Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

2.4.2.4

Official Name

thymidine phosphorylase

Name from literature

Thymidine phosphorylase

Pathway from literature

etabolizes 5'-deoxy-5-fluorouridine (5'-dFUrd,doxifluridine)

Pathway from KEGG

Human Diseases; Cancers; Bladder cancer; map05219

Nucleotide Metabolism; Purine metabolism; map00230

Xenobiotics Biodegradation and Metabolism; Drug metabolism - other enzymes; map00983

Nucleotide Metabolism; Pyrimidine metabolism; map00240

Organisms

Human (9606)

Genome localization

22q13|22q13.33[1890 ],

Comments

The enzyme in some tissues also catalyses deoxyribosyltransferase reactions of the type catalysed by EC 2.4.2.6, nucleoside deoxyribosyltransferase.

Rate-limiting Description

"This is most likely attributable to the upregulation of thymidine phosphorylase (the rate-limiting enzyme needed to convert capecitabine to 5-fluorouracil ." (5-FU) in tumor cells following radiotherapy)

"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)

"The most important are the major target enzyme, thymidylate synthase (TS) and the rate limiting enzyme in the degradation pathway, dihydropyrimidine dehydrogenase (DPD), equally important for the analogue capecitabine is thymidine phosphorylase (TP), which is rate limiting for activation of this prodrug." (15134221)

Regulatory Information

Upstream transcription factor

6667

Regulatory type

Detail

transcriptional factor;Sp1(6667)

"Sp1 transcription factor contributes to its expression in human colon carcinoma cells." (12466967)

key enzyme;

"As demonstrated using ELISA or immunohistochemistry, oxaliplatin in xenograft model tumors up-regulated the level of thymidine phosphorylase (dThdPase), a key enzyme for the metabolism of capecitabine to 5-fluorouracil." (17786335)

transcriptional factor;Sp1(6667)

"Sp1 transcription factor contributes to its expression in human colon carcinoma cells." (12466967)

signal pathway;

"cytoprotective function of TP is mediated, at least in part, by regulation of the PI3K/Akt pathway; TP molecules confer resistance to DNA damage-induced apoptosis in cancer cells" (16458893)

Gene ontology

Gene ontology

GO:0043231 (C) intracellular membrane-bounded organelle [P19971 ];
GO:0005161 (F) platelet-derived growth factor receptor bin... [P19971 ];
GO:0001525 (P) angiogenesis [P19971 ];
GO:0009032 (F) thymidine phosphorylase activity [P19971 ];
GO:0005829 (C) cytosol [P19971 ];
GO:0008083 (F) growth factor activity [P19971 ];
GO:0030154 (P) cell differentiation [P19971 ];
GO:0000002 (P) mitochondrial genome maintenance [P19971 ];
GO:0006220 (P) pyrimidine nucleotide metabolic process [P19971 ];
GO:0006935 (P) chemotaxis [P19971 ];
GO:0006206 (P) pyrimidine base metabolic process [P19971 ];
GO:0006260 (P) DNA replication [P19971 ];
GO:0006213 (P) pyrimidine nucleoside metabolic process [P19971 ];

Disease relevance

Disease

Defects in TYMP are the cause of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) [MIM:603041];
also known as myoneurogastrointestinal encephalomyopathy. MNGIE is an autosomal recessive disease associated with multiple deletions of skeletal muscle mitochondrial DNA (MtDNA). It is clinically characterized by onset between the second and fifth decades of life, ptosis, progressive external ophthalmoplegia, gastrointestinal dysmotility (often pseudoobstruction), diffuse leukoencephalopathy, thin body habitus, peripheral neuropathy, and myopathy [P19971 ];

Links

SwissProt

B3KQ24; P19971

Entrez Gene

1890

HPRD

08833



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  Last Modified: 2009-03-24  
  Design by Zhao Min