Succinylacetone

Succinylacetone
Names
	Preferred IUPAC name 4,6-Dioxoheptanoic acid
	Other names Succinyl acetone
Identifiers
CAS Number	51568-18-4 ;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:87897;
ChEMBL	ChEMBL222824;
ChemSpider	5121;
ECHA InfoCard	100.153.292
EC Number	624-726-8;
PubChem CID	5312;
UNII	KZ0KV2Q190 ;
CompTox Dashboard (EPA)	DTXSID50199519 ;
	InChI InChI=1S/C7H10O4/c1-5(8)4-6(9)2-3-7(10)11/h2-4H2,1H3,(H,10,11) Key: WYEPBHZLDUPIOD-UHFFFAOYSA-N;
	SMILES CC(=O)CC(=O)CCC(=O)O;
Properties
Chemical formula	C7H10O4
Molar mass	158.153 g·mol−1
Hazards
	GHS labelling:[1]
Pictograms
Signal word	Warning
Hazard statements	H315, H319, H335
Precautionary statements	P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, P501
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Succinylacetone is a toxic organic compound that arises as an abnormal metabolite in tyrosine catabolism. In normal tyrosine catabolism, fumarylacetoacetate hydrolase converts fumarylacetoacetate to fumarate and acetoacetate. Deficiency of fumarylacetoacetate hydrolase leads to the accumulation of fumarylacetoacetate, which is subsequently converted to succinylacetoacetate. Succinylacetoacetate is then decarboxylated to form succinylacetone.

Patients with tyrosinemia type 1 have a congenital deficiency of fumarylacetoacetate hydrolase, resulting in the accumulation of succinylacetone in blood and urine. Elevated levels of succinylacetone, with or without elevations of tyrosine, are indicative of tyrosinemia type 1. Measurement of succinylacetone is the preferred marker in newborn screening of Tyrosinemia Type 1 due to its high sensitivity and specificity. ^[1] Succinylacetone can also be detected in the urine through LCMS or GCMS.

Succinylacetone also inhibits ALA dehydratase (PBG synthase), an enzyme involved in porphyrin and heme synthesis. This results in increased ALA levels and, in certain patients, precipitates acute neuropathic symptoms, similar to porphyria. Decreased heme concentration can also be seen as a result of this potent inhibition ^[2]

References

^ de Laet C, Dionisi-Vici C, Leonard JV, McKiernan P, Mitchell G, Monti L, et al. (January 2013). "Recommendations for the management of tyrosinaemia type 1". Orphanet Journal of Rare Diseases. 8 8. doi:10.1186/1750-1172-8-8. PMC 3558375. PMID 23311542.
^ Ebert P, Hess R, Frykholm B, Tschudy D (1979). "Succinylacetone, a potent inhibitor of heme biosynthesis: effect on cell growth, heme content and δ-aminolevulinic acid dehydratase activity". Biochemical Pharmacology. 88: 1382–1390. doi:10.1016/0006-291X(79)91133-1.

[de_Laet_2013-1] Laet C, Dionisi-Vici C, Leonard JV, McKiernan P, Mitchell G, Monti L, et al. (January 2013). "Recommendations for the management of tyrosinaemia type 1". Orphanet Journal of Rare Diseases. 8 8. doi:10.1186/1750-1172-8-8. PMC 3558375. PMID 23311542.

[Ebert_1979-2] Ebert P, Hess R, Frykholm B, Tschudy D (1979). "Succinylacetone, a potent inhibitor of heme biosynthesis: effect on cell growth, heme content and δ-aminolevulinic acid dehydratase activity". Biochemical Pharmacology. 88: 1382–1390. doi:10.1016/0006-291X(79)91133-1.

[1]

[2]