Target type: molecularfunction
Catalysis of the reaction: thymidine + phosphate = thymine + 2-deoxy-D-ribose 1-phosphate. [RHEA:16037]
Thymidine phosphorylase (TP) is an enzyme that catalyzes the reversible phosphorolysis of thymidine to thymine and deoxyribose-1-phosphate. This reaction plays a crucial role in the salvage pathway for pyrimidine bases, which is essential for DNA synthesis and repair. TP is also involved in the degradation of thymidine, a nucleoside found in DNA, and in the regulation of intracellular thymidine levels. The enzyme exhibits broad substrate specificity, being able to process a wide range of pyrimidine nucleosides, including uridine, cytidine, and deoxyuridine. TP is a dimeric protein composed of two identical subunits, each containing a pyrimidine nucleoside-binding site and a phosphate-binding site. The active site of TP is located at the interface between the two subunits and is characterized by a highly conserved amino acid sequence. The mechanism of TP catalysis involves a two-step process. In the first step, the enzyme binds both the pyrimidine nucleoside and phosphate, forming a ternary complex. In the second step, the nucleoside is cleaved by the enzyme, releasing the free base and deoxyribose-1-phosphate. The reaction is reversible, allowing for the synthesis of thymidine from thymine and deoxyribose-1-phosphate. The activity of TP is regulated by a variety of factors, including pH, temperature, and the presence of inhibitors. TP is widely distributed in various tissues and organisms, including bacteria, yeast, plants, and animals. In humans, TP is expressed in a variety of tissues, including the liver, kidney, and small intestine. TP has been implicated in a number of biological processes, including cell proliferation, angiogenesis, and tumor growth. The enzyme has also been proposed as a target for the development of new anticancer drugs.'
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Protein | Definition | Taxonomy |
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Thymidine phosphorylase | A thymidine phosphorylase that is encoded in the genome of Escherichia coli K-12. [OMA:P07650, PRO:DNx] | Escherichia coli K-12 |
Uridine phosphorylase 1 | A uridine phosphorylase 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q16831] | Homo sapiens (human) |
Thymidine phosphorylase | A thymidine phosphorylase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P19971] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
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thymidine | pyrimidine 2'-deoxyribonucleoside | Escherichia coli metabolite; human metabolite; metabolite; mouse metabolite | |
floxuridine | floxuridine : A pyrimidine 2'-deoxyribonucleoside compound having 5-fluorouracil as the nucleobase; used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract. Floxuridine: An antineoplastic antimetabolite that is metabolized to fluorouracil when administered by rapid injection; when administered by slow, continuous, intra-arterial infusion, it is converted to floxuridine monophosphate. It has been used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract. | nucleoside analogue; organofluorine compound; pyrimidine 2'-deoxyribonucleoside | antimetabolite; antineoplastic agent; antiviral drug; radiosensitizing agent |
idoxuridine | organoiodine compound; pyrimidine 2'-deoxyribonucleoside | antiviral drug; DNA synthesis inhibitor | |
bromodeoxyuridine | Bromodeoxyuridine: A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors. | pyrimidine 2'-deoxyribonucleoside | antimetabolite; antineoplastic agent |
trifluridine | trifluridine : A pyrimidine 2'-deoxyribonucleoside compound having 5-trifluoromethyluracil as the nucleobase. An antiviral drug used mainly in the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis. Trifluridine: An antiviral derivative of THYMIDINE used mainly in the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis due to HERPES SIMPLEX virus. (From Martindale, The Extra Pharmacopoeia, 30th ed, p557) | nucleoside analogue; organofluorine compound; pyrimidine 2'-deoxyribonucleoside | antimetabolite; antineoplastic agent; antiviral drug; EC 2.1.1.45 (thymidylate synthase) inhibitor |
