63512-50-5

Basic information

• Product Name: L-A-HYDROXYGLUTARIC ACID DISODIUM)
• Synonyms: (S)-2-Hydroxypentanedioic acid;L-α-Hydroxyglutaric acid disodium salt;(2S)-2-Hydroxyglutaric Acid Disodium Salt;s-2-Hydroxypentanedioic acid disodium salt;Pentanedioic acid,2-hydroxy-, disodium salt, (2S)-;(S)-α-Hydroxyglutaric Acid DisodiuM Salt;L-2-Hydroxyglutarate DisodiuM Salt;Pentanedioic acid, 2-hydroxy-, sodiuM salt (1:2)
• CAS NO: 63512-50-5
• Molecular Formula: C₅H₆O₅*2Na
• Molecular Weight: 194.09
• Product Categories: Aliphatics;Chiral Reagents;Inhibitors
• Mol File: 63512-50-5.mol
• Article Data: 2

Chemical Properties

• Melting Point: >300°C
• Appearance: /
• Storage Temp.: −20°C
• Solubility: Methanol (Very Slightly), Water (Slightly)
• BRN: 5318042
• CAS DataBase Reference: L-A-HYDROXYGLUTARIC ACID DISODIUM)(CAS DataBase Reference)
• NIST Chemistry Reference: L-A-HYDROXYGLUTARIC ACID DISODIUM)(63512-50-5)
• EPA Substance Registry System: L-A-HYDROXYGLUTARIC ACID DISODIUM)(63512-50-5)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 63512-50-5(Hazardous Substances Data)

Usage

Description

L-α-Hydroxyglutaric acid (L-2-HG) is an α-hydroxy acid. It is metabolized to 2-oxoglutarate (α-ketoglutarate) by L-2-hydroxyglutarate dehydrogenase, and mutations in this enzyme lead to 2-hydroxyglutaric aciduria, a neurometabolic disorder characterized by increased L-2-HG levels. L-2-HG is structurally similar to α-ketoglutarate and competitively inhibits α-ketoglutarate-dependent dioxygenases, including several involved in histone lysine and DNA demethylation.

Chemical Properties

White Solid

Uses

L-α-Hydroxyglutaric acid disodium salt is suitable for use in collection buffer for increased recovery of hypoxia-inducible factor-1 α (HIF-1α), a marker of hypoxia in human tumors. It is also suitable for the radiolabeled 5mC-5hmC conversion assay to study the effect of 2-HG on the TET family of methyl hydroxylases.

General Description

Glutamic acid is metabolized to α-Hydroxyglutaric acid in an NAD-dependent manner by cell-free extracts of Peptococcus aerogenes. It is formed as an intermediate during glyoxylic acid metabolism in bacteria.

Biochem/physiol Actions

L-alpha-Hydroxyglutaric acid accumulates as a result of a rare defect in L-2-HG dehydogenase, leading to the metabolic disorder L-2-hydroxyglutaric aciduria (L-2HGA). L-2HGA is associated with neuronal defects, leukodystrophy and linked to an increased risk of brain tumors.

in vitro

it has been reported that l-α-hydroxyglutaric acid disodium salt could be used as the collection buffer for increasing the recovery of hypoxia-inducible factor-1 α, which was a marker of hypoxia in human tumors [1]. in another previous study, l-α-hydroxyglutaric acid disodium salt was also used in the radiolabeled conversion assay to evaluate its effect on the tet family of methyl hydroxylases [2].

in vivo

in the 30-day-old rats, l-α-hydroxyglutaric acid was found to be able to significantly increase chemiluminescence, pcf and tba-rs measurements and decrease the tar values in cerebellum markedly. in addition, the l-α-hydroxyglutaric acid-induced increase of tba-rs was significantly attenuated by melatonin and also by the combinations of ascorbic acid and soluble alpha-tocopherol (trolox) and of superoxide dismutase plus catalase but not by the inhibitor of nitric oxide synthase nomega-nitro-l-arginine methyl ester (l-name), , superoxide dismutase or creatine or catalase alone in either cerebral structure [3].

references

[1] park sr,kinders rj,khin s,et al. validation of a hypoxia-inducible factor-1 alpha specimen collection procedure and quantitative enzyme-linked immunosorbent assay in solid tumor tissues. anal biochem.2014 aug 15;459:1-11. [2] evans b,griner e. registered report: oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. elife.2015 jul 31;4:e07420. [3] latini a,scussiato k,rosa rb,leipnitz g,llesuy s,belló-klein a,dutra-filho cs,wajner m. induction of oxidative stress by l-2-hydroxyglutaric acid in rat brain. j neurosci res.2003 oct 1;74(1):103-10.

