L-α-Hydroxyglutaric Acid |
| (Synonyms: 2(S)-HG, 2(S)-Hydroxyglutaric Acid, L-2-HG, L-2-Hydroxyglutaric Acid) Catalog No.: GC41478 |
L-α-Hydroxyglutaric Acid is an important metabolite in various domains of life.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.:13095-48-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
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Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
CD8-positive T-lymphocytes |
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Preparation Method |
Cells were activated with anti-CD3 and anti-CD28 antibodies for 48 h, then expanded for an additional 4 days in the presence of IL-2 and then treated with the indicated concentration of L-α-Hydroxyglutaric Acid for 16 h. |
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Reaction Conditions |
300,500 μM L-α-Hydroxyglutaric Acid for 16 h |
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Applications |
L-α-Hydroxyglutaric Acid inhibited the production of effector cytokines and reduced cytotoxicity. In addition, when the dose of L-α-Hydroxyglutaric Acid was more than 300 μM, L-α-Hydroxyglutaric Acid inhibited cell expansion, increased cell apoptosis, decreased IFN-γ secretion, but increased IL-2 secretion. |
| Animal experiment [2]: | |
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Animal models |
Wistar rats |
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Preparation Method |
The homogenates of different mouse tissues were mixed with the corresponding buffer, and L-α-Hydroxyglutaric Acid at a final concentration of 0.25 to 5 mM was also added to the medium. |
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Dosage form |
0.25 to 5 mM L-α-Hydroxyglutaric Acid for 15 min at 37 °C |
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Applications |
When examined the effect of L-α-Hydroxyglutaric Acid, at concentrations varying from 1 to 5 mM, on CK activity in total homogenates from cerebellum, cerebral cortex, skeletal muscle and cardiac muscle. L-α-Hydroxyglutaric Acid did not alter tCK activities from cerebral cortex, skeletal muscle, and cardiac muscle, but significantly inhibited the enzyme activity from cerebellum at all concentrations tested. |
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References: [1]. Tyrakis PA, Palazon A, et,al. S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate. Nature. 2016 Dec 8;540(7632):236-241. doi: 10.1038/nature20165. Epub 2016 Oct 26. PMID: 27798602; PMCID: PMC5149074. [2]. da Silva CG, Bueno AR, et,al. L-2-hydroxyglutaric acid inhibits mitochondrial creatine kinase activity from cerebellum of developing rats. Int J Dev Neurosci. 2003 Jun;21(4):217-24. doi: 10.1016/s0736-5748(03)00035-2. PMID: 12781789. |
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L-α-Hydroxyglutaric Acid is an important metabolite in various domains of life. In mammals and plants, it is produced by lactate dehydrogenase (LDH) and malate dehydrogenase (MDH)-mediated 2-ketoglutarate (2-KG) reduction under hypoxic conditions[2]. L-α-Hydroxyglutaric Acid is an inhibitor of 2-KG dependent dioxygenases with specific pro-oncogenic capabilities[3,4].
In CD8-positive T-lymphocytes, L-α-Hydroxyglutaric Acid inhibited the production of effector cytokines and reduced cytotoxicity. In addition, when the dose of L-α-Hydroxyglutaric Acid was more than 300 μM, L-α-Hydroxyglutaric Acid inhibited cell expansion, increased cell apoptosis, decreased IFN-γ secretion, but increased IL-2 secretion[6].This compound was identified to aid the proliferation and antitumorigenic abilities of CD8+ T-lymphocytes, to contribute to relieving the cellular reductive stress[5].
When examined the effect of L-α-Hydroxyglutaric Acid, at concentrations varying from 1 to 5 mM, on CK activity in total homogenates from cerebellum, cerebral cortex, skeletal muscle and cardiac muscle. L-α-Hydroxyglutaric Acid did not alter tCK activities from cerebral cortex, skeletal muscle, and cardiac muscle, but significantly inhibited the enzyme activity from cerebellum at all concentrations tested. The inhibition of Mi-CK activity by L-α-Hydroxyglutaric Acid is non-competitive. The Km calculated was 2.52±0.74 mM. The Ki value was calculated by the method of which provides a simple way of determining the inhibition constant (Ki) for non-competitive inhibitors. The Ki value calculated was 11.13±3.71 mM for L-α-Hydroxyglutaric Acid [1].
Besides, in Zebrafish, L-α-Hydroxyglutaric Acid-induced apoptosis was caused by oxidation[7].
References:
[1]: da Silva CG, Bueno AR, et,al. L-2-hydroxyglutaric acid inhibits mitochondrial creatine kinase activity from cerebellum of developing rats. Int J Dev Neurosci. 2003 Jun;21(4):217-24. doi: 10.1016/s0736-5748(03)00035-2. PMID: 12781789.
