Summary: Salts and esters of the 7-carbon saturated monocarboxylic acid heptanoic acid.

Top Publications

  1. Schulze A, Frommhold D, Hoffmann G, Mayatepek E. Spectrophotometric microassay for delta-aminolevulinate dehydratase in dried-blood spots as confirmation for hereditary tyrosinemia type I. Clin Chem. 2001;47:1424-9 pubmed
    ..We developed a semiquantitative assay based on inhibition of delta-aminolevulinate dehydratase (ALA-D) by succinylacetone...
  2. Erskine P, Newbold R, Brindley A, Wood S, Shoolingin Jordan P, Warren M, et al. The x-ray structure of yeast 5-aminolaevulinic acid dehydratase complexed with substrate and three inhibitors. J Mol Biol. 2001;312:133-41 pubmed
    ..It appears that we have defined the structure of an intermediate of Schiff base formation that the substrate forms upon binding to the P-site of the enzyme. ..
  3. Weigel J, Janzen N, Pfaffle R, Thiery J, Kiess W, Ceglarek U. Tandem mass spectrometric determination of succinylacetone in dried blood spots enables presymptomatic detection in a case of hepatorenal tyrosinaemia. J Inherit Metab Dis. 2007;30:610 pubmed
    ..This indicates that identification of all newborns with hepatorenal tyrosinaemia is only possible by determination of succinylacetone as part of the newborn screening process...
  4. Deng S, Zhang G, Kasumov T, Roe C, Brunengraber H. Interrelations between C4 ketogenesis, C5 ketogenesis, and anaplerosis in the perfused rat liver. J Biol Chem. 2009;284:27799-807 pubmed publisher
    ..Anaplerosis and gluconeogenesis from heptanoate are inhibited by octanoate. The data have implications for the design of diets for the treatment of long chain fatty acid oxidation disorders, such as the triheptanoin-based diet. ..
  5. Han L, Ye J, Qiu W, Zhang H, Wang Y, Ji W, et al. [Application of succinylacetone levels measurement in the blood and urine in the diagnosis of tyrosinemia type 1]. Zhonghua Er Ke Za Zhi. 2012;50:126-30 pubmed
  6. Nakagawa N, Yuhki K, Kawabe J, Fujino T, Takahata O, Kabara M, et al. The intrinsic prostaglandin E2-EP4 system of the renal tubular epithelium limits the development of tubulointerstitial fibrosis in mice. Kidney Int. 2012;82:158-71 pubmed publisher
    ..Hence, an endogenous PGE(2)-EP(4) system in the tubular epithelium limits the development of tubulointerstitial fibrosis by suppressing inflammatory responses. ..
  7. Bourdon E, Kang D, Ghosh M, Drake S, Wey J, Levine R, et al. The role of endogenous heme synthesis and degradation domain cysteines in cellular iron-dependent degradation of IRP2. Blood Cells Mol Dis. 2003;31:247-55 pubmed
    ..Thus, we could not discern a role for the recently defined in vitro cysteine-dependent iron-binding site of IRP2 in cellular physiology. The early molecular events in iron-dependent degradation of IRP2 remain to be elucidated. ..
  8. Ohta C, Kuwabe S, Shiraishi T, Shinohara I, Araki H, Sakuyama S, et al. An improved synthesis of the selective EP4 receptor agonist ONO-4819. J Org Chem. 2009;74:8298-308 pubmed publisher
    ..By changing these protecting groups, the purity of ONO-4819 was strictly controlled through crystalline intermediates. Thus, an improved robust process for ONO-4819 with a high chemical purity was developed. ..
  9. Zhu Y, Lee H, Zhang L. An examination of heme action in gene expression: heme and heme deficiency affect the expression of diverse genes in erythroid k562 and neuronal PC12 cells. DNA Cell Biol. 2002;21:333-46 pubmed
    ..These studies provide insights into how heme may act to control diverse regulatory processes in mammals. ..

More Information


  1. Zhu Y, Hon T, Ye W, Zhang L. Heme deficiency interferes with the Ras-mitogen-activated protein kinase signaling pathway and expression of a subset of neuronal genes. Cell Growth Differ. 2002;13:431-9 pubmed
    ..Our data provide insights into how heme deficiency interferes with NGF signaling and abrogates programs of neuronal gene expression, thus ultimately causing defective neuronal functions. ..
