Disease relevance of 3-hydroxypentanedioic acid

• In addition, increased excretion of 3-hydroxyglutaric acid was detected in all three patients, a finding previously observed only in glutaric aciduria type 1, ketosis, and short-chain hydroxyacyl-CoA dehydrogenase deficiency [1].
• IGF-1 and bFGF reduce glutaric acid and 3-hydroxyglutaric acid toxicity in striatal cultures [2].

High impact information on 3-hydroxypentanedioic acid

• Urine metabolite analysis showed that SCHAD deficiency resulted in specific excretion of 3-hydroxyglutaric acid [3].
• Glutaric aciduria type I (GA I) is an autosomal recessive inherited metabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase (GCD) resulting in the accumulation of 3-hydroxyglutaric acid (3OHG), glutaric acid and glutaconic acid in body fluids [4].
• Here, we demonstrate that the disease-specific metabolite 3-hydroxyglutaric acid (3-OH-GA) inhibits basal and vascular endothelial growth factor (VEGF)-induced endothelial cell migration [5].
• 3-Hydroxyglutaric acid moderately impairs energy metabolism in brain of young rats [6].
• We conclude from these results that 3-hydroxyglutaric acid and glutaric acid act as false neurotransmitters, in particular through NR1/2B, and that the extent of induced neurotoxicity is dependent on the temporal and spatial expression of NR1/2B in the CNS during maturation [7].

Biological context of 3-hydroxypentanedioic acid

• Exposure to glutaric acid and 3-hydroxyglutaric acid decreased cell viability in a concentration- and time-dependent fashion [7].
• 3-Hydroxyglutaric acid induces oxidative stress and decreases the antioxidant defenses in cerebral cortex of young rats [8].
• It was verified that the single addition of QA or GA plus 3HGA to the incubation medium significantly stimulated in vitro lipid peroxidation [9].

Anatomical context of 3-hydroxypentanedioic acid

• 3-Hydroxyglutaric acid showed the highest concentration (62 nmol/g protein) in the putamen among all brain areas investigated [10].
• For other body fluids, control ranges in mumol/l/L were: for glutaric acid 0.55-2.9 (plasma), 0.18-0.63 (cerebrospinal fluid) and 0.19-0.7 (amniotic fluid); and for 3-hydroxyglutaric acid, 0.2-1.36 (plasma), < 0.2 (cerebrospinal fluid) and 0.22-0.41 (amniotic fluid) [11].
• Nerve cell lesions caused by 3-hydroxyglutaric acid: a possible mechanism for neurodegeneration in glutaric acidaemia I [12].
• Quantification of 3-hydroxyglutaric acid in urine, plasma, cerebrospinal fluid and amniotic fluid by stable-isotope dilution negative chemical ionization gas chromatography-mass spectrometry [13].

Associations of 3-hydroxypentanedioic acid with other chemical compounds

• In organotypic corticostriatal and hippocampal slice cultures from rat brain, 3-hydroxyglutaric acid but not glutaric and glutaconic acids induced neurodegeneration by activation of NMDA receptors [14].
• The neurometabolic disorder glutaryl-CoA dehydrogenase (GCDH) deficiency is biochemically characterised by an accumulation of the marker metabolites 3-hydroxyglutaric acid, glutaric acid, and glutarylcarnitine [10].
• Glutaric acid (GA) and 3-hydroxyglutaric acid (3GA) are thought to contribute to the degeneration of the caudate and putamen that is seen in some children with glutaric acidaemia type I, a metabolic disorder caused by a glutaryl-CoA dehydrogenase deficiency [2].
• Furthermore, glutaric and 3-hydroxyglutaric acids inhibit glutamate decarboxylase, the key enzyme of GABA synthesis, and striatal GABAergic medium-spiny neurons are highly vulnerable to 3-hydroxyglutaric acid-induced neurotoxicity [15].

Gene context of 3-hydroxypentanedioic acid

• The respective values of 3-hydroxyglutaric acid were 1.4-8.0 and 2.6-11.7 mmol/mol creatnine [11].

Analytical, diagnostic and therapeutic context of 3-hydroxypentanedioic acid

• 3-Hydroxyglutaric acid in the urine was quantified by organic acid analysis via gas chromatography mass spectrometry (GCMS) and by stable isotope-dilution (internal standard) GCMS [16].

References