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3-hydroxy-3-methylglutaric acid |
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CHEBI:16831 |
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A dicarboxylic acid that is glutaric acid in which one of the two hydrogens at position 3 is substituted by a hydroxy group, while the other is substituted by a methyl group. It has been found to accumulate in urine of patients suffering from HMG-CoA lyase (3-hydroxy-3-methylglutaryl-CoA lyase, EC 4.1.3.4) deficiency. It occurs as a plant metabolite in Crotalaria dura. |
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This entity has been manually annotated by the ChEBI Team.
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CHEBI:391, CHEBI:1524, CHEBI:20043, CHEBI:43804, CHEBI:11044, CHEBI:30919, CHEBI:18746
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ChemicalBook:CB1454369, eMolecules:520938, MolPort-000-883-332, ZINC000000001669 |
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Molfile
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SDF
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more structures >>
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InChI=1S/C6H10O5/c1-6(11,2-4(7)8)3-5(9)10/h11H,2-3H2,1H3,(H,7,8)(H,9,10) |
NPOAOTPXWNWTSH-UHFFFAOYSA-N |
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Bronsted acid
A molecular entity capable of donating a hydron to an acceptor (Bronsted base).
(via oxoacid )
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plant metabolite
Any eukaryotic metabolite produced during a metabolic reaction in plants, the kingdom that include flowering plants, conifers and other gymnosperms.
human metabolite
Any mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
antimetabolite
A substance which is structurally similar to a metabolite but which competes with it or replaces it, and so prevents or reduces its normal utilization.
EC 1.1.1.34/EC 1.1.1.88 (hydroxymethylglutaryl-CoA reductase) inhibitor
Any EC 1.1.1.* (oxidoreductase acting on donor CH-OH group, NAD+ or NADP+ acceptor) inhibitor that inhibits HMG-CoA reductases. Hydroxymethylglutaryl-CoA reductase inhibitors have been shown to lower directly cholesterol synthesis. The Enzyme Commission designation is EC 1.1.1.34 for the NADPH-dependent enzyme and EC 1.1.1.88 for an NADH-dependent enzyme.
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anticholesteremic drug
A substance used to lower plasma cholesterol levels.
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View more via ChEBI Ontology
3-hydroxy-3-methylpentanedioic acid
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meglutol
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ChemIDplus
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méglutol
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WHO MedNet
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meglutol
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WHO MedNet
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meglutolum
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WHO MedNet
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(S)-3-Hydroxy-3-methylglutaric acid
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KEGG COMPOUND
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(S)-Meglutol
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KEGG COMPOUND
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3-HYDROXY-3-METHYL-GLUTARIC ACID
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PDBeChem
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3-Hydroxy-3-methylpentanedioic acid
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KEGG COMPOUND
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beta-Hydroxy-beta-methylglutaric acid
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KEGG COMPOUND
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β-hydroxy-β-methylglutaric acid
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ChEBI
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Dicrotalic acid
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KEGG COMPOUND
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1670
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DrugCentral
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C00001187
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KNApSAcK
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C03761
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KEGG COMPOUND
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CPD-547
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MetaCyc
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D04897
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KEGG DRUG
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DB04377
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DrugBank
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HMDB0000355
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HMDB
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MAH
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PDBeChem
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View more database links |
1769194
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Reaxys Registry Number
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Reaxys
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503-49-1
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CAS Registry Number
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KEGG COMPOUND
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503-49-1
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CAS Registry Number
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ChemIDplus
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Leipnitz G, Seminotti B, Haubrich J, Dalcin MB, Dalcin KB, Solano A, de Bortoli G, Rosa RB, Amaral AU, Dutra-Filho CS, Latini A, Wajner M (2008) Evidence that 3-hydroxy-3-methylglutaric acid promotes lipid and protein oxidative damage and reduces the nonenzymatic antioxidant defenses in rat cerebral cortex. Journal of neuroscience research 86, 683-693 [PubMed:17941049] [show Abstract] In the present work we investigated the in vitro effect of 3-hydroxy-3-methylglutarate (HMG) that accumulates in 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGLD) on important parameters of oxidative stress in rat cerebral cortex. It was observed that HMG induced lipid peroxidation by significantly increasing chemiluminescence and levels of thiobarbituric acid-reactive substances (TBA-RS). This effect was prevented by the antioxidants alpha-tocopherol, melatonin, N-acetylcysteine, and superoxide dismutase plus catalase, suggesting that free radicals were involved in the lipid