| Record Information |
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| Version | 2.0 |
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| Created at | 2005-11-16 15:48:42 UTC |
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| Updated at | 2021-08-19 23:58:27 UTC |
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| NP-MRD ID | NP0000774 |
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| Secondary Accession Numbers | None |
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| Natural Product Identification |
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| Common Name | Succinylacetone |
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| Description | Succinylacetone, also known as 4,6-dioxoheptanoic acid or SUAC, belongs to the class of compounds known as medium-chain keto acids and derivatives. These are keto acids with 6 to 12 carbon atoms. Succinylacetone is soluble (in water) and a weakly acidic compound (based on its pKa). Succinylacetone has been detected in amniotic fluid, blood, and urine. Within the cell, succinylacetone is primarily located in the cytoplasm (predicted from logP). Succinylacetone can be created by the oxidation of glycine, and is a precursor of methylglyoxal (Wikipedia). Succinylacetone is an abnormal tyrosine metabolite that arises from defects in the enzyme called fumarylacetoacetase (PMID: 16448836 ). Fumarylacetoacetase normally catalyzes the hydrolysis of 4-fumarylacetoacetate into fumarate and acetoacetate. If present in sufficiently high levels, succinylacetone can act as an acidogen, an oncometabolite, and a metabotoxin. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. An oncometabolite is an endogenous metabolite that causes cancer. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of succinylacetone are associated with tyrosinemia type I. Type I tyrosinemia is an inherited metabolism disorder due to a shortage of the enzyme fumarylacetoacetate hydrolase that is needed to break down tyrosine. Patients usually develop features such as hepatic necrosis, renal tubular injury, and hypertrophic cardiomyopathy. Neurologic and dermatologic manifestations are also possible. The urine has an odour of cabbage or rancid butter. Succinylacetone is a keto-acid, which is a subclass of organic acids. Abnormally high levels of organic acids in the blood (organic acidemia), urine (organic aciduria), the brain, and other tissues lead to general metabolic acidosis. Acidosis typically occurs when arterial pH falls below 7.35. In infants with acidosis, the initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These can progress to heart, liver, and kidney abnormalities, seizures, coma, and possibly death. These are also the characteristic symptoms of untreated tyrosinemia. Many affected children with organic acidemias experience intellectual disability or delayed development. Succinylacetone appears to function as an oncometabolite (similar in function to succinate, another oncometabolite) as patients with high levels of this compound often develop hepatocellular carcinoma (PMID: 20003495 ). |
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| Structure | InChI=1S/C7H10O4/c1-5(8)4-6(9)2-3-7(10)11/h2-4H2,1H3,(H,10,11) |
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| Synonyms | | Value | Source |
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| 4,6-Dioxoheptanoate | HMDB | | 4,6-Dioxoheptanoic acid | HMDB | | Succinylacetone | ChEBI |
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| Chemical Formula | C7H10O4 |
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| Average Mass | 158.1519 Da |
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| Monoisotopic Mass | 158.05791 Da |
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| IUPAC Name | 4,6-dioxoheptanoic acid |
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| Traditional Name | succinylacetone |
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| CAS Registry Number | 51568-18-4 |
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| SMILES | CC(=O)CC(=O)CCC(O)=O |
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| InChI Identifier | InChI=1S/C7H10O4/c1-5(8)4-6(9)2-3-7(10)11/h2-4H2,1H3,(H,10,11) |
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| InChI Key | WYEPBHZLDUPIOD-UHFFFAOYSA-N |
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| Experimental Spectra |
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| | Spectrum Type | Description | Depositor Email | Depositor Organization | Depositor | Deposition Date | View |
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| 1D NMR | 1H NMR Spectrum (1D, 500 MHz, 5%_DMSO, experimental) | Wishart Lab | Wishart Lab | David Wishart | 2021-06-20 | View Spectrum | | 2D NMR | [1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental) | Wishart Lab | Wishart Lab | David Wishart | 2021-06-20 | View Spectrum |
