Disease relevance of GLUTARIC ACID

• Glutaryl 7-aminocephalosporanic acid (GL-7-ACA) acylase of Pseudomonas sp. strain GK16 catalyzes the cleavage of the amide bond in the GL-7-ACA side chain to produce glutaric acid and 7-aminocephalosporanic acid (7-ACA) [1].
• Inactivation of rhinovirus on human fingers by virucidal activity of glutaric acid [2].
• Glutaryl-CoA dehydrogenase deficiency is an inherited metabolic disease characterized by elevated concentrations of glutaric acid (GA) and its metabolites glutaconic acid (GC) and 3-hydroxy-glutaric acid (3-OH-GA) [3].
• In two siblings with dystonic cerebral palsy the urinary metabolic profiles of organic acids were dominated by glutaric acid, a metabolite not normally present in urine [4].
• In the case of neonatal systemic hypoxia, there is no doubt about which of the equations applies, and similarly in metabolic disease, a glutaric acid urea is a direct consequence of the crossover response of metabolism and signifies that an enzyme deficiency may be involved [5].

Psychiatry related information on GLUTARIC ACID

• We postulate that the accumulation of glutaric acid and other metabolites was responsible for the child developing the associated learning disability [6].

High impact information on GLUTARIC ACID

• In the other, a marked elevation of glutaric acid in the amniotic fluid, together with deficiency of glutaryl-CoA dehydrogenase in amniotic cells, prompted termination of the pregnancy, and studies on the abortus confirmed the diagnosis of glutaric acidemia [7].
• The Gcdh-/- mice have a biochemical phenotype very similar to human GA-I patients, including elevations of GA and 3-OHGA at levels similar to those seen in GA-I patients [8].
• Patients accumulate glutaric acid (GA) and 3-OH glutaric acid (3-OHGA) in their blood, urine and CSF [8].
• In contrast to alpha-ketoglutarate dehydrogenase complex, no direct inhibition of glutaryl-CoA, glutaric acid, and 3-hydroxyglutaric acid was found in other enzymes tested [9].
• The adult fruit-eating bat, Rousettus aegypticus, excretes massive amounts of glutaric acid in the urine (20-70 mumol/mg creatinine) comparable to those of humans affected with the inherited metabolic disorder, glutaric aciduria type I. Glutaric acid was quantified by sequential liquid partition chromatography and gas chromatography [10].

Chemical compound and disease context of GLUTARIC ACID

• The second boy suffered from acute gastroenteritis and hyperthyroidism, when an excessively high urinary glutaric acid excretion was identified (1460 mmol/mol creatinine) [11].
• Conjugates of mitomycin C (MMC) with estradiol bezoate and estradiol via glutaric acid (EB-glu-MMC and E-glu-MMC, respectively) were examined for their antitumor activities against P388 leukemia and sarcoma 180 [12].
• The gene encoding cephalosporin acylase, which hydrolyzes 7-beta-(4-carboxybutanamido)-cephalosporanic acid (GL-7ACA) to 7-aminocephalosporanic acid (7ACA) and glutaric acid, was cloned from a Pseudomonas sp. strain V22 and expressed in Escherichia coli, in a two-cistron system, and the enzyme was purified and characterized [13].

Biological context of GLUTARIC ACID

• GM1 ganglioside prevents seizures, Na+,K+-ATPase activity inhibition and oxidative stress induced by glutaric acid and pentylenetetrazole [14].
• A new covalent active site reagent, 1-chloro-2-oxo-6-hexanol 6-phosphate, has been synthesized from glutaric acid monomethyl ester and characterized by NMR spectroscopy [15].
• Glutaric acid moderately compromises energy metabolism in rat brain [16].
• The effect of glutaric acid on the rate of oxygen consumption in intact mitochondria from the rat cerebrum was also investigated [16].
• Considering that the underlying mechanisms of basal ganglia damage in this disorder are poorly known, in the present study we tested the effects of glutaric acid (0.2-5mM) on critical enzyme activities of energy metabolism, namely the respiratory chain complexes I-IV, succinate dehydrogenase and creatine kinase in midbrain of developing rats [16].