  2. Adam B, Lim T, Hall E, Hannon W. Preliminary proficiency testing results for succinylacetone in dried blood spots for newborn screening for tyrosinemia type I. Clin Chem. 2009;55:2207-13 pubmed publisher
    ..Although DBS matrix calibrators are important for optimizing SUAC recoveries, the preparation of these calibrators is not standardized among laboratories. Certified DBS-based SUAC calibrators are needed for accuracy and harmonization. ..
  3. Dhillon K, Bhandal A, Aznar C, Lorey F, Neogi P. Improved tandem mass spectrometry (MS/MS) derivatized method for the detection of tyrosinemia type I, amino acids and acylcarnitine disorders using a single extraction process. Clin Chim Acta. 2011;412:873-9 pubmed publisher
    ..The concentration of hydrazine had considerable impact on SUAC extraction. We developed a new MS/MS derivatized method to detect AA/AC/SUAC in a single extraction process for screening Tyr I along with disorders of AA and AC. ..
  4. Jones P, Butt Y, Bennett M. Effects of odd-numbered medium-chain fatty acids on the accumulation of long-chain 3-hydroxy-fatty acids in long-chain L-3-hydroxyacyl CoA dehydrogenase and mitochondrial trifunctional protein deficient skin fibroblasts. Mol Genet Metab. 2004;81:96-9 pubmed
    ..We found that provision of odd-chain species does decrease the build-up of long-chain FAO intermediates in our in vitro skin fibroblast model, but to a lesser extent than even-numbered MCFAs. ..
  5. Suenaga A, Fujii T, Ogawa H, Maruyama T, Ohuchida S, Katsube N, et al. Up-regulation of lymphocytic cholinergic activity by ONO-4819, a selective prostaglandin EP4 receptor agonist, in MOLT-3 human leukemic T cells. Vascul Pharmacol. 2004;41:51-8 pubmed
  6. Rafienia M, Emami S, Mirzadeh H, Mobedi H, Karbasi S. Influence of poly (lactide-co-glycolide) type and gamma irradiation on the betamethasone acetate release from the in situ forming systems. Curr Drug Deliv. 2009;6:184-91 pubmed
    ..5-41%) than the samples based on RG504H (60-67%) and mixture of them (30-33%). Regarding this research three different kinds of steriled in situ forming systems were developed which can release BTMA for 24, 90 and 60 days. ..
  7. Al Dirbashi O, Jacob M, Al Ahaidib L, Al Qahtani K, Rahbeeni Z, Al Owain M, et al. Quantification of succinylacetone in urine of hepatorenal tyrosinemia patients by HPLC with fluorescence detection. Clin Chim Acta. 2006;365:243-8 pubmed
    ..The method requires a minimal sample volume (0.1 ml) with simple instrumentation. The method enabled us to differentiate HT1 cases (n=14) from controls (n=104), regardless of the years of urine storage. ..
  8. Okere I, McElfresh T, Brunengraber D, Martini W, Sterk J, Huang H, et al. Differential effects of heptanoate and hexanoate on myocardial citric acid cycle intermediates following ischemia-reperfusion. J Appl Physiol (1985). 2006;100:76-82 pubmed
    ..This suggests that reduced anaplerosis and CAC dysfunction do not play a major role in contractile and metabolic derangements observed with a 60% decrease in coronary flow followed by reperfusion. ..
  9. Kolluri S, Sadlon T, May B, Bonkovsky H. Haem repression of the housekeeping 5-aminolaevulinic acid synthase gene in the hepatoma cell line LMH. Biochem J. 2005;392:173-80 pubmed
  10. Kolluri S, Elbirt K, Bonkovsky H. Heme biosynthesis in a chicken hepatoma cell line (LMH): comparison with primary chick embryo liver cells (CELC). Biochim Biophys Acta. 1999;1472:658-67 pubmed
    ..Similarly, heme repressed ALA synthase mRNA levels in both cell types and ALA synthase activities in LMH cells. We conclude that LMH cells are a useful model for the study of hepatic heme biosynthesis and regulation of ALA synthase. ..