InChI:InChI=1/C5H8O5.2Na/c6-3(5(9)10)1-2-4(7)8;;/h3,6H,1-2H2,(H,7,8)(H,9,10);;/q;2*+1

Upstream product

• 21461-84-7 (2S)-tetrahydro-5-oxofuran-2-carboxylic acid 
• 56-86-0 L-glutamic acid 

Downstream Products

• 111139-20-9 (S)-2-(3,5-Dinitro-benzoyloxy)-pentanedioic acid dimethyl ester 
• 111139-23-2 (S)-2-(2,6-Dinitro-benzoyloxy)-pentanedioic acid dimethyl ester 
• 111139-21-0 (S)-2-(2-Nitro-benzoyloxy)-pentanedioic acid dimethyl ester 
• 111139-24-3 (S)-4-bromophenyl 5-oxotetrahydrofuran-2-carboxylate 
• 111139-26-5 (S)-N-(4-bromophenyl) 5-oxotetrahydrofuran-2-carboxamide 
• 111075-14-0 (S)-bis(4-bromophenyl) 2-(2,6-dinitrobenzoyloxy)pentanedioate 
• 111139-19-6 (R)-2-(3,5-Dinitro-benzoyloxy)-pentanedioic acid dimethyl ester 
• 111139-22-1 (R)-2-(2,6-Dinitro-benzoyloxy)-pentanedioic acid dimethyl ester 
• 111186-98-2 (R)-2-(2-Nitro-benzoyloxy)-pentanedioic acid dimethyl ester 
• 111139-25-4 (R)-5-Oxo-tetrahydro-furan-2-carboxylic acid 4-bromo-phenyl ester 
• 55094-97-8 (S)-dimethyl 2-hydroxypentanedioate 

Relevant articles and documents

Effect of sodium (S)-2-hydroxyglutarate in male, and succinic acid in female Wistar rats against renal ischemia-reperfusion injury, suggesting a role of the HIF-1 pathway

Background. Ischemia–reperfusion (IR) injury is the main cause of delayed graft function in solid organ transplantation. Hypoxia-inducible factors (HIFs) control the expression of genes related to preconditioning against IR injury. During normoxia, HIF-α subunits are marked for degradation by the egg-laying defective nine homolog (EGLN) family of prolyl-4-hydroxylases. The inhibition of EGLN stabilizes HIFs and protects against IR injury. The aim of this study was to determine whether the EGLN inhibitors sodium (S)-2-hydroxyglutarate [(S)-2HG] and succinic acid (SA) have a nephroprotective effect against renal IR injury in Wistar rats. Methods. (S)-2HG was synthesized in a 22.96% yield from commercially available L-glutamic acid in a two-step methodology (diazotization/alkaline hydrolysis), and its structure was confirmed by nuclear magnetic resonance and polarimetry. SA was acquired commercially. (S)-2HG and SA were independently evaluated in male and female Wistar rats respectively after renal IR injury. Rats were divided into the following groups: sham (SH), nontoxicity [(S)-2HG: 12.5 or 25 mg/kg; SA: 12.5, 25, or 50 mg/kg], IR, and compound+IR [(S)-2HG: 12.5 or 25 mg/kg; SA: 12.5, 25, or 50 mg/kg]; independent SH and IR groups were used for each assessed compound. Markers of kidney injury (BUN, creatinine, glucose, and uric acid) and liver function (ALT, AST, ALP, LDH, serum proteins, and albumin), proinflammatory cytokines (IL-1β, IL-6, and TNF-α), oxidative stress biomarkers (malondialdehyde and superoxide dismutase), and histological parameters (tubular necrosis, acidophilic casts, and vascular congestion) were assessed. Tissue HIF-1α was measured by ELISA and Western blot, and the expression of Hmox1 was assessed by RT-qPCR. Results. (S)-2HG had a dose-dependent nephroprotective effect, as evidenced by a significant reduction in the changes in the BUN, creatinine, ALP, AST, and LDH levels compared with the IR group. Tissue HIF-1α was only increased in the IR group compared to SH; however, (S)-2HG caused a significant increase in the expression of Hmox1, suggesting an early accumulation of HIF-1α in the (S)-2HG-treated groups. There were no significant effects on the other biomarkers. SA did not show a nephroprotective effect; the only changes were a decrease in creatinine level at 12.5 mg/kg and increased IR injury at 50 mg/kg. There were no effects on the other biochemical, proinflammatory, or oxidative stress biomarkers. Conclusion. None of the compounds were hepatotoxic at the tested doses. (S)2HG showed a dose-dependent nephroprotective effect at the evaluated doses, which involved an increase in the expression of Hmox1, suggesting stabilization of HIF-1α. SA did not show a nephroprotective effect but tended to increase IR injury when given at high doses.