deoxyuridine | pyrimidine 2'-deoxyribonucleoside | Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite | |
doxifluridine | doxifluridine : A pyrimidine 5'-deoxyribonucleoside that is 5-fluorouridine in which the hydroxy group at the 5' position is replaced by a hydrogen. It is an oral prodrug of the antineoplastic agent 5-fluorouracil. Designed to circumvent the rapid degradation of 5-fluorouracil by dihydropyrimidine dehydrogenase in the gut wall, it is converted into 5-fluorouracil in the presence of pyrimidine nucleoside phosphorylase. | organofluorine compound; pyrimidine 5'-deoxyribonucleoside | antimetabolite; antineoplastic agent; prodrug |
captopril | captopril : A L-proline derivative in which L-proline is substituted on nitrogen with a (2S)-2-methyl-3-sulfanylpropanoyl group. It is used as an anti-hypertensive ACE inhibitor drug. Captopril: A potent and specific inhibitor of PEPTIDYL-DIPEPTIDASE A. It blocks the conversion of ANGIOTENSIN I to ANGIOTENSIN II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the RENIN-ANGIOTENSIN SYSTEM and inhibits pressure responses to exogenous angiotensin. | alkanethiol; L-proline derivative; N-acylpyrrolidine; pyrrolidinemonocarboxylic acid | antihypertensive agent; EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor |
5-benzylacyclouridine | 5-benzyl-1-(2-hydroxyethoxymethyl)uracil : A pyrimidone that is uracil which is substituted by a 2-hydroxyethoxymethyl group at position 1 and a benzyl group at position 5. 5-benzylacyclouridine: structure given in first source | hydroxyether; primary alcohol; pyrimidone | |
2',3'-dideoxythymidine | |||
6-aminothymine | 6-aminothymine: inhibits degradation of nucleosides (idoxuridine, thymidine) & pyrimidine bases | ||
5-chloro-2'-deoxyuridine | |||
5-(2-propenyl)-2'-deoxyuridine | |||
edoxudin | pyrimidine 2'-deoxyribonucleoside | ||
3-cyano-6-hydroxy-4-methyl-2-pyridone | 3-cyano-6-hydroxy-4-methyl-2-pyridone: structure in first source | ||
6-amino-5-bromouracil | |||
5-hydroxymethyl-2'-deoxyuridine | pyrimidine 2'-deoxyribonucleoside | ||
5-formyl-2'-deoxyuridine | 5-formyl-2'-deoxyuridine: structure given in first source | ||
2,6-dihydroxy-3-cyanopyridine | 2,6-dihydroxy-3-cyanopyridine: inhibitor of 5-fluorouracil degradation | ||
5-nitro-2'-deoxyuridine | |||
5-cyano-2'-deoxyuridine | 5-cyano-2'-deoxyuridine: structure in first source | ||
5-phenyl-1,3,4-oxadiazole-2-thiol | 5-phenyl-1,3,4-oxadiazole-2-thiol: structure in first source | ||
ma-1 | tipiracil : A member of the class of pyrimidones that is uracil substituted by chloro and (2-iminopyrrolidin-1-yl)methyl groups at positions 5 and 6 respectively. Used (as the hydrochloride salt) in combination with trifluridine, a nucleoside metabolic inhibitor, for treatment of advanced/relapsed unresectable colorectal cancer. tipiracil: inhibits thymidine phosphorylase | carboxamidine; organochlorine compound; pyrimidone; pyrrolidines | antineoplastic agent; EC 2.4.2.4 (thymidine phosphorylase) inhibitor |
5-(1-propenyl)-2'-deoxyuridine | 5-(1-propenyl)-2'-deoxyuridine: has anti-herpes activity; structure in first source | ||
5-chloro-6-(1-(2-iminopyrrolidinyl) methyl)uracil hydrochloride | tipiracil hydrochloride : A hydrochloride obtained by combining tipiracil with one equivalent of hydrochloric acid. Used in combination with trifluridine, a nucleoside metabolic inhibitor, for treatment of advanced/relapsed unresectable colorectal cancer. | hydrochloride; iminium salt | antineoplastic agent; EC 2.4.2.4 (thymidine phosphorylase) inhibitor |
sesone | 7-deazaxanthine: structure in first source | ||
5'-o-tritylinosine | 5'-O-tritylinosine: structure in first source |