Disease relevance of hydroxyglutarate

• Re-face stereospecificity at C4 of NAD(P) for alcohol dehydrogenase from Methanogenium organophilum and for (R)-2-hydroxyglutarate dehydrogenase from Acidaminococcus fermentans as determined by 1H-NMR spectroscopy [1].
• Thus it closely resembled the dehydration of (R)-2-hydroxyglutarate in Acidaminococcus fermentans , although an activation was not necessary [2].
• Fermentation of [1-14C]glutamic acid gives rise to butyrate labeled in the carboxyl carbon, indicating that butyrate is formed by the hydroxyglutarate pathway which may be characteristic for the genus Fusobacterium [3].
• The methylaspartate pathway was found in strains of Clostridium tetanomorphum, C. malenominatum, C. limosum, C. lentoputrescens and C. tetani, whereas the hydroxyglutarate pathway was detected in C. sporosphaeroides [4].
• The determination of enzymatic activities in cell-free extracts of Acidaminococcus fermentans and Peptostreptococcus asaccharolyticus led to a refined scheme for the pathway of glutamate fermentation via (R)-2-hydroxyglutarate to acetate and butyrate [5].

High impact information on hydroxyglutarate

• It was shown that the enzyme also catalyzes the intrinsically exergonic hydrolysis of alpha-hydroxyglutarate lactone, a reaction that is ATP-dependent [6].
• The gene gcdA is part of the 'hydroxyglutarate operon', which does not contain genes coding for the other three subunits [7].
• Extracts of cells obtained in the presence of air also had an increased amount of a complex arylamine which, on acid hydrolysis, gave 1 mol each of phosphate, 5-(p-aminophenyl)-1,2,3,4-tetrahydroxypentane, and alpha-hydroxyglutaric acid [8].
• A coupled assay with alpha-hydroxyglutarate dehydrogenase was used to analyze the kinetic behavior of histidinol phosphate aminotransferase from Salmonella typhymurium [9].
• The equilibrium constants of the reactions catalysed by (S)-citramalate lyase and (R)-2-hydroxyglutarate dehydrogenase were determined using the purified enzymes from Clostridium tetanomorphum and Acidaminococcus fermentans, respectively [10].

Chemical compound and disease context of hydroxyglutarate

• The reversible dehydration of (R)-2-hydroxyglutarate to (E)-glutaconate [11].
• After activation this purified enzyme catalysed the dehydration of (R)-2-hydroxyglutarate only in the presence of acetyl-CoA and glutaconate CoA-transferase, demonstrating that the thiol ester and not the free acid is the substrate of the dehydration [12].

Biological context of hydroxyglutarate

• Experiments with an antiserum against the enzyme indicate that the transferase is necessary for the decarboxylation of glutaconate but not for the dehydration of (R)-2-hydroxyglutarate [13].

Associations of hydroxyglutarate with other chemical compounds

• Determination of the absolute configuration of 2-hydroxyglutaric acid and 5-oxoproline in urine samples by high-resolution NMR spectroscopy in the presence of chiral lanthanide complexes [14].
• NAD(+)-dependent (R)-2-hydroxyglutarate dehydrogenase (HGDH) catalyses the reduction of 2-oxoglutarate to (R)-2-hydroxyglutarate and belongs to the d-2-hydroxyacid NAD(+)-dependent dehydrogenase (d-2-hydroxyacid dehydrogenase) protein family [15].

Gene context of hydroxyglutarate

• We determined the optical isomer of the 2-hydroxyglutaric acid (2HG) that was elevated in the urine of five Japanese children with a mild form of glutaric aciduria type II (GA2), caused by a deficiency of electron transfer flavoprotein (ETF) or ETF-ubiquinone oxidoreductase (ETF-QO) [16].
• We propose that in the hydroxyglutarate pathway these oxidoreductases work in the reverse direction, whereby the reduction of ferredoxin by NADH is driven by the Na(+) gradient [17].

Analytical, diagnostic and therapeutic context of hydroxyglutarate

• BACKGROUND: The differential diagnosis of D-2-hydroxyglutaric aciduria (D-2-HGA), L-2-hydroxyglutaric aciduria (L-2-HGA), and the combined D/L-2-hydroxyglutaric aciduria (D/L-2-HGA) can be accomplished only by the measurement of the corresponding 2-hydroxyglutarate (2-HG) [18].
• The 2-hydroxyglutaric acid was found to have the L-configuration, as analysed by capillary gas chromatography of the O-acetylated di-(-)-2-butyl ester derivative [19].
• Chiral liquid chromatography tandem mass spectrometry in the determination of the configuration of 2-hydroxyglutaric acid in urine [20].
• Proton magnetic resonance (MR) spectroscopy of the brain obtained with the hybrid chemical shift imaging sequence (repetition time = 1,500 milliseconds, echo time = 40 milliseconds) revealed prominent peaks resonating at 2.50 ppm, which were attributable to L-2 hydroxyglutaric acid [21].

References