Details of Drug-Metabolizing Enzyme (DME)

General Information of DME (ID: DMEN004)
DME Name Dihydropyrimidinase (DPYS), Homo sapiens
Gene Name DPYS
UniProt ID
DPYS_HUMAN
EC Number    EC: 2.7.1.113     (Click to Show/Hide the Complete EC Tree)
Transferase
Kinase
Phosphotransferase
EC: 2.7.1.113
Lineage    Species: Homo sapiens     (Click to Show/Hide the Complete Species Lineage)
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
      Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Pathway/Function) of This DME
Sequence
MAAPSRLLIRGGRVVNDDFSEVADVLVEDGVVRALGHDLLPPGGAPAGLRVLDAAGKLVL
PGGIDTHTHMQFPFMGSRSIDDFHQGTKAALSGGTTMIIDFAIPQKGGSLIEAFETWRSW
ADPKVCCDYSLHVAVTWWSDQVKEEMKILVQDKGVNSFKMFMAYKDLYMVTDLELYEAFS
RCKEIGAIAQVHAENGDLIAEGAKKMLALGITGPEGHELCRPEAVEAEATLRAITIASAV
NCPLYIVHVMSKSAAKVIADARRDGKVVYGEPIAASLGTDGTHYWNKEWHHAAHHVMGPP
LRPDPSTPDFLMNLLANDDLTTTGTDNCTFNTCQKALGKDDFTKIPNGVNGVEDRMSVIW
EKGVHSGKMDENRFVAVTSTNAAKIFNLYPRKGRIAVGSDADIVIWDPKGTRTISAKTHH
QAVNFNIFEGMVCHGVPLVTISRGKVVYEAGVFSVTAGDGKFIPRKPFAEYIYKRIKQRD
RTCTPTPVERAPYKGEVATLKSRVTKEDATAGTRKQAHP
Structure
2VR2 ;
Function Catalyzes the second step of the reductive pyrimidine degradation, the reversible hydrolytic ring opening of dihydropyrimidines. Can catalyze the ring opening of 5,6-dihydrouracil to N-carbamyl-alanine and of 5,6-dihydrothymine to N-carbamyl-amino isobutyrate.
Full List of Drug(s) Metabolized by This DME
      Drugs Approved by FDA Click to Show/Hide the Full List of Drugs:          3 Drugs
Dexrazoxane hydrochloride
 Drug Info Approved Breast cancer ICD11: 2C60 [1]
Capecitabine
 Drug Info Approved Colon cancer ICD11: 2B90 [2]
Floxuridine
 Drug Info Approved Hepatocellular carcinoma ICD11: 2C12 [3]
Full List of Metabolic Reactions (MR) Catalyzed by This DME
MR ID Reactant Product MR Type Source Drug REF
MR002525 FUH2 FUPA Hydrolysis - Hydrolysis Capecitabine [4]
MR002598 Dexrazoxane hydrochloride Dexrazoxane metabolite B Hydrolysis - Hydrolysis Dexrazoxane hydrochloride [1], [5]
MR002599 Dexrazoxane hydrochloride Dexrazoxane metabolite C Hydrolysis - Hydrolysis Dexrazoxane hydrochloride [1], [5]
MR001056 5,6-Dihydro-5-fluorouracil Fluoro-beta-ureidopropionate Hydrolysis - Hydrolysis Floxuridine [6], [3]
References
1 Metabolism of the cardioprotective drug dexrazoxane and one of its metabolites by isolated rat myocytes, hepatocytes, and blood. Drug Metab Dispos. 2005 Jun;33(6):719-25.
2 LABEL: RIZATRIPTAN BENZOATE
3 The achievement of mass balance by simultaneous quantification of floxuridine prodrug, floxuridine, 5-fluorouracil, 5-dihydrouracil, -fluoro--ureidopropionate, -fluoro--alanine using LC-MS J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Apr 15;879(13-14):915-20. doi: 10.1016/j.jchromb.2011.02.045.
4 A new, validated HPLC-MS/MS method for the simultaneous determination of the anti-cancer agent capecitabine and its metabolites: 5'-deoxy-5-fluorocytidine, 5'-deoxy-5-fluorouridine, 5-fluorouracil and 5-fluorodihydrouracil, in human plasma
5 Clinically Translatable Prevention of Anthracycline Cardiotoxicity by Dexrazoxane Is Mediated by Topoisomerase II Beta and Not Metal Chelation. Circ Heart Fail. 2021 Nov;14(11):e008209. doi: 10.1161/CIRCHEARTFAILURE.120.008209.
6 Enhanced cancer cell growth inhibition by dipeptide prodrugs of floxuridine: increased transporter affinity and metabolic stability. Mol Pharm. 2008 Sep-Oct;5(5):717-27.

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