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Chemical Compound Review

CHEMBL222824     4,6-dioxoheptanoic acid

Synonyms: CCRIS 1387, AG-K-75887, BSPBio_002406, KBioGR_001778, KBioGR_001852, ...
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Disease relevance of Succinylacetone


High impact information on Succinylacetone

  • Hereditary tyrosinemia and the heme biosynthetic pathway. Profound inhibition of delta-aminolevulinic acid dehydratase activity by succinylacetone [6].
  • Increased levels of the diagnostic metabolite succinylacetone in the urine of the Fah(6287SB) and Fah(5961SB) mutants indicate that these mutations cause a decrease in Fah enzymatic activity [7].
  • SA was shown to inhibit in vitro the overall DNA-ligase activity present in normal cell extracts [8].
  • These results suggest that accumulation of SA reduces the overall ligase activity in HT1 cells and indicate that metabolism errors may play a role in regulating enzymatic activities involved in DNA replication and repair [8].
  • In this pilot project, FAH was measured first, and, if necessary, succinylacetone was determined as the complementary test [9].

Chemical compound and disease context of Succinylacetone


Biological context of Succinylacetone


Anatomical context of Succinylacetone


Associations of Succinylacetone with other chemical compounds


Gene context of Succinylacetone

  • The MARE binding activity of Bach1 in K562 and MEL cells increased upon SA treatment, and the increase was diminished by the treatment with hemin [25].
  • SA had no effect on TfR expression in Fw cells [26].
  • Treatment of HLE/2E1 cells with succinylacetone (SA), a potent inhibitor of delta-aminolevulinate dehydratase and thereby heme synthesis, resulted in a further increase in ALAS-N mRNA but a decrease in HO-1 mRNA levels [27].
  • The addition of SA did not alter the c-myc response of ECFC to EP [28].
  • In short-term (1-2 hours) incubation, SA inhibited 59Fe incorporation from transferrin into heme, whereas total cellular 59Fe uptake was increased [26].