  11. Kajino H, Taniguchi T, Fujieda K, Ushikubi F, Muramatsu I. An EP4 receptor agonist prevents indomethacin-induced closure of rat ductus arteriosus in vivo. Pediatr Res. 2004;56:586-90 pubmed
    ..These results suggest that administration of an EP4 agonist in addition to indomethacin might prevent adverse reactions of indomethacin on fetal DA without restricting its tocolytic effects. ..
  12. Hagino H, Kuraoka M, Kameyama Y, Okano T, Teshima R. Effect of a selective agonist for prostaglandin E receptor subtype EP4 (ONO-4819) on the cortical bone response to mechanical loading. Bone. 2005;36:444-53 pubmed
    ..05, BFR/BS P < 0.03, for ONO-4819 all P < 0.001). It was concluded that ONO-4819 increased cortical bone formation in rats and there was an additive effect on the bone response to external loading by 4-point bending. ..
  13. Bondanelli M, Ambrosio M, Margutti A, Franceschetti P, Zatelli M, degli Uberti E. Activation of the somatotropic axis by testosterone in adult men: evidence for a role of hypothalamic growth hormone-releasing hormone. Neuroendocrinology. 2003;77:380-7 pubmed
    ..These findings are consistent with the view that in humans the stimulatory action of T on the GH axis appears to be mediated at the hypothalamic level primarily by promoting GHRH function. ..
  14. Shih S, Yang H, Jebrail M, Fobel R, McIntosh N, Al Dirbashi O, et al. Dried blood spot analysis by digital microfluidics coupled to nanoelectrospray ionization mass spectrometry. Anal Chem. 2012;84:3731-8 pubmed publisher
    ..We propose that the new methods described here can potentially contribute to a new generation of analytical techniques for quantifying analytes in DBS samples for a wide range of applications. ..
  15. Pierik L, van Spronsen F, Bijleveld C, van Dael C. Renal function in tyrosinaemia type I after liver transplantation: a long-term follow-up. J Inherit Metab Dis. 2005;28:871-6 pubmed
    ..Progressive tubular dysfunction can cause glomerular damage. The use of low-dose NTBC might be considered after liver transplantation in case of tubulopathy to prevent progression of tubular and glomerular dysfunction. ..
  16. Peng M, Liu L, Peng L. Evaluation of factors influencing accuracy in the analysis of succinylacetone in dried blood spots. Clin Chim Acta. 2012;413:1265-9 pubmed publisher
  17. Dhanasekaran S, Chandra N, Chandrasekhar Sagar B, Rangarajan P, Padmanaban G. Delta-aminolevulinic acid dehydratase from Plasmodium falciparum: indigenous versus imported. J Biol Chem. 2004;279:6934-42 pubmed
    ..It is proposed that the role of PfALAD may be confined to heme synthesis in the apicoplast that may not account for the total de novo heme biosynthesis in the parasite. ..
  18. Al Dirbashi O, Rashed M, Jacob M, Al Ahaideb L, Al Amoudi M, Rahbeeni Z, et al. Improved method to determine succinylacetone in dried blood spots for diagnosis of tyrosinemia type 1 using UPLC-MS/MS. Biomed Chromatogr. 2008;22:1181-5 pubmed publisher
    ..63 micromol/L (n = 151). In dried blood spots from patients with established tyrosinemia type 1 (n = 11), concentration of succinylacetone was 6.4-30.8 micromol/L...
  19. Marin Valencia I, Good L, Ma Q, Malloy C, Pascual J. Heptanoate as a neural fuel: energetic and neurotransmitter precursors in normal and glucose transporter I-deficient (G1D) brain. J Cereb Blood Flow Metab. 2013;33:175-82 pubmed publisher
    ..These results enlighten the mechanism of heptanoate metabolism in the normal and glucose-deficient brain and encourage further studies to elucidate its potential antiepileptic effects in disorders of energy metabolism. ..
  20. Sander J, Janzen N, Peter M, Sander S, Steuerwald U, Holtkamp U, et al. Newborn screening for hepatorenal tyrosinemia: Tandem mass spectrometric quantification of succinylacetone. Clin Chem. 2006;52:482-7 pubmed
    ..We present our experience with a newly described method for succinylacetone quantification in routine newborn screening...
