+
5-fluoro-5,6-dihydrouracil + NAD+
-
development of a detection method using 2'-fluoro-beta-alanine derivatization with o-phthalaldehyde at room temperature and mass spectrometric analysis by the liquid chromatography-mass spectrometry-electrospray ionization system, method evaluation and optimization, overview
dihydrofluorouracil is further metabolized to 2'-fluoro-beta-alanine
-
?
5-fluorouracil + NADPH + H+
5-fluoro-5,6-dihydrouracil + NADP+
-
-
-
?
5-fluorouracil + NADPH + H+
5-fluoro-5,6-dihydrouracil + NADP+
-
-
-
?
thymine + NADH + H+
5,6-dihydrothymine + NAD+
-
-
-
-
?
thymine + NADH + H+
5,6-dihydrothymine + NAD+
-
-
-
-
?
uracil + NAD(P)H + H+
5,6-dihydrouracil + NAD(P)+
Clostridium uracilicum
-
high specificity for uracil
-
r
uracil + NAD(P)H + H+
5,6-dihydrouracil + NAD(P)+
Clostridium uracilicum
-
reductive pathway of uracil degradation
-
?
uracil + NAD(P)H + H+
5,6-dihydrouracil + NAD(P)+
-
preferred substrate
-
-
?
uracil + NADH + H+
5,6-dihydrouracil + NAD+
-
-
-
-
?
uracil + NADH + H+
5,6-dihydrouracil + NAD+
-
-
-
-
?
uracil + NADH + H+
5,6-dihydrouracil + NAD+
-
-
-
r
uracil + NADH + H+
5,6-dihydrouracil + NAD+
-
-
-
-
?
additional information
?
-
-
the enzyme does not use NADPH as cosubstrate
-
-
?
additional information
?
-
-
the enzyme does not use NADPH as cosubstrate
-
-
?
additional information
?
-
no substrate: orotate
-
-
?
additional information
?
-
no substrate: orotate
-
-
?
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Campbell, L.L.
Reductive Degradation of pyrimidines. III. purification and properties of dihydrouracil dehydrogenase
J. Biol. Chem.
227
693-700
1957
Clostridium uracilicum
brenda
Hallock, R.O.; Yamada, E.W.
Pyrimidine reducing enzymes of rat liver
Can. J. Biochem.
54
178-184
1976
Rattus norvegicus
brenda
Haaz, M.C.; Fischel, J.L.; Formento, P.; Renee, N.; Etienne, M.C.; Milano, G.
Impact of different fluorouracil biochemical modulators on cellular dihydropyrimidine dehydrogenase
Cancer Chemother. Pharmacol.
38
52-58
1996
Homo sapiens
brenda
Milano, G.; Fischel, J.L.; Etienne, M.C.; Renee, N.; Formento, P.; Thyss, A.; Gaspard, M.H.; Thill, L.; Cupissol, D.
Inhibition of dihydropyrimidine dehydrogenase by alpha-interferon: Experimental data on human tumor cell lines
Cancer Chemother. Pharmacol.
34
147-152
1994
Homo sapiens
brenda
Jiang, H.; Jiang, J.; Hu, P.; Hu, Y.
Measurement of endogenous uracil and dihydrouracil in plasma and urine of normal subjects by liquid chromatography-tandem mass spectrometry
J. Chromatogr. B
769
169-176
2002
Homo sapiens
brenda
Lin, L.L.; Hsu, W.H.; Hsu, W.Y.; Kan, S.C.; Hu, H.Y.
Phylogenetic analysis and biochemical characterization of a thermostable dihydropyrimidinase from alkaliphilic Bacillus sp. TS-23
Antonie van Leeuwenhoek
88
189-197
2005
Brevibacillus agri, Oryza sativa (Q6Z744), Salmonella enterica subsp. enterica serovar Typhimurium (Q8ZNL7)
brenda
Li, Y.; Mizutani, Y.; Shiraishi, T.; Nakamura, T.; Mikami, K.; Takaha, N.; Okihara, K.; Kawauchi, A.; Sakai, T.; Miki, T.
The significance of the expression of dihydropyrimidine dehydrogenase in prostate cancer
BJU Int.
99
663-668
2007
Homo sapiens
brenda
Ishikawa, M.; Miyauchi, T.; Kashiwagi, Y.
Clinical implications of thymidylate synthetase, dihydropyrimidine dehydrogenase and orotate phosphoribosyl transferase activity levels in colorectal carcinoma following radical resection and administration of adjuvant 5-FU chemotherapy
BMC Cancer
8
188
2008
Homo sapiens
brenda
Magne, N.; Etienne-Grimaldi, M.C.; Cals, L.; Renee, N.; Formento, J.L.; Francoual, M.; Milano, G.
Dihydropyrimidine dehydrogenase activity and the IVS14+1G>A mutation in patients developing 5FU-related toxicity
Br. J. Clin. Pharmacol.
64
237-240
2007
Homo sapiens
brenda
Sadahiro, S.; Suzuki, T.; Maeda, Y.; Ishikawa, K.; Tanaka, Y.; Yasuda, S.; Kamijo, A.; Makuuchi, H.; Murayama, C.