| | Predicted Spectra |
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| Not Available | | Chemical Shift Submissions |
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| Not Available | | Species |
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| Species of Origin | |
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| Species Where Detected | |
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| Chemical Taxonomy |
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| Description | Belongs to the class of organic compounds known as medium-chain keto acids and derivatives. These are keto acids with a 6 to 12 carbon atoms long side chain. |
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| Kingdom | Organic compounds |
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| Super Class | Organic acids and derivatives |
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| Class | Keto acids and derivatives |
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| Sub Class | Medium-chain keto acids and derivatives |
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| Direct Parent | Medium-chain keto acids and derivatives |
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| Alternative Parents | |
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| Substituents | - Medium-chain keto acid
- Gamma-keto acid
- 1,3-diketone
- 1,3-dicarbonyl compound
- Ketone
- Monocarboxylic acid or derivatives
- Carboxylic acid
- Carboxylic acid derivative
- Organic oxygen compound
- Organic oxide
- Hydrocarbon derivative
- Organooxygen compound
- Carbonyl group
- Aliphatic acyclic compound
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| Molecular Framework | Aliphatic acyclic compounds |
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| External Descriptors | Not Available |
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| Physical Properties |
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| State | Solid |
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| Experimental Properties | | Property | Value | Reference |
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| Melting Point | 66 - 67 °C | Not Available | | Boiling Point | Not Available | Not Available | | Water Solubility | 257900 mg/L @ 25 °C (est) | The Good Scents Company Information System | | LogP | Not Available | Not Available |
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| Predicted Properties | |
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| General References | - Fernandez-Canon JM, Baetscher MW, Finegold M, Burlingame T, Gibson KM, Grompe M: Maleylacetoacetate isomerase (MAAI/GSTZ)-deficient mice reveal a glutathione-dependent nonenzymatic bypass in tyrosine catabolism. Mol Cell Biol. 2002 Jul;22(13):4943-51. [PubMed:12052898 ]
- Laberge C, Lescault A, Grenier A, Morrisette J, Gagne R, Gadbois P, Halket J: Oral loading of homogentisic acid in controls and in obligate heterozygotes for hereditary tyrosinemia type I. Am J Hum Genet. 1990 Aug;47(2):329-37. [PubMed:2378359 ]
- Poudrier J, Lettre F, St-Louis M, Tanguay RM: Genotyping of a case of tyrosinaemia type I with normal level of succinylacetone in amniotic fluid. Prenat Diagn. 1999 Jan;19(1):61-3. [PubMed:10073910 ]
- Jakobs C, Dorland L, Wikkerink B, Kok RM, de Jong AP, Wadman SK: Stable isotope dilution analysis of succinylacetone using electron capture negative ion mass fragmentography: an accurate approach to the pre- and neonatal diagnosis of hereditary tyrosinemia type I. Clin Chim Acta. 1988 Feb 15;171(2-3):223-31. [PubMed:3286060 ]
- Kimura A, Endo F, Kagimoto S, Inoue T, Suzuki M, Kurosawa T, Tohma M, Fujisawa T, Kato H: Tyrosinemia type I-like disease: a possible manifestation of 3-oxo-delta 4-steroid 5 beta-reductase deficiency. Acta Paediatr Jpn. 1998 Jun;40(3):211-7. [PubMed:9695292 ]
- Magera MJ, Gunawardena ND, Hahn SH, Tortorelli S, Mitchell GA, Goodman SI, Rinaldo P, Matern D: Quantitative determination of succinylacetone in dried blood spots for newborn screening of tyrosinemia type I. Mol Genet Metab. 2006 May;88(1):16-21. Epub 2006 Jan 31. [PubMed:16448836 ]
- Endo F, Katoh H, Yamamoto S, Matsuda I: A murine model for type III tyrosinemia: lack of immunologically detectable 4-hydroxyphenylpyruvic acid dioxygenase enzyme protein in a novel mouse strain with hypertyrosinemia. Am J Hum Genet. 1991 Apr;48(4):704-9. [PubMed:2014797 ]
- Cassiman D, Zeevaert R, Holme E, Kvittingen EA, Jaeken J: A novel mutation causing mild, atypical fumarylacetoacetase deficiency (Tyrosinemia type I): a case report. Orphanet J Rare Dis. 2009 Dec 15;4:28. doi: 10.1186/1750-1172-4-28. [PubMed:20003495 ]
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