  21. Sasaoka R, Terai H, Toyoda H, Imai Y, Sugama R, Takaoka K. A prostanoid receptor EP4 agonist enhances ectopic bone formation induced by recombinant human bone morphogenetic protein-2. Biochem Biophys Res Commun. 2004;318:704-9 pubmed
  22. Yang L, Huang Y, Porta R, Yanagisawa K, Gonzalez A, Segi E, et al. Host and direct antitumor effects and profound reduction in tumor metastasis with selective EP4 receptor antagonism. Cancer Res. 2006;66:9665-72 pubmed
    ..Selective antagonism of the EP4 receptor may thus represent a novel therapeutic approach for the treatment of cancer and especially its propensity to metastasize. ..
  23. Adam B, Hall E, Meredith N, Lim T, Haynes C, De Jesus V, et al. Performance of succinylacetone assays and their associated proficiency testing outcomes. Clin Biochem. 2012;45:1658-63 pubmed publisher
    ..Method-related differences in SUAC concentrations of tyrosinemia patients' samples were consistent with those of PT specimens. ..
  24. Magera M, Gunawardena N, Hahn S, Tortorelli S, Mitchell G, Goodman S, et al. Quantitative determination of succinylacetone in dried blood spots for newborn screening of tyrosinemia type I. Mol Genet Metab. 2006;88:16-21 pubmed
    ..This assay has the potential to significantly reduce the number of false positive results in newborn screening for TYR 1 and can also be used for the laboratory follow up of patients treated for TYR 1. ..
  25. Fiume M, Bergfeld W, Belsito D, Hill R, Klaassen C, LIEBLER D, et al. Safety assessment of stearyl heptanoate and related stearyl alkanoates as used in cosmetics. Int J Toxicol. 2012;31:141S-6S pubmed publisher
    ..The Expert Panel concluded that stearyl heptanoate, stearyl caprylate, stearyl palmitate, stearyl stearate, stearyl behenate, and stearyl olivate are safe in the present practices of use and concentration. ..
  26. Sakaino M, Kataoka T, Taketani S. Post-transcriptional regulation of the expression of ferrochelatase by its variant mRNA. J Biochem. 2009;145:733-8 pubmed publisher
    ..These results demonstrated the haem-dependent negative feedback regulation of the expression of FECH at a post-transcriptional level. ..
  27. Royer L, Knudsen F, de Oliveira M, Tavares M, Bechara E. Succinylacetone oxidation by oxygen/peroxynitrite: a possible source of reactive intermediates in hereditary tyrosinemia type I. Chem Res Toxicol. 2004;17:598-604 pubmed
    ..The results obtained may help shed light on the role of both SA and oxidative stress in the pathogenesis of HT1. ..
  28. Rashed M, Al Ahaidib L, Al Dirbashi O, Al Amoudi M, Al Sayed M, Rahbeeni Z, et al. Tandem mass spectrometric assay of succinylacetone in urine for the diagnosis of hepatorenal tyrosinemia. Anal Biochem. 2005;339:310-7 pubmed
    ..During the course of this study, we identified 12 new patients with HT1 and applied this method to follow up the treatment of 4 of these patients as well as previously diagnosed HT1 patients. ..
  29. la Marca G, Malvagia S, Pasquini E, Innocenti M, Fernandez M, Donati M, et al. The inclusion of succinylacetone as marker for tyrosinemia type I in expanded newborn screening programs. Rapid Commun Mass Spectrom. 2008;22:812-8 pubmed publisher
    ..Including succinylacetone in newborn screening programs for amino acids and acylcarnitines avoids false-negative results for tyrosinemia type I. Newborn screening laboratories should consider implementing these modifications. ..
  30. Zitzmann M, Junker R, Kamischke A, Nieschlag E. Contraceptive steroids influence the hemostatic activation state in healthy men. J Androl. 2002;23:503-11 pubmed
    ..Down-regulation of the hemostatic system with testosterone alone may indicate an antithrombotic effect, whereas clinical consequences of an additional gestagen compound cannot be derived. ..