oxidative damage. On the other hand, HMG did not change TBA-RS levels in intact or disrupted mitochondrial preparations, indicating that generation of oxidants by this organic acid was dependent on cytosolic mechanisms. HMG also induced protein oxidative damage in cortical supernatants, which was reflected by increased carbonyl content and sulfhydryl oxidation. Furthermore, HMG significantly reduced the nonenzymatic antioxidant defenses total-radical trapping antioxidant potential, total antioxidant reactivity, and reduced glutathione (GSH) levels in rat cerebral cortex. HMG-induced GSH reduction was totally blocked by melatonin pretreatment. We also verified that the decrease of GSH levels provoked by HMG in cortical supernatants was not due to a direct oxidative effect of this organic acid, because exposition of commercial GSH and purified membrane protein-bound thiol groups to HMG in the absence of cortical supernatants did not decrease the reduced sulfhydryl groups. Finally, the activities of the main antioxidant enzymes were not altered by HMG exposure. Our data indicate that oxidative stress elicited in vitro by HMG may possibly contribute at least in part to the pathophysiology of the brain injury in HMGLD. | Koling S, Kalhoff H, Schauerte P, Lehnert W, Diekmann L (2000) [3-hydroxy-3-methylglutaraciduria (case report of a female Turkish sisters with 3-hydroxy-3- methylglutaryl-Coenzyme A lyase deficiency]. Klinische Padiatrie 212, 113-116 [PubMed:10916782] [show Abstract] 3-Hydroxy-3-methylglutaric aciduria is a rare inborn error of metabolism, caused by reduced enzyme activity of the intramitochondrial 3-hydroxy-3-methylglutaryl-CoA lyase. We describe two turkish sisters with this disease. In the older sister clinical symptoms with lethargy, convulsions, metabolic acidosis, hypoglycemia and hyperammonemia lead to the diagnosis. The younger sister was diagnosed prenatally. The clinical course of our patients is compared with those reported in the literature with respect to clinical symptoms, differential diagnosis and therapeutic regimens. | Eirís J, Ribes A, Fernández-Prieto R, Rodríguez-García J, Rodríguez-Segade S, Castro-Gago M (1998) [3-hydroxy-3-methylglutaric aciduria and recurrent Reye-like syndrome]. Revista de neurologia 26, 911-914 [PubMed:9658458] [show Abstract]
Introduction3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMG-CoA lyase) is an inborn error of ketogenesis and Leucine catabolism. HMG-CoA lyase catalyses the final step in leucine degradation, converting HMG-CoA to acetyl-CoA and acetoacetic acid. Clinical manifestations include hepatomegaly, lethargy or coma and apnoea. Biochemically there is a characteristic absence of ketosis with hypoglycemia, acidosis, hipertransaminasemia and variable hyperammoniemia. The urinary organic acid profile includes elevated concentrations of 3-hydroxy-3-isovaleric, 3-hydroxy-3-methylglutaric, 3-methylglutaconic and 3-methylglutaric acids.Clinical caseHere, we report the case of a 17-year-old girl who presented in both ten months and five years of age a clinical picture characterized by lethargy leading to apnea and coma, hepatomegaly, hypoglycemia, metabolic acidosis, hyperammoniemia, elevated serum transaminases and absence of ketonuria. Diagnostic of Reye syndrome was suggested by hystopathologic finding of hepatic steatosis and clinical and biochemical data. As of 11 years old, laboratory investigations revealed carnitine deficiency and characteristic aciduria. Confirmatory enzyme diagnosis revealing deficiency of HMG-CoA lyase was made in cultured fibroblasts.ConclusionOur report constitutes an example of the presentation of HMG-CoA lyase deficiency as recurrent Reye-like syndrome. | Gibson KM, Breuer J, Nyhan WL (1988) 3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: review of 18 reported patients. European journal of pediatrics 148, 180-186 [PubMed:3063529] [show Abstract] 3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMG-CoA lyase) is an inborn error of leucine catabolism which often leads to life-threatening illness in the neonatal period. The cardinal clinical features include severe infantile hypoglycemia, metabolic acidosis, hepatomegaly, lethargy or coma and apnea. Hyperammonemia is variable. There is a characteristic absence of ketosis. Considerable heterogeneity has been observed in clinical and biochemical presentation. Acute episodes of illness have been mistaken for Reye syndrome. The pattern of organic acids in the urine includes large amounts of 3-hydroxy-3-methylglutaric, 3-methyl-glutaconic, 3-methylglutaric and 3-hydroxyisovaleric acids. Smaller, but appreciable levels of glutaric, adipic and other dicarboxylic acids may also be excreted in the urine. Lactic acid may be present in sizable amounts at times of acute illness. The primary defect is a deficiency of 3-hydroxy-3-methylglutaryl-coenzyme A lyase, a key enzyme in the cycle of ketogenesis. | Di Padova C, Di Padova F, Buzzetti M, Tritapepe R (1984) Effect of 3-hydroxy-3-methylglutaric acid administration on bile lipid composition in humans. Scandinavian journal of gastroenterology 19, 820-823 [PubMed:6083597] [show Abstract] The effects of the lipid-lowering agent 3-hydroxy-3-methylglutaric acid (HMGA) on serum lipids and on biliary lipid composition were evaluated in a double-blind, placebo-controlled study in normolipidemic volunteers. After 4 weeks of HMGA administration (1 g three times a day orally) serum total cholesterol showed a significant decrease with regard to both pretreatment values and corresponding values of controls. The bile lipid molar percentage composition and the cholesterol saturation index showed no modification after HMGA and did not differ from the values obtained in the placebo group. These findings indicate that HMGA exerts no adverse effects on bile lipid composition in humans, differing from other hypolipidemic drugs currently in clinical use, which increase the bile cholesterol saturation index. | Ahmad N, Siddiqi M (1973) Bacterial metabolism of 3-hydroxy-3-methylglutaric acid. Journal of bacteriology 115, 162-167 [PubMed:4717513] [show Abstract] An organism belonging to Pseudomonadaceae and capable of utilizing 3-hydroxy-3-methylglutarate as sole carbon source has been isolated from soil. Whole-cell preparations catalyze the oxidation of acetoacetate, acetate, glyoxylate, and citric acid cycle intermediates. Cell-free extracts of 3-hydroxy-3-methylglutarate-grown cells show an adenosine triphosphate, coenzyme A (CoA), and Mg(2+)-dependent conversion of 3-hydroxy-3-methylglutarate to 3-hydroxy-3-methylglutaryl-CoA. Succinyl-CoA-generating system has no effect on the activation and catabolism of 3-hydroxy-3-methylglutarate. |
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