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evolution
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the crotonases comprise a widely distributed enzyme superfamily that has multiple roles in both primary and secondary metabolism. Enoyl-CoA hydratase (ECH) and enoyl-CoA isomerase (ECI) are prototypical crotonases. The term crotonase has been used to refer specifically to ECH, but it is also used to refer to the entirety of the superfamily of enzymes bearing the crotonase-type fold
evolution
the crotonases comprise a widely distributed enzyme superfamily that has multiple roles in both primary and secondary metabolism. Enoyl-CoA hydratase (ECH) and enoyl-CoA isomerase (ECI) are prototypical crotonases. The term crotonase has been used to refer specifically to ECH, but it is also used to refer to the entirety of the superfamily of enzymes bearing the crotonase-type fold. Some enzymes (e.g. rat peroxisomal multifunctional enzyme, type 1) have both ECH and ECI activities. These enzymes employ an active site with two glutamate residues. Rat mitochondrial ECH-1 (which has the two glutamate residues typical of ECH) has isomerase activity, albeit much lower than its hydratase activity. While the hydratase activity depends on both glutamate residues, the isomerase activity (as with dedicated ECI enzymes) relies mostly on a single glutamate
evolution
the crotonases comprise a widely distributed enzyme superfamily that has multiple roles in both primary and secondary metabolism. Enoyl-CoA hydratase (ECH) and enoyl-CoA isomerase (ECI) are prototypical crotonases. The term crotonase has been used to refer specifically to ECH, but it is also used to refer to the entirety of the superfamily of enzymes bearing the crotonase-type fold. Some enzymes, e.g. rat peroxisomal multifunctional enzyme, type 1, have both ECH and ECI activities. These enzymes employ an active site with two glutamate residues. Through the use of an additional domain, some multifunctional crotonase enzymes can also catalyze a further step in fatty acid catabolism, i.e. the oxidation of the enoyl-CoA hydratase product. While the hydratase activity depends on both glutamate residues, the isomerase activity (as with dedicated ECI enzymes) relies mostly on a single glutamate
malfunction
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siRNA-mediated knockdown of ECHS1 in the murine hepatocyte cell line alpha mouse liver 12 demonstrate increased cellular lipid accumulation induced by free fatty acid overload. Administering ECHS1 siRNA specifically reduces the expression of ECHS1 protein in mice liver, which significantly exacerbates the hepatic steatosis induced by an high fat diet
malfunction
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Ech1 shRNA interference decreases Hca-F cell proliferation and the in situ adhesive capacity of Hca-F cells to lymph nodes, phenotype, overview
malfunction
inactivation of dspI abolishes biofilm dispersion autoinduction in continuous cultures of Pseudommonas aeruginosa and results in biofilms that are significantly greater in thickness and biomass compared to the parental wild-type strain. But dispersion can be induced in dspI mutants by the exogenous addition of synthetic cis-2-decenoic acid or by complementation of DELTAdspI in trans under the control of an arabinose-inducible promoter
malfunction
deficiency of the enzyme causes an early