  31. Roe C, Mochel F. Anaplerotic diet therapy in inherited metabolic disease: therapeutic potential. J Inherit Metab Dis. 2006;29:332-40 pubmed
  32. Cable E, Greene Y, Healey J, Evans C, Bonkovsky H. Mechanism of synergistic induction of hepatic heme oxygenase by glutethimide and iron: studies in cultured chick embryo liver cells. Biochem Biophys Res Commun. 1990;168:176-81 pubmed
    ..Glutethimide and iron appeared to induce at the transcriptional level since both heme oxygenase mRNA and protein levels correlate with changes in heme oxygenase activity. ..
  33. Pass K, Morrissey M. Enhancing newborn screening for tyrosinemia type I. Clin Chem. 2008;54:627-9 pubmed publisher
  34. Honma Y, Arai I, Hashimoto Y, Futaki N, Sugimoto M, Tanaka M, et al. Prostaglandin D2 and prostaglandin E2 accelerate the recovery of cutaneous barrier disruption induced by mechanical scratching in mice. Eur J Pharmacol. 2005;518:56-62 pubmed
    ..These results suggest that prostaglandin D2 and prostaglandin E2 accelerate the recovery process of cutaneous barrier disruption caused by mechanical scratching, via specific prostanoid DP1, EP3 and EP4 receptors. ..
  35. Zheng K, Yalowich J, Kagan V, Keohavong P. Increased mutant frequencies in the HPRT gene locus of leukemia HL-60 cells treated with succinylacetone. Cell Biol Toxicol. 2006;22:361-70 pubmed
  36. Van Dyk E, Steenkamp A, Koekemoer G, Pretorius P. Hereditary tyrosinemia type 1 metabolites impair DNA excision repair pathways. Biochem Biophys Res Commun. 2010;401:32-6 pubmed publisher
    ..Our results indicate that the metabolites affected the repair mechanisms differently, since the metabolites had a bigger detrimental effect on BER than on NER. ..
  37. Nussinovitch M, Campino G, Shapira R, Voluvitz B, Amir J. [Liver failure with coagulopathy in an infant with tyrosinemia]. Harefuah. 2001;140:578-9, 680 pubmed
  38. Cansever M, Erim F. Determination of urinary succinylacetone by capillary electrophoresis for the diagnosis of tyrosinemia type I. J Chromatogr B Analyt Technol Biomed Life Sci. 2005;818:309-11 pubmed
    ..For all patients, diagnostic peaks at the expected migration times were detected. The developed method is rapid, simple, inexpensive, and suitable for the determination of succinylacetone in clinical urine samples. ..
  39. Shanmugam D, Wu B, Ramirez U, Jaffe E, Roos D. Plastid-associated porphobilinogen synthase from Toxoplasma gondii: kinetic and structural properties validate therapeutic potential. J Biol Chem. 2010;285:22122-31 pubmed publisher
    ..The distinct phylogenetic, enzymatic, and structural features of apicomplexan PBGS offer scope for developing selective inhibitors of the parasite enzyme based on its quaternary structure characteristics. ..
  40. Park H, Lee D, Choi T, Lee Y, Kim J, Ki C, et al. Clinical, biochemical, and genetic analysis of a Korean neonate with hereditary tyrosinemia type 1. Clin Chem Lab Med. 2009;47:930-3 pubmed publisher
    ..The patient's parents were not consanguineous but were heterozygous carriers of the same mutation. The patient had a novel, large deletion mutation of FAH and is the first report of genetically confirmed HT1 in Korea. ..
  41. Tahara T, Sun J, Igarashi K, Taketani S. Heme-dependent up-regulation of the alpha-globin gene expression by transcriptional repressor Bach1 in erythroid cells. Biochem Biophys Res Commun. 2004;324:77-85 pubmed
    ..These results indicated that heme plays an important role in the induction of alpha-globin gene expression through disrupting the interaction of Bach1 and the NA site in HS-40 enhancer in erythroid cells. ..
  42. Metz T, Mechtler T, Merk M, Gottschalk A, Lukacin R, Herkner K, et al. Evaluation of a novel, commercially available mass spectrometry kit for newborn screening including succinylacetone without hydrazine. Clin Chim Acta. 2012;413:1259-64 pubmed publisher
    ..The novel assay was demonstrated to be accurate in the detection of newborns with IEM, robust, and above all, without the risk of the exposure to highly toxic reagents and requirement of additional equipment for toxic fume evacuation...
