Disease relevance of glutaryl-CoA

• Cloning of glutaryl-CoA dehydrogenase cDNA, and expression of wild type and mutant enzymes in Escherichia coli [1].
• PURPOSE OF REVIEW: The hydroxymethyl glutaryl coenzyme A reductase inhibitors or statins offer important benefits for the large populations of individuals at high risk for coronary heart disease [2].
• The adult bat, with its huge glutaric acid excretion and deficient liver glutaryl-CoA dehydrogenase, metabolically mimics patients affected with glutaric aciduria type I. The bat does not, however, display the neurologic manifestations seen in patients [3].
• The exchange of oxygen atoms between acetate, glutaryl-CoA, and the catalytic glutamate residue in glutaconate CoA-transferase from Acidaminococcus fermentans was analyzed using [(18)O(2)]acetate together with matrix-assisted laser desorption/ionization time of flight mass spectrometry of an appropriate undecapeptide [4].
• Although diabetes is a major cause of chronic kidney disease (CKD), limited data describe the cardiovascular benefit of hydroxymethyl glutaryl CoA reductase inhibitors (statins) in people with both of these conditions [5].

Psychiatry related information on glutaryl-CoA

• Growing evidence indicates that some metabolites derived from the kynurenine pathway, the major route of L: -tryptophan catabolism, are involved in the neurotoxicity associated with several brain disorders, such as Huntington's disease, Parkinson's disease and Alzheimer's disease, as well as in glutaryl-CoA dehydrogenase deficiency (GAI) [6].

High impact information on glutaryl-CoA

• Other sterol-responsive genes (LDL receptor and hydroxymethyl glutaryl CoA reductase) also showed evidence of altered regulation with decreased abundance of their mRNAs in the E0 background [7].
• Specific glutaryl-CoA dehydrogenating activity is deficient in cultured fibroblasts from glutaric aciduria patients [8].
• To solve this problem, we fractionated five short-chain acyl-CoA dehydrogenases (isovaleryl-CoA, n-butyryl-CoA, isobutyryl-CoA, n-octanoyl-CoA, and glutaryl-CoA dehydrogenases) from rat liver mitochondria by isoelectric focusing and DEAE-cellulose column chromatography [9].
• The primary translation product from in vitro transcribed glutaryl-CoA dehydrogenase mRNA is translocated into mitochondria and processed in the same manner as most other nuclear-encoded mitochondrial proteins [1].
• Human glutaryl-CoA dehydrogenase shows 53% sequence similarity to porcine medium chain acyl-CoA dehydrogenase, and these similarities were utilized to predict structure-function relationships in glutaryl-CoA dehydrogenase [1].

Chemical compound and disease context of glutaryl-CoA

• Experiments were designed to assess the effectiveness of lovastatin, a 3-hydroxy-3-methyl glutaryl-CoA reductase inhibitor, and celecoxib a cyclooxygenase-2 inhibitor, individually or in combination on the induction of apoptosis in human HT-29 colon cancer cells [10].
• The efficacy of simvastatin, a competitive inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A reductase, was investigated in 12 patients treated with continuous ambulatory peritoneal dialysis (CAPD), displaying hypercholesterolemia and moderate hypertriglyceridemia [11].

Biological context of glutaryl-CoA

• Apoptosis was induced using the hydroxymethyl glutaryl CoA reductase inhibitor, lovastatin, and was evaluated by agarose gel electrophoresis of genomic DNA, morphological criteria, and terminal deoxynucleotidyl transferase-mediated nick end labeling [12].
• The function of Arg-94 in the oxidation and decarboxylation of glutaryl-CoA by human glutaryl-CoA dehydrogenase [13].
• In conclusion, our results demonstrate that bioenergetic impairment may play an important role in the pathomechanisms underlying neurodegenerative changes in glutaryl-CoA dehydrogenase deficiency [14].
• Glutaryl-CoA dehydrogenase is the only member of the acyl-CoA dehydrogenase family with a cationic residue, Arg-94, situated in the binding site of the acyl moiety of the substrate [13].
• The effect of reagents that increase membrane fluidity on the activity of 3-hydroxyl-3-methyl glutaryl coenzyme A reductase in the CHO-K1 cell [15].