[2]: Oldham WM, Clish CB, et,al. Hypoxia-Mediated Increases in L-2-hydroxyglutarate Coordinate the Metabolic Response to Reductive Stress. Cell Metab. 2015 Aug 4;22(2):291-303. doi: 10.1016/j.cmet.2015.06.021. Epub 2015 Jul 23. PMID: 26212716; PMCID: PMC4526408.
[3]: Xu W, Yang H, et,al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell. 2011 Jan 18;19(1):17-30. doi: 10.1016/j.ccr.2010.12.014. PMID: 21251613; PMCID: PMC3229304.
[4]: Chowdhury R, Yeoh KK, et,al. The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases. EMBO Rep. 2011 May;12(5):463-9. doi: 10.1038/embor.2011.43. Epub 2011 Apr 1. PMID: 21460794; PMCID: PMC3090014.
[5]: Tyrakis PA, Palazon A, et,al. S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate. Nature. 2016 Dec 8;540(7632):236-241. doi: 10.1038/nature20165. Epub 2016 Oct 26. PMID: 27798602; PMCID: PMC5149074.
[6]: Tyrakis PA, Palazon A, et,al. S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate. Nature. 2016 Dec 8;540(7632):236-241. doi: 10.1038/nature20165. Epub 2016 Oct 26. PMID: 27798602; PMCID: PMC5149074.
[7]:Parng C, Ton C, et,al. A zebrafish assay for identifying neuroprotectants in vivo. Neurotoxicol Teratol. 2006 Jul-Aug;28(4):509-16. doi: 10.1016/j.ntt.2006.04.003. Epub 2006 Jun 30. PMID: 16814516.
| Cas No. | 13095-48-2 | SDF | |
| Synonyms | 2(S)-HG, 2(S)-Hydroxyglutaric Acid, L-2-HG, L-2-Hydroxyglutaric Acid | ||
| Chemical Name | 2S-hydroxy-pentanedioic acid | ||
| Canonical SMILES | OC(CC[C@H](O)C(O)=O)=O | ||
| Formula | C5H8O5 | M.Wt | 148.1 |
| Solubility | 10mg/mL in PBS, pH 7.2 | Storage | Store at -20°C |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
| Shipping Condition | Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request |
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Enantioseparation of d,l-2-hydroxyglutaric acid by capillary electrophoresis with tandem mass spectrometry-Fast and efficient tool for d- and l-2-hydroxyglutaracidurias diagnosis
J Chromatogr A2016 Oct 7;1467:383-390.PMID: 27295961DOI: 10.1016/j.chroma.2016.05.095
A novel capillary electrophoresis-tandem mass spectrometry method for the enantioseparation and identification of 2-hydroxyglutaric acid enantiomers without derivatization for clinical purposes was described. Vancomycin chloride was used as an efficient chiral selector for the discrimination of 2-hydroxyglutaric acid enantiomers by capillary electrophoresis employed complete capillary filling method. The obtained resolution was 2.05. Hyphenation of CE with tandem mass spectrometry allows a reliable identification of separated enantiomers as well as their quantification. The method was validated and applied for the separation, identification and determination of 2-hydroxyglutaric enantiomers in urine samples obtained from healthy patients and two urine samples obtained from child patients suffering from high urine excretion of 2-hydroxyglutaric acid. Abnormal excretion of d-hydroxyglutaric acid was found in both child urine samples (104.5±2.1 and 2200.0±12.6mmol/mol of creatinine, respectively). The limits of detection for d- and L-Hydroxyglutaric Acid were 31 and 38nmol/L, respectively.
A zebrafish assay for identifying neuroprotectants in vivo
Neurotoxicol Teratol2006 Jul-Aug;28(4):509-16.PMID: 16814516DOI: 10.1016/j.ntt.2006.04.003
In this study, we developed an in vivo method to determine drug effects on oxidation-induced apoptosis in the zebrafish brain caused by treatment with L-Hydroxyglutaric Acid (LGA). We confirmed that LGA-induced apoptosis was caused by oxidation by examining the presence of an oxidative product, nitrotyrosine. Next, we examined the effects of 14 characterized neuroprotectants on LGA-treated zebrafish, including: D-methionine (D-Met), Indole-3-carbinol, deferoxamine (DFO), dihydroxybenzoate (DHB), deprenyl, L-NAME (N(G)-nitro-L-arginine methyl ester), n-acetyl L-cysteine (L-NAC), 2-oxothiazolidine-4-carboxylate (OTC), lipoic acid, minocycline, isatin, cortisone, ascorbic acid and alpha-tocopherol. Eleven of 14 neuroprotectants and 7 of 7 synthetic anti-oxidants exhibit significant protection in zebrafish. Buthionine sulfoximine (BSO), used as a negative control, exhibited no significant protective effects. In addition, three blood-brain barrier (BBB) impermeable compounds exhibited no significant effects. Our results in zebrafish were similar to results reported in mammals supporting the utility of this in vivo method for identifying potential neuroprotective anti-oxidants.
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