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Literature summary for 2.7.1.40 extracted from
- Vitamin K3 and K5 are inhibitors of tumor pyruvate kinase M2 (2012), Cancer Lett., 316, 204-210.
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| expression of His6-tagged isozymes in Escherichia coli | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| 4-amino-2-methylnaphthalen-1-ol | i.e. vitamin K5, shows a significantly stronger potency to inhibit isozyme PKM2 than to inhibit isozymes PKM1 and PKL | Homo sapiens |  |
| menadione | i.e. vitamin K3, shows a significantly stronger potency to inhibit isozyme PKM2 than to inhibit isozymes PKM1 and PKL | Homo sapiens | |
| additional information | D-fructose 1,6-bisphosphate diminishes the inhibitory effects of vitamin K derivatives. No inhibition of isozyme PKM2 by vitamin K1 and vitamin K2 | Homo sapiens | |
| N-(3-carboxy-4-hydroxy)phenyl-2,5-dimethylpyrrole | a PKM2 inhibitor | Homo sapiens | |
| shikonin | a PKM2 inhibitor | Homo sapiens | |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | required | Homo sapiens | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + pyruvate | Homo sapiens | - |
ADP + phosphoenolpyruvate | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant His6-tagged isozymes from Escherichia coli by nickel affinity chromatgraphy | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| HeLa cell | Hela cells express PKM2 but not PKM1 or PKL | Homo sapiens | - |
| liver | isozyme PKL | Homo sapiens | - |
| additional information | isozyme PKM1 is expressed in most adult tissues | Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + pyruvate | - |
Homo sapiens | ADP + phosphoenolpyruvate | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| PKL | - |
Homo sapiens |
| PKM1 | - |
Homo sapiens |
| PKM2 | - |
Homo sapiens |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 25 | - |
assay at | Homo sapiens |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.5 | - |
assay at | Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Homo sapiens | |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.028 | - |
pH 7.5, 25°C, recombinant His6-tagged isozyme PKM2, in absence of D-fructose 1,6-bisphosphate | Homo sapiens | 4-amino-2-methylnaphthalen-1-ol | |
| 0.045 | - |
pH 7.5, 25°C, recombinant His6-tagged isozyme PKM2, in presence of D-fructose 1,6-bisphosphate | Homo sapiens | 4-amino-2-methylnaphthalen-1-ol | |
| 0.0593 | - |
pH 7.5, 25°C, recombinant His6-tagged isozyme PKM2, in absence of D-fructose 1,6-bisphosphate | Homo sapiens | N-(3-carboxy-4-hydroxy)phenyl-2,5-dimethylpyrrole | |
| 0.0775 | - |
pH 7.5, 25°C, recombinant His6-tagged isozyme PKM2, in presence of D-fructose 1,6-bisphosphate | Homo sapiens | N-(3-carboxy-4-hydroxy)phenyl-2,5-dimethylpyrrole | |
| 0.12 | - |
pH 7.5, 25°C, recombinant His6-tagged isozyme PKL, in absence of D-fructose 1,6-bisphosphate | Homo sapiens | 4-amino-2-methylnaphthalen-1-ol | |
| 0.15 | - |
pH 7.5, 25°C, recombinant His6-tagged isozyme PKM2, in absence of D-fructose 1,6-bisphosphate | Homo sapiens | menadione | |
| 0.191 | - |
pH 7.5, 25°C, recombinant His6-tagged isozyme PKM1, in absence of D-fructose 1,6-bisphosphate | Homo sapiens | 4-amino-2-methylnaphthalen-1-ol | |
| 0.381 | - |
pH 7.5, 25°C, recombinant His6-tagged isozyme PKM2, in presence of D-fructose 1,6-bisphosphate | Homo sapiens | menadione | |
| 0.837 | - |
pH 7.5, 25°C, recombinant His6-tagged isozyme PKL, in absence of D-fructose 1,6-bisphosphate | Homo sapiens | menadione | |
| 3.407 | - |
pH 7.5, 25°C, recombinant His6-tagged isozyme PKM1, in absence of D-fructose 1,6-bisphosphate | Homo sapiens | menadione | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | consequence of PKM2 inhibition is a reduced glycolytic flux, which can be reflected by the rates of cellular glucose consumption and lactate production | Homo sapiens |
| physiological function | pyruvate kinase isozyme PKM2 is a rate-limiting enzyme of aerobic glycolysis in cancer cells and plays important roles in cancer metabolism and growth. Vitamin K3/vitamin K5-enhanced toxicity of doxorubicin is associated with pyruvate kinase activity | Homo sapiens |
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