4,6-Dioxoheptanoic acid
(Synonyms: 4,6-二氧代庚酸) 目录号 : GC32483
An inhibitor of δ-aminolevulinic acid dehydratase
Cas No.:51568-18-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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)
| Cas No. | 51568-18-4 | SDF | |
| 别名 | 4,6-二氧代庚酸 | ||
| Canonical SMILES | CC(=O)CC(=O)CCC(O)=O | ||
| 分子式 | C7H10O4 | 分子量 | 158.15 |
| 溶解度 | DMSO : 100 mg/mL (632.31 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 6.3231 mL | 31.6156 mL | 63.2311 mL |
| 5 mM | 1.2646 mL | 6.3231 mL | 12.6462 mL |
| 10 mM | 0.6323 mL | 3.1616 mL | 6.3231 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Identification of 4,6-Dioxoheptanoic acid (succinylacetone), 3,5-dioxooctanedioic acid (succinylacetoacetate) and 4-Oxo-6-hydroxyheptanoic acid in the urine from patients with hereditary tyrosinemia
Biomed Mass Spectrom 1982 Oct;9(10):419-24.PMID:7171740DOI:10.1002/bms.1200091003.
In the urine from patients with hereditary tyrosinemia, three characteristic compounds have been found. They have been identified as 4,6-Dioxoheptanoic acid (succinylacetone), 3,5-dioxooctanedioic acid (succinyl-acetoacetate) and 4-oxo-6-hydroxyheptanoic acid. The identities have been established by mass spectrometry of several derivatives, and by comparison with a synthetic sample of 4,6-Dioxoheptanoic acid.
The effects of levulinic Acid and 4,6-Dioxoheptanoic acid on the metabolism of etiolated and greening barley leaves
Plant Physiol 1981 Apr;67(4):728-32.PMID:16661744DOI:10.1104/pp.67.4.728.
Application of levulinic acid (LA), a competitive inhibitor of delta-aminolevulinic acid (ALA) dehydratase, to greening plant tissues causes ALA to accumulate at the expense of chlorophyll. 4,6-Dioxoheptanoic acid (DA), which has been reported to be an effective inhibitor of this enzyme in animal systems, has a similar but more powerful effect on ALA and chlorophyll metabolism in greening leaves of Hordeum vulgare L. var. Larker. Both LA and DA also inhibit the uptake of [(14)C]amino acids into etiolated and greening barley leaves and reduce their incorporation into protein. Treatment of etiolated and greening leaves with these compounds results in the inhibition of (14)CO(2) evolution from labeled precursors, including amino and organic acids. Inhibition of (14)CO(2) evolution by these compounds is more effective in greening leaves than in etiolated leaves when [4-(14)C]ALA or [1-(14)C]glutamate are employed as precursors. Both LA and DA also inhibit the uptake and increase the incorporation of (32)Pi into organophosphorus by etiolated barley leaves. These results indicate that LA and DA have more far-reaching effects upon plant metabolism than was previously believed.
The effects of succinylacetone (4,6-Dioxoheptanoic acid) on delta-aminolevulinate synthase activity and the content of heme in monolayers of chick embryo liver cells
Biochim Biophys Acta 1982 Dec 30;721(4):408-17.PMID:7159602DOI:10.1016/0167-4889(82)90096-9.
Succinylacetone was shown to inhibit aminolevulinate dehydratase (5-aminolevulinate hydro-lyase (adding 5-aminolevulinate and cyclizing), EC 4.2.1.24) to reduce cellular heme and porphyrins and to induce delta-aminolevulinate synthase (succinyl-CoA:glycine C-succinyltransferase (decarboxylating), EC 2.3.1.37) in monolayers of chick embryo liver cells. Marked synergistic effects on delta-aminolevulinate synthase activity were obtained by combining succinylacetone with levulinate and porphyrogenic drugs. The time course of delta-aminolevulinate synthase activity showed a delayed synergistic response.
Studies with 4,6-Dioxoheptanoic acid on etiolated and greening barley leaves
Plant Physiol 1981 Jun;67(6):1065-8.PMID:16661810DOI:10.1104/pp.67.6.1065.
4,6-Dioxoheptanoic acid (DA), an inhibitor of 5-aminolevulinic acid (ALA) dehydratase (EC 4.3.1.24), causes ALA to accumulate at the expense of chlorophyll when applied to greening leaves of Hordeum vulgare L. var. Larker. Preincubating etiolated leaves with DA in darkness eliminates the lag phase in ALA accumulation during a subsequent exposure to illumination. More than 50% of the DA taken up during a 2-hour incubation disappeared during a subsequent 4-hour incubation. These results suggest that barley leaves can metabolize DA, and the products of this metabolism may enhance the capacity for ALA synthesis.
delta-Aminolevulinic Acid Synthase of Euglena gracilis: Regulation of Activity
Plant Physiol 1982 Jul;70(1):219-26.PMID:16662450DOI:10.1104/pp.70.1.219.
delta-Aminolevulinic acid (ALA), a key precursor of the tetrapyrroles heme and chlorophyll, is capable of being synthesized by two different routes in cells of the unicellular green alga Euglena gracilis: from the intact carbon skeleton of glutamate, and via the condensation of glycine and succinyl CoA, mediated by the enzyme ALA synthase. The regulatory properties of ALA synthase were examined in order to establish its role in Euglena.Partially purified Euglena ALA synthase, unlike the case with the bacterial or animal-derived enzyme, does not exhibit allosteric inhibition by the tetrapyrrole pathway products heme, protoporphyrin IX, and porphobilinogen, at concentrations up to 100 micromolar.In aplastidic mutant cells, extractable ALA synthase activity is constant during exponential growth, and decreases to low levels as the cells reach the stationary state. Rapid exponential decline of ALA synthase (t(1/2) = 55 min) occurs after administration of 43 micromolar cycloheximide, but not 6.2 millimolar chloramphenicol. These results suggest that, as in other eukaryotic cells, ALA synthase is synthesized on cytoplasmic ribosomes and is subject to rapid turnover in vivo.Extractable ALA synthase activity increases 2.5-fold within 6 hours after administration of 100 millimolar ethanol, a stimulator of mitochondrial development, and 4.5-fold within 12 hours after administration of 1 millimolar 4,6-Dioxoheptanoic acid, which blocks ALA utilization, suggesting that activity is controlled in vivo by a feedback induction-repression mechanism, coupled with rapid enzyme turnover.In heterotrophically grown wild-type cells, low levels of ALA synthase rapidly increase 4.5-fold within 12 hours after cells are transferred from the light to the dark, and decrease exponentially (t(1/2) = 75 min) when cells are transferred from the dark to light. The dark levels are equal to those in light- or dark-grown aplastidic mutant cells. The low level occurring in light-grown wild-type cells is not altered by the presence of 10 micromolar 3-(3,4-dichlorophenyl)-1,1-dimethylurea, which blocks photosynthetic O(2) production. The decrease that occurs on dark-to-light transfer can be diminished by 12- or 24-hour prior incubation with 6.2 millimolar chloramphenicol, which also retards chlorophyll synthesis after the transfer to light.The positive relationship of ALA synthase activity to degree of mitochondrial expression, and the inverse relationship to plastid development and chlorophyll synthesis, suggests that ALA synthase functions to provide precursors to nonplastid tetrapyrroles in Euglena. In light-grown, wild-type cells, the diminished levels of ALA synthase may be due to the ability of developing plastids to export heme or a heme precursor to other cellular regions, which thereby supplants the necessity for ALA formation via the ALA synthase route.