Dihydropyrimidine dehydrogenase activity during long-term adjuvant treatment with oral uracil and tegafur for colorectal cancer
Chemotherapy
53
442-445
2007
Homo sapiens
brenda
van Kuilenburg, A.B.; Klumpen, H.; Westermann, A.M.; Zoetekouw, L.; Van Lenthe, H.; Bakker, P.J.; Richel, D.J.; Guchelaar, H.
Increased dihydropyrimidine dehydrogenase activity associated with mild toxicity in patients treated with 5-fluorouracil and leucovorin
Eur. J. Cancer
43
459-465
2007
Homo sapiens
brenda
Yu, Z.; Yang, Q.; Sun, J.; Zhen, J.
Dihydropyrimidine dehydrogenase activity correlates with fluorouracil sensitivity in breast cancer
Exp. Oncol.
29
192-196
2007
Homo sapiens
brenda
Hayashi, T.; Kawahara, H.; Kobayashi, S.; Kashiwagi, H.; Hirai, K.; Yanaga, K.
Importance of thymidine phosphorylase, dihydropyrimidine dehydrogenase and thymidylate synthase expression at the invasive front of T3 rectal cancer as prognostic factors
Hepatogastroenterology
55
403-406
2008
Homo sapiens
brenda
Kumar, C.K.; Murthy, S.; Jamil, K.
Possible associations of splice site mutation of dihydropyrimidine dehydrogenase (IVS14+1G>A) in adverse drug reactions in some invasive ductal carcinoma patients
Int. J. Pharmacol.
3
130-136
2007
Homo sapiens
-
brenda
Honda, J.; Sasa, M.; Moriya, T.; Bando, Y.; Hirose, T.; Takahashi, M.; Nagao, T.; Tangoku, A.
Thymidine phosphorylase and dihydropyrimidine dehydrogenase are predictive factors of therapeutic efficacy of capecitabine monotherapy for breast cancer-preliminary results
J. Med. Invest.
55
54-60
2008
Homo sapiens
brenda
Kim, S.; Park, D.H.; Shim, J.
Thymidylate synthase and dihydropyrimidine dehydrogenase levels are associated with response to 5-fluorouracil in Caenorhabditis elegans
Mol. Cells
26
344-349
2008
Caenorhabditis elegans, Caenorhabditis elegans Bristol N2
brenda
Chikamatsu, K.; Shino, M.; Sakakura, K.; Nakajima, K.; Sakurai, T.; Miyashita, M.; Furuya, N.
Expression of thymidylate synthase and dihydropyrimidine dehydrogenase in adenoid cystic carcinoma of the head and neck: Correlation with clinical outcome
Oral Oncol.
43
662-669
2007
Homo sapiens
brenda
Zhang, X.; Diasio, R.B.
Regulation of human dihydropyrimidine dehydrogenase: implications in the pharmacogenetics of 5-FU-based chemotherapy
Pharmacogenomics
8
257-265
2007
Homo sapiens
brenda
Sulzyc-Bielicka, V.; Binczak-Kuleta, A.; Pioch, W.; Kladny, J.; Gziut, K.; Bielicki, D.; Ciechanowicz, A.
5-Fluorouracil toxicity-attributable IVS14+1G>A mutation of the dihydropyrimidine dehydrogenase gene in Polish colorectal cancer patients
Pharmacol. Rep.
60
238-242
2008
Homo sapiens
brenda
Yuan, D.; Wang, Q.; Gao, W.; Sheng, F.; Zhang, Z.; Lu, Q.; Cang, H.; Bi, R.
Cloning, expression, purification, characterization, crystallization and x-ray diffraction of bifunctional pyrimidine deaminase/reductase from Shigella flexneri 2a
Protein Pept. Lett.
14
925-927
2007
Shigella flexneri, Shigella flexneri 2a
brenda
Ben Fredj, R.; Gross, E.; Ben Ahmed, S.; Hassine, H.; Saguem, S.
The dihydrouracil/uracil ratio in plasma, clinical and genetic analysis for screening of dihydropyrimidine dehydrogenase deficiency in colorectal cancer patients treated with 5-fluorouracil
Pathol. Biol.
57
470-476
2009
Homo sapiens
brenda
Serve, K.M.; Darnell, J.L.; Takemoto, J.K.; Davies, N.M.; Black, M.E.
Validation of an isocratic HPLC method to detect 2-fluoro-beta-alanine for the analysis of dihydropyrimidine dehydrogenase activity
J. Chromatogr. B
878
1889-1892
2010
Homo sapiens
brenda
Hidese, R.; Mihara, H.; Kurihara, T.; Esaki, N.
Escherichia coli dihydropyrimidine dehydrogenase is a novel NAD-dependent heterotetramer essential for the production of 5,6-dihydrouracil
J. Bacteriol.
193
989-993
2011
Escherichia coli (P25889), Escherichia coli (P76440)
brenda
Baumel-Alterzon, S.; Weber, C.; Guillen, N.; Ankri, S.
Identification of dihydropyrimidine dehydrogenase as a virulence factor essential for the survival of Entamoeba histolytica in glucose-poor environments
Cell. Microbiol.
15
130-144
2013
Entamoeba histolytica, Entamoeba histolytica HM1:IMSS
brenda