Analytical, diagnostic and therapeutic context of Succinylacetone


  1. Hereditary tyrosinemia. Formation of succinylacetone-amino acid adducts. Manabe, S., Sassa, S., Kappas, A. J. Exp. Med. (1985) [Pubmed]
  2. Augmentation of hematoporphyrin uptake and in vitro-growth inhibition of L1210 leukemia cells by succinylacetone. Ebert, P.S., Hess, R.A., Tschudy, D.P. J. Natl. Cancer Inst. (1985) [Pubmed]
  3. Fungal metabolic model for human type I hereditary tyrosinaemia. Fernández-Cañón, J.M., Peñalva, M.A. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  4. A heme-protein-based oxygen-sensing mechanism controls the expression and suppression of multiple proteins in anoxia-tolerant turtle hepatocytes. Land, S.C., Hochachka, P.W. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  5. Remodeling the regulation of iron metabolism during erythroid differentiation to ensure efficient heme biosynthesis. Schranzhofer, M., Schifrer, M., Cabrera, J.A., Kopp, S., Chiba, P., Beug, H., Müllner, E.W. Blood (2006) [Pubmed]
  6. Hereditary tyrosinemia and the heme biosynthetic pathway. Profound inhibition of delta-aminolevulinic acid dehydratase activity by succinylacetone. Sassa, S., Kappas, A. J. Clin. Invest. (1983) [Pubmed]
  7. Point mutations in the murine fumarylacetoacetate hydrolase gene: Animal models for the human genetic disorder hereditary tyrosinemia type 1. Aponte, J.L., Sega, G.A., Hauser, L.J., Dhar, M.S., Withrow, C.M., Carpenter, D.A., Rinchik, E.M., Culiat, C.T., Johnson, D.K. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  8. Deficient DNA-ligase activity in the metabolic disease tyrosinemia type I. Prieto-Alamo, M.J., Laval, F. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  9. Fumarylacetoacetase measurement as a mass-screening procedure for hereditary tyrosinemia type I. Laberge, C., Grenier, A., Valet, J.P., Morissette, J. Am. J. Hum. Genet. (1990) [Pubmed]
  10. Effects of succinylacetone on dimethylsulfoxide-mediated induction of heme pathway enzymes in mouse friend virus-transformed erythroleukemia cells. Beaumont, C., Deybach, J.C., Grandchamp, B., da Silva, V., de Verneuil, H., Nordmann, Y. Exp. Cell Res. (1984) [Pubmed]
  11. Succinyl acetone plus methotrexate as graft-versus-host disease prophylaxis in DLA-haploidentical canine littermate marrow grafts. Raff, R.F., Storb, R., Graham, T., Sale, G., Shulman, H., Pepe, M., Deeg, H.J., Schuening, F., Appelbaum, F.R., Fidler, J.M. Transplantation (1992) [Pubmed]
  12. Iron mobilization by succinylacetone methyl ester in rats. A model study for hereditary tyrosinemia and porphyrias characterized by 5-aminolevulinic acid overload. Rocha, M.E., Bandy, B., Costa, C.A., de Barros, M.P., Pinto, A.M., Bechara, E.J. Free Radic. Res. (2000) [Pubmed]
  13. Physiological basis for an animal model of the renal Fanconi syndrome: use of succinylacetone in the rat. Wyss, P.A., Boynton, S.B., Chu, J., Spencer, R.F., Roth, K.S. Clin. Sci. (1992) [Pubmed]
  14. Cyclin B-dependent kinase and caspase-1 activation precedes mitochondrial dysfunction in fumarylacetoacetate-induced apoptosis. Jorquera, R., Tanguay, R.M. FASEB J. (1999) [Pubmed]
  15. Bcl-XL induction during terminal differentiation of friend erythroleukaemia cells correlates with delay of apoptosis and loss of proliferative capacity but not with haemoglobinization. Hafid-Medheb, K., Poindessous-Jazat, V., Augery-Bourget, Y., Hanania, N., Robert-Lézénès, J. Cell Death Differ. (1999) [Pubmed]
  16. Processing and maturation of flavocytochrome b558 include incorporation of heme as a prerequisite for heterodimer assembly. DeLeo, F.R., Burritt, J.B., Yu, L., Jesaitis, A.J., Dinauer, M.C., Nauseef, W.M. J. Biol. Chem. (2000) [Pubmed]
  17. Immunosuppression by succinylacetone. II. Prevention of graft-vs-host disease. Hess, R.A., Tschudy, D.P., Blaese, R.M. J. Immunol. (1987) [Pubmed]
  18. The x-ray structure of yeast 5-aminolaevulinic acid dehydratase complexed with substrate and three inhibitors. Erskine, P.T., Newbold, R., Brindley, A.A., Wood, S.P., Shoolingin-Jordan, P.M., Warren, M.J., Cooper, J.B. J. Mol. Biol. (2001) [Pubmed]
  19. Distribution of iron in reticulocytes after inhibition of heme synthesis with succinylacetone: examination of the intermediates involved in iron metabolism. Richardson, D.R., Ponka, P., Vyoral, D. Blood (1996) [Pubmed]
  20. Iron distribution in Belgrade rat reticulocytes after inhibition of heme synthesis with succinylacetone. Garrick, L.M., Gniecko, K., Liu, Y., Cohan, D.S., Grasso, J.A., Garrick, M.D. Blood (1993) [Pubmed]
  21. Heme regulation of HeLa cell transferrin receptor number. Ward, J.H., Jordan, I., Kushner, J.P., Kaplan, J. J. Biol. Chem. (1984) [Pubmed]
  22. Glutathione propagates oxidative stress triggered by myeloperoxidase in HL-60 cells. Evidence for glutathionyl radical-induced peroxidation of phospholipids and cytotoxicity. Borisenko, G.G., Martin, I., Zhao, Q., Amoscato, A.A., Tyurina, Y.Y., Kagan, V.E. J. Biol. Chem. (2004) [Pubmed]
  23. A mouse model of renal tubular injury of tyrosinemia type 1: development of de Toni Fanconi syndrome and apoptosis of renal tubular cells in Fah/Hpd double mutant mice. Sun, M.S., Hattori, S., Kubo, S., Awata, H., Matsuda, I., Endo, F. J. Am. Soc. Nephrol. (2000) [Pubmed]
  24. Mechanism-based chemopreventive strategies against etoposide-induced acute myeloid leukemia: free radical/antioxidant approach. Kagan, V.E., Yalowich, J.C., Borisenko, G.G., Tyurina, Y.Y., Tyurin, V.A., Thampatty, P., Fabisiak, J.P. Mol. Pharmacol. (1999) [Pubmed]
  25. Heme positively regulates the expression of beta-globin at the locus control region via the transcriptional factor Bach1 in erythroid cells. Tahara, T., Sun, J., Nakanishi, K., Yamamoto, M., Mori, H., Saito, T., Fujita, H., Igarashi, K., Taketani, S. J. Biol. Chem. (2004) [Pubmed]
  26. Inhibition of heme synthesis decreases transferrin receptor expression in mouse erythroleukemia cells. Hradilek, A., Fuchs, O., Neuwirt, J. J. Cell. Physiol. (1992) [Pubmed]
  27. CYP2E1 overexpression up-regulates both non-specific delta-aminolevulinate synthase and heme oxygenase-1 in the human hepatoma cell line HLE/2E1. Takahashi, S., Takahashi, T., Mizobuchi, S., Matsumi, M., Yokoyama, M., Morita, K., Miyazaki, M., Namba, M., Akagi, R., Sassa, S. Int. J. Mol. Med. (2003) [Pubmed]
  28. Inhibition of heme synthesis induces apoptosis in human erythroid progenitor cells. Muta, K., Krantz, S.B. J. Cell. Physiol. (1995) [Pubmed]
  29. Pharmacologic, toxicologic, and marrow transplantation studies in dogs given succinyl acetone. Raff, R.F., Storb, R., Graham, T., Fidler, J.M., Sale, G.E., Johnston, B., Deeg, H.J., Pepe, M., Schuening, F., Appelbaum, F.R. Transplantation (1992) [Pubmed]
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