Succinylacetone is an inhibitor of δ-aminolevulinic acid dehydratase (Ki = 300 nM for human erythrocyte enzyme).1 It inhibits heme biosynthesis and decreases the growth of murine erythroleukemia cells when used at concentrations of 0.1 and 1 mM.2 Succinylacetone is an abnormal metabolite of tyrosine that accumulates in hereditary tyrosinemia type I, a disorder characterized by a deficiency in fumarylacetoacetate hydrolase (FAH), the final enzyme in tyrosine catabolism.3 Without functional FAH, fumarylacetoacetate is converted into succinylacetone. In a rat model of hypertyrosinemia, succinylacetone (40 mg/kg twice daily) increases levels of δ-aminolevulinic acid in urine, decreases heme levels in liver, kidney, spleen, and vascular tissues, and reduces sensitivity of isolated rat aortic rings to endothelium-dependent and -independent vasodilation. Increased levels of succinylacetone has been used as a marker of tyrosinemia type 1.4
1.Sassa, S., and Kappas, A.Hereditary tyrosinemia and the heme biosynthetic pathway. Profound inhibition of delta-aminolevulinic acid dehydratase activity by succinylacetoneJ. Clin. Invest.71(3)625-634(1983) 2.Ebert, P.S., Hess, R.A., Frykholm, B.C., et al.Succinylacetone, a potent inhibitor of heme biosynthesis: effect on cell growth, heme content and delta-aminolevulinic acid dehydratase activity of malignant murine erythroleukemia cellsbiochem. Biophys. Res. Commun.88(4)1382-1390(1979) 3.Moore, M.E., Koenig, A.E., Hilgartner, M.A., et al.Abnormal social behavior in mice with tyrosinemia type I is associated with an increase of myelin in the cerebral cortexMetab. Brain Dis.32(6)1829-1841(2017) 4.Stinton, C., Geppert, J., Greeman, K., et al.Newborn screening for Tyrosinemia type 1 using succinylacetone - a systematic review of test accuracyOrphanet J. Rare Dis.12(1)48(2017)