Any feedback?
Literature summary for 2.7.1.105 extracted from
- 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 and 4 A pair of valves for fine-tuning of glucose metabolism in human cancer (2019), Mol. Metab., 20, 1-13 .
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| 1-(3-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one | - |
Homo sapiens |  |
| 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one | - |
Homo sapiens | |
| 5,6,7,8-tetrahydroxy-2-(4-hydroxyphenyl)chromen-4-one | - |
Homo sapiens | |
| 5-(N-(8-methoxy-4-quinolyl)amino)pentyl nitrate | - |
Homo sapiens | |
| 7,8-dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one | - |
Homo sapiens | |
| ethyl 7-hydroxy-2-oxo-2H-1-benzopyran-3-carboxylate | - |
Homo sapiens | |
| N-bromoacetylethanolamine phosphate | - |
Homo sapiens | |
| PFK-15 | i.e. 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one | Homo sapiens | |
| PFK-158 | potent and specific inhibitor | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| nucleus | PFKFB3 | Homo sapiens | 5634 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + beta-D-fructose 6-phosphate | Homo sapiens | - |
ADP + beta-D-fructose 2,6-bisphosphate | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | Q16875 | - |
- |
| Homo sapiens | Q16877 | - |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| phosphoprotein | phosphorylation of Ser461 by AMPK and Thr463 and Ser467 by CDK6 activates 6-phosphofructo-2-kinase activity and promotes glycolysis | Homo sapiens |
| side-chain modification | PCAF- and GCN5-mediated acetylation of Lys472/473 disrupts the NLS and sequesters PFKFB3 in the cytoplasm, facilitating its phosphorylation on Ser461 by AMPK. Polyubiquitination on Lys142 of PFKFB3 leads to proteasomal degradation of PFKFB3, shunting glucose metabolism from glycolysis to the PPP. Asymmetrical dimethylation on Arg131 and Arg134 stabilizes PFKFB3. Reduced methylation of PFKFB3 reroutes flux into the oxidative arm of PPP | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| acute myeloid leukemia cell | - |
Homo sapiens | - |
| astrocytoma cell | - |
Homo sapiens | - |
| breast cancer cell | - |
Homo sapiens | - |
| colonic cancer cell | - |
Homo sapiens | - |
| gastric cancer cell | - |
Homo sapiens | - |
| glioblastoma cell | - |
Homo sapiens | - |
| glioma cell | - |
Homo sapiens | - |
| HeLa cell | - |
Homo sapiens | - |
| hepatoma cell | - |
Homo sapiens | - |
| liver | - |
Homo sapiens | - |
| pancreatic cancer cell | - |
Homo sapiens | - |
| placenta | - |
Homo sapiens | - |
| prostate gland cancer cell | - |
Homo sapiens | - |
| small cell neuroendocrine carcinoma cell | - |
Homo sapiens | - |
| testis | - |
Homo sapiens | - |
| urinary bladder cancer cell | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + beta-D-fructose 6-phosphate | - |
Homo sapiens | ADP + beta-D-fructose 2,6-bisphosphate | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| Pfk-2 | - |
Homo sapiens |
| PFKFB3 | bifunctional enzyme with 6-phosphofructo-2-kinase and fructose-2,6-bisphosphatase activities | Homo sapiens |
| PFKFB4 | bifunctional enzyme with 6-phosphofructo-2-kinase and fructose-2,6-bisphosphatase activities | Homo sapiens |
Expression
| Organism | Comment | Expression |
|---|---|---|
| Homo sapiens | PFKFB3 is the major 6-phosphofructo-2-kinase isozymes overexpressed in human cancers | up |
| Homo sapiens | PFKFB4 is the major 6-phosphofructo-2-kinase isozymes overexpressed in human cancers | up |
General Information
| General Information | Comment | Organism |
|---|---|---|
| metabolism | PFKFB3 has the highest kinase:phosphatase ratio (710:1) to shunt glucose toward glycolysis, whereas PFKFB4 has more fructose-2,6-bisphosphatase-2 activity (kinase:phosphatase ratio of 4.6:1), redirecting glucose toward the pentose phosphate pathway, providing reducing power for lipid biosynthesis and scavenging reactive oxygen species. Co-expression of PFKFB3 and PFKFB4 provides sufficient glucose metabolism to satisfy the bioenergetics demand and redox homeostasis requirements of cancer cells | Homo sapiens |
| metabolism | PFKFB3 has the highest kinase:phosphatase ratio (710:1) to shunt glucose toward glycolysis, whereas PFKFB4 has more fructose-2,6-bisphosphatase-2 activity (kinase:phosphatase ratio of 4.6:1), redirecting glucose toward the pentose phosphate pathway, providing reducing power for lipid biosynthesis and scavenging reactive oxygen species. Co-expression of PFKFB3 and PFKFB4 provides sufficient glucose metabolism to satisfy the bioenergetics demand and redox homeostasis requirements of cancer cells. PFKFB4 acts as a protein kinase, regulates steroid receptor coactivator-3 activity and is involved in transcriptional regulation | Homo sapiens |
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