  43. Bal D, Kraska Dziadecka A, Gryff Keller A. Solution structure of succinylacetone, an unsymmetrical beta-diketone, as studied by 13C NMR and GIAO-DFT calculations. J Org Chem. 2009;74:8604-9 pubmed publisher
  44. Turgeon C, Magera M, Allard P, Tortorelli S, Gavrilov D, Oglesbee D, et al. Combined newborn screening for succinylacetone, amino acids, and acylcarnitines in dried blood spots. Clin Chem. 2008;54:657-64 pubmed publisher
    ..25 micromol/L. The inclusion of SUAC analysis into routine analysis of AC and AA allows for rapid and cost-effective screening for TYR 1 with no tangible risk of false-negative results. ..
  45. Rong J, Nelson M, Kusche B, Priestley N. Nonactin biosynthesis: unexpected patterns of label incorporation from 4,6-dioxoheptanoate show evidence of a degradation pathway for levulinate through propionate in Streptomyces griseus. J Nat Prod. 2010;73:2009-12 pubmed publisher
    ..griseus. ..
  46. Grootscholten T, Steinbusch K, Hamelers H, Buisman C. High rate heptanoate production from propionate and ethanol using chain elongation. Bioresour Technol. 2013;136:715-8 pubmed publisher
    ..2 g l(-1). These results show sufficient potential to consider this approach as an alternative for heptanoate production from castor oil. Future research should make heptanoate production from propionate and ethanol more cost-effective. ..
  47. Beauloye C, Horman S, Bertrand L. Even is better than odd: one fat may conceal another. Am J Physiol Heart Circ Physiol. 2015;309:H1112-4 pubmed publisher
  48. Schlump J, Mayatepek E, Spiekerkoetter U. Significant increase of succinylacetone within the first 12 h of life in hereditary tyrosinemia type 1. Eur J Pediatr. 2010;169:569-72 pubmed publisher
    ..In most countries, hereditary tyrosinemia type 1 is not included in routine newborn screening...
  49. Cassiman D, Zeevaert R, Holme E, Kvittingen E, Jaeken J. A novel mutation causing mild, atypical fumarylacetoacetase deficiency (Tyrosinemia type I): a case report. Orphanet J Rare Dis. 2009;4:28 pubmed publisher
    ..This is the first report of mild tyrosinemia type I disease caused by an Ala35Thr mutation in the FAH gene, presenting atypically without increase of the diagnostically important toxic metabolites succinylacetone and succinylacetoacetate...
  50. Bourque S, Benjamin C, Adams M, Nakatsu K. Lack of hemodynamic effects after extended heme synthesis inhibition by succinylacetone in rats. J Pharmacol Exp Ther. 2010;333:290-6 pubmed publisher
    ..The present results demonstrate that extended inhibition of heme synthesis with SA affects hemoenzyme function, albeit without consequent effects on BP regulation and sodium excretion. ..
  51. Dou L, Fang L, Wang X, Lu W, Chen R, Li L, et al. [Mutation analysis of FAH gene in patients with tyrosinemia type 1]. Zhonghua Er Ke Za Zhi. 2013;51:302-7 pubmed
    ..Mutations c.455G > A and c.1027G > A can be detected in FAH gene of Chinese children. ..
  52. Gu L, Zhang G, Kombu R, Allen F, Kutz G, Brewer W, et al. Parenteral and enteral metabolism of anaplerotic triheptanoin in normal rats. II. Effects on lipolysis, glucose production, and liver acyl-CoA profile. Am J Physiol Endocrinol Metab. 2010;298:E362-71 pubmed publisher
    ..Our data suggest that triheptanoin, administered either intravenously or intraduodenally, could be used for intensive care and nutritional support of metabolically decompensated long-chain fatty acid oxidation disorders. ..
  53. Stinton C, Geppert J, Freeman K, Clarke A, Johnson S, Fraser H, et al. Newborn screening for Tyrosinemia type 1 using succinylacetone - a systematic review of test accuracy. Orphanet J Rare Dis. 2017;12:48 pubmed publisher
    ..Confirmation of test accuracy data should be obtained from studies that include a two-year follow-up of individuals who screen negative. ..