Anatomical context of glutaryl-CoA

• 3-Hydroxy-3-methyl glutaryl coenzyme A reductase inhibition modulates vasopressin-stimulated Ca2+ responses in rat A10 vascular smooth muscle cells [16].
• This may be explained by conservation of glutaryl-CoA dehydrogenase activity in the central nervous system of the bat [3].
• A severe deficiency of glutaryl-CoA dehydrogenase activity was found in the bat liver and kidney, whereas brain and spinal cord levels were similar to those in the rat [3].
• The effect of insulin and catecholamines on the activities of 3-hydroxy-3-methyl glutaryl coenzyme A reductase and acyl-coenzyme A: cholesterol-o-acyltransferase in isolated rat hepatocytes [17].
• In addition, all the tested sterols were able to inhibit hydroxymethyl glutaryl-coenzyme A reductase activity in intact myocytes but not in cell-free extracts [18].

Associations of glutaryl-CoA with other chemical compounds

• We developed a new assay specific for glutaryl-CoA dehydrogenation which measures enzyme-catalyzed tritium release from [2,3,4-3H]glutaryl-CoA, and we studied the glutaryl-CoA dehydrogenating activity in cultured normal human fibroblasts and those from patients with GA [8].
• All four had undetectable glutaryl-CoA dehydrogenase activity on fibroblast culture and massive urinary excretion of glutaric acid [19].
• Pretreatment of cells with the hydroxymethyl glutaryl-CoA reductase inhibitor lovastatin blocked stimulation of JNK1 activity by UV irradiation and by treatment with the alkylating compound methyl methanesulfonate but did not affect activation of extracellular signal-regulated kinase 2 by UV light [20].
• In the present study we have found that the gene for beta-hydroxy-beta-methyl glutaryl coenzyme A reductase, a major rate-limiting enzyme in the biogenesis of mevalonate, is also hypomethylated at both CCGG and GCGC sites and expressed in hepatic nodules [21].
• Of nine known ACDs, glutaryl-CoA dehydrogenase (GCD) is unique: in addition to the alpha,beta-dehydrogenation reaction, common to all ACDs, GCD catalyzes decarboxylation of glutaryl-CoA to produce CO(2) and crotonyl-CoA [22].

Gene context of glutaryl-CoA

• When the hydroxymethyl glutaryl coenzyme A reductase promoter was used to express DP-1, overexpression occurred in a variety of tissues and did not confer phenotypic changes [23].
• Bioenergetics in glutaryl-coenzyme A dehydrogenase deficiency: a role for glutaryl-coenzyme A [14].
• In purified enzymes, glutaryl-CoA but not glutaric or 3-hydroxyglutaric induced an uncompetitive inhibition of alpha-ketoglutarate dehydrogenase complex activity [14].
• Its main characteristics are described and compared with those of glutaryl-CoA dehydrogenase (EC 1.3.99.7) and palmitoyl-CoA oxidase (EC 1.1.3.-) [24].
• Acute profound dystonia developed in three previously well infants who were found to have glutaryl-CoA dehydrogenase deficiency in cultured skin fibroblasts [25].

Analytical, diagnostic and therapeutic context of glutaryl-CoA

• Human glutaryl-CoA dehydrogenase showed a reaction of only partial identity when compared to porcine glutaryl-CoA dehydrogenase by Ouchterlony double immunodiffusion analysis using antiserum raised against and monospecific for porcine glutaryl-CoA dehydrogenase [26].
• Natural history, outcome, and treatment efficacy in children and adults with glutaryl-CoA dehydrogenase deficiency [27].
• Among the seven ddDNAs overexpressed in GIC from tolerant allografts, the 3-hydroxy-3-methyl glutaryl coenzyme-A reductase (A:M29249) and an "unknown gene" (ddDNA EC9) were identified and both were confirmed to be up-regulated by quantitative RT/PCR [28].
• Determination of the novel hydroxymethyl glutaryl coenzyme A reductase inhibitor (RP 61969) and its dihydroxy acid hydrolysis product in human plasma by reversed-phase high-performance liquid chromatography [29].
• Early prenatal diagnosis in two pregnancies at risk for glutaryl-CoA dehydrogenase deficiency [30].

References