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Literature summary for 2.4.2.4 extracted from
- Distinct substrate specificity and physicochemical characterization of native human hepatic thymidine phosphorylase (2018), PLoS ONE, 13, e0202826 .
Application
| Application | Comment | Organism |
|---|---|---|
| medicine | thymidine phosphorylase is involved regulation of intra- or extracellular thymidine concentration, angiogenesis, cancer chemotherapy, radiotherapy, as well as tumor imaging | Homo sapiens |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.2 | - |
5'-deoxy-5-fluorouridine | pH 8.0, 37°C | Homo sapiens |  |
| 0.275 | - |
uridine | pH 8.0, 37°C | Homo sapiens | |
| 0.285 | - |
thymidine | pH 8.0, 37°C | Homo sapiens | |
| 0.325 | - |
5-fluoro-2'-deoxyuridine | pH 8.0, 37°C | Homo sapiens | |
| 0.735 | - |
2'-deoxyuridine | pH 8.0, 37°C | Homo sapiens | |
| 1.3 | - |
5-fluorouridine | pH 8.0, 37°C | Homo sapiens | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytosol | - |
Homo sapiens | 5829 | - |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 100000 | - |
gel filtration | Homo sapiens |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| thymidine + phosphate | Homo sapiens | - |
thymine + 2-deoxy-alpha-D-ribose 1-phosphate | - |
r | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | P19971 | - |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| native enzyme 5130fold from liver cytosol to apparent homogeneity by anion exchange and hydrophobic interaction chromatography, and dialysis, followed by hydroxyapatite chromatography | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| liver | the liver is the major site of pyrimidine metabolism and contains high levels of thymidine phosphorylase (TP) | Homo sapiens | - |
| additional information | molecular weight and homodimer structure of human hepatic enzyme is similar to those of the enzymes from human amniochorion, blood platelet, placenta, psoriatic lesions, and the recombinant enzyme from a colorectal tumor. Detection by human placenta TP antisera binding to various preparations of hepatic TP | Homo sapiens | - |
Specific Activity [micromol/min/mg]
| Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
|---|---|---|---|
| 0.114 | - |
purified native enzyme, pH 8.0, 37°C, substrate uridine | Homo sapiens |
| 1.5 | - |
purified native enzyme, pH 8.0, 37°C, substrate 5-fluorouridine or 5'-deoxy-5-fluorouridine | Homo sapiens |
| 5.55 | - |
purified native enzyme, pH 8.0, 37°C, substrate thymidine | Homo sapiens |
| 8.1 | - |
purified native enzyme, pH 8.0, 37°C, substrate 5-fluoro-2'-deoxyuridine | Homo sapiens |
| 8.91 | - |
purified native enzyme, pH 8.0, 37°C, substrate 2'-deoxyuridine | Homo sapiens |
| 18480 | - |
purified native enzyme, pH 8.0, 37°C | Homo sapiens |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 2'-deoxyuridine + phosphate | - |
Homo sapiens | uracil + 2-deoxy-alpha-D-ribose 1-phosphate | - |
r | |
| 5'-deoxy-5-fluorouridine + phosphate | - |
Homo sapiens | 5-fluorouracil + 5-deoxy-alpha-D-ribose 1-phosphate | - |
r | |
| 5-fluoro-2'-deoxyuridine + phosphate | - |
Homo sapiens | 5-fluorouracil + 2-deoxy-alpha-D-ribose 1-phosphate | - |
r | |
| 5-fluorouridine + phosphate | - |
Homo sapiens | 5-fluorouracil + alpha-D-ribose 1-phosphate | - |
r | |
| additional information | substrate specificity, overview | Homo sapiens | ? | - |
- |
|
| thymidine + phosphate | - |
Homo sapiens | thymine + 2-deoxy-alpha-D-ribose 1-phosphate | - |
r | |
| uridine + phosphate | - |
Homo sapiens | uracil + alpha-D-ribose 1-phosphate | - |
r | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| homodimer | 2 * 52000, SDS-PAGE, 2 * 49885, sedimentation equilibrium analysis, 2 * 49785-49882, mass spectrometry (2 methods) | Homo sapiens |
| More | modeling of monomer-dimer-tetramer transition, for the transition model of the subunits aggregation, the non-linear regression fitting yielded the equilibrium association constants (Ka) in absorbance units. Amino acid sequence determination, overview | Homo sapiens |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 37 | - |
assay at | Homo sapiens |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 8 | - |
assay at | Homo sapiens |
pI Value
| Organism | Comment | pI Value Maximum | pI Value |
|---|---|---|---|
| Homo sapiens | isoelectric focusing | - |
4.3 |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | the enzyme is identical to the platelet-derived endothelial cell growth factor (PD-ECGF). Amino acid sequence homology between hepatic thymidine phosphorylase and PD-ECGF | Homo sapiens |
| malfunction | mutation of the TP gene is associated with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), an autosomal recessive human disease exhibiting multiple deletions of skeletal muscle mitochondrial DNA (peripheral neuropathy, myopathy, leukoencephalopathy, lactic acidosis, gastrointestinal dysmotility, progressive external ophthalmoplegia, and thin body habitus) | Homo sapiens |
| physiological function | thymidine phosphorylase is an important enzyme of the pyrimidine salvage pathways. It catalyzes the reversible phosphorolysis of thymidine, deoxyuridine, but not deoxycytidine, and their analogues, to their respective nucleobases and 2-deoxy-alpha-D-ribose-1-phosphate. The biological significance of TP has several aspects. It has a role in maintaining the integrity of the blood vessels, and its activity is an essential step in the regulation of intra- or extracellular thymidine concentration and homeostasis in mammalian cells. The enzyme is identical to the platelet-derived endothelial cell growth factor (PD-ECGF) which is involved in the process of angiogenesis, neoplastic tissue growth, and metastases. Thymidine phosphorylase is involved regulation of intra- or extracellular thymidine concentration and angiogenesis | Homo sapiens |
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