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Cat. Number
KA
Chemical Name
Koningic acid [KA]
CAS Number
57710-57-3
Mol. Formula
C15H20O5
Mol. Weight
280.32
Qty 1
5mg
Appearance
Koningic acid(KA)能抑制GAPDH活性,导致MG大量产生
References

Koningic acid (CAS No. 57710-57-3) (Figure 1) is a sesquiterpene lactone (molecular mass of 280.3) produced by the fungus Trichoderma koningii (1). Koningic acid inhibits glyceraldehyde 3-phosphate dehydrogenase (GAPDH) from various species by binding to the essential Cys residue in the catalytic site through a thioether bond (2-4). The covalent modification of the essential Cys by koningic acid leads to irreversible inactivation of GAPDH (2,3). The affinity of koningic binding to GAPDH for the inactivation is 1.6 μM (2).
Koningic acid is effective in inhibiting GAPDH of cells in culture at 10-50 μM (1,5). Koningic acid produces glucose-dependent ATP depletion in malignant cells (Figure 2) (5,6). There are many examples of the application of koningic acid in biochemical and biomedical researches (7-19).

< Reference>
1. Endo, A., K. Hasumi, et al. (1985). "Specific inhibition of glyceraldehyde-3-phosphate dehydrogenase by koningic acid
(heptelidic acid)." J Antibiot (Tokyo) 38(7): 920-5.
2. Sakai, K., K. Hasumi, et al. (1988). "Inactivation of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase by
koningic acid." Biochim Biophys Acta 952(3): 297-303.
3. Sakai, K., K. Hasumi, et al. (1991). "Identification of koningic acid (heptelidic acid)-modified site in rabbit muscle
glyceraldehyde-3-phosphate dehydrogenase." Biochim Biophys Acta 1077(2): 192-6.
4. Kato, M., K. Sakai, et al. (1992). "Koningic acid (heptelidic acid) inhibition of glyceraldehyde-3-phosphate
dehydrogenases from various sources." Biochim Biophys Acta 1120(1): 113-6.
5. Kumagai, S., R. Narasaki, et al. (2008). "Glucose-dependent active ATP depletion by koningic acid kills high-glycolytic
cells." Biochem Biophys Res Commun 365(2): 362-8.
6. Colell, A., D. R. Green, et al. (2009). "Novel roles for GAPDH in cell death and carcinogenesis." Cell Death Differ
16(12): 1573-81.
7. Markos, A., A. Miretsky, et al. (1993). "A glyceraldehyde-3-phosphate dehydrogenase with eubacterial features in the
amitochondriate eukaryote, Trichomonas vaginalis." J Mol Evol 37(6): 631-43.
8. McDonald, B., B. Reep, et al. (1993). "Glyceraldehyde-3-phosphate dehydrogenase is required for the transport of nitric
oxide in platelets." Proc Natl Acad Sci U S A 90(23): 11122-6.
9. Nakazawa, M., T. Uehara, et al. (1997). "Koningic acid (a potent glyceraldehyde-3-phosphate dehydrogenase
inhibitor)-induced fragmentation and condensation of DNA in NG108-15 cells." J Neurochem 68(6): 2493-9.
10. Nomura, Y. (1998). "A transient brain ischemia- and bacterial endotoxin-induced glial iNOS expression and
NO-induced neuronal apoptosis." Toxicol Lett 102-103: 65-9.
11. Beisswenger, P. J., S. K. Howell, et al. (2003). "Glyceraldehyde-3-phosphate dehydrogenase activity as an
independent modifier of methylglyoxal levels in diabetes." Biochim Biophys Acta 1637(1): 98-106.
12. Kim, J. H., S. Lee, et al. (2003). "Hydrogen peroxide induces association between glyceraldehyde 3-phosphate
dehydrogenase and phospholipase D2 to facilitate phospholipase D2 activation in PC12 cells." J Neurochem 85(5):
1228-36.
13. Takahashi, H., P. O. Tran, et al. (2004). "D-Glyceraldehyde causes production of intracellular peroxide in pancreatic
islets, oxidative stress, and defective beta cell function via non-mitochondrial pathways." J Biol Chem 279(36):
37316-23.
14. Gregus, Z. and B. Nemeti (2005). "The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase works as an
arsenate reductase in human red blood cells and rat liver cytosol." Toxicol Sci 85(2): 859-69.
15. Yasuda, Y., Y. Miyamoto, et al. (2006). "Mechanism of the stress-induced collapse of the Ran distribution." Exp Cell
Res 312(4): 512-20.
16. Nemeti, B. and Z. Gregus (2009). "Mechanism of thiol-supported arsenate reduction mediated by
phosphorolytic-arsenolytic enzymes: I. The role of arsenolysis." Toxicol Sci 110(2): 270-81.
17. Gregus, Z., G. Roos, et al. (2009). "Mechanism of thiol-supported arsenate reduction mediated by
phosphorolytic-arsenolytic enzymes: II. Enzymatic formation of arsenylated products susceptible for reduction to
arsenite by thiols." Toxicol Sci 110(2): 282-92.
18. Rogers, S. C., A. Said, et al. (2009). "Hypoxia limits antioxidant capacity in red blood cells by altering glycolytic
pathway dominance." FASEB J 23(9): 3159-70.
19. Zaid, H., I. Talior-Volodarsky, et al. (2009). "GAPDH binds GLUT4 reciprocally to hexokinase-II and regulates glucose transport activity." Biochem J 419(2): 475-84.

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