Anatomical context of GLUTARIC ACID

• Chronic treatment with glutaric acid induces partial tolerance to excitotoxicity in neuronal cultures from chick embryo telencephalons [17].
• Levels of glutaric acid in plasma and cerebrospinal fluid remained unchanged, which may in part explain the overall unsatisfactory outcome [18].
• If there is suspicion of glutaric aciduria, glutaryl-coenzyme A dehydrogenase should be measured in fibroblasts or lymphocytes even if glutaric acid is not increased in the urine [19].
• Findings from an experiment in which rats had their ureters ligated showed that the inhibitory effect of glutaric acid on the renal tubular uptake of mercury was due to inhibition of the uptake of mercury at the basolateral membrane [20].
• In addition, in the presence of extracellular Na+ concentrations, the same dose of glutaric acid decreased by about 30% [3H]glutamate binding to brain plasma membranes [21].

Associations of GLUTARIC ACID with other chemical compounds

• Therefore, we investigated the effect of 3-hydroxyglutaric acid and glutaric acid on primary neuronal cultures from chick embryo telencephalons and mixed neuronal and glial cell cultures from neonatal rat hippocampi [22].
• They are also inhibited to varying degrees by aldose reductase inhibitors such as sorbinil, alrestatin, quercetrin, tetramethylene glutaric acid, and sodium phenobarbital [23].
• The metabolic hallmark of glutaric aciduria type I (GA I) is the deficiency of glutaryl-CoA dehydrogenase (GCDH) with subsequent accumulation of glutaric acid, 3-hydroxglutaric acid (3-OH-GA) and glutaconic acid [24].
• Three new coumarins, phellodenols F-H (1-3) and a new glutaric acid derivative, phellodendric acid-A (4) were isolated from the leaves of Phellodendron amurense together with twenty-nine known compounds [25].
• Gas chromatography/mass spectrometry analysis revealed abnormally high levels of glutaric acid, dicarboxylic acids, and glycine derivatives in urine [26].

Gene context of GLUTARIC ACID

• Furthermore, increasing the 23-membered lactam ring of 1 by one carbon atom (succinyl --> glutaric acid linker) gives a highly selective and potent antagonist 9 for the hMC3 receptor [27].
• Glutaric acid (GA) and 3-hydroxyglutaric acids (3-OH-GA) are key metabolites in glutaryl co-enzyme A dehydrogenase (GCDH) deficiency and are both considered to be potential neurotoxins [28].
• Nonpeptide renin inhibitors employing a novel 3-aza(or oxa)-2,4-dialkyl glutaric acid moiety as a P2/P3 amide bond replacement [29].
• As controls, we also evaluated 54 subjects with glutaric aciduria secondary to other causes (16-7509 mmol/mol creatinine; reference range: <15; no significant amounts of 3-hydroxy glutaric acid detectable) [30].
• A novel Co-glutarate, Co[O(2)C(CH(2))(3)CO(2)] (1), was synthesized as single crystals by the hydrothermal reaction of CoCl(2) with glutaric acid in the presence of KOH and characterized by single-crystal X-ray diffraction analysis, TGA, IR, UV-vis reflectance spectrometry, and SQUID measurements [31].

Analytical, diagnostic and therapeutic context of GLUTARIC ACID

• In one, in which the fetus was not affected, glutaric acid was not detected in the amniotic fluid at amniocentesis (15 weeks) and the glutaryl-CoA dehydrogenase activity of cultured amniotic cells was normal [7].
• Hand lotion containing 2% glutaric acid was significantly more effective than placebo in inactivating rhinovirus serotype 2 on the fingers of human volunteers [2].
• A substantial number of patients show only slightly, intermittently elevated or even normal urinary excretion of glutaric acid, which makes early diagnosis and treatment to prevent the severe neurological sequelae difficult [32].
• An animal model is necessary to test possible intervention strategies, and prior reports suggested that GA or 3-OH-GA could be used to create specific neuron loss in adult rats [33].
• Therefore, the initial aim of the present work was to induce high glutaric acid (GA) concentrations in rat brain similar to those found in GAI patients through subcutaneous injection of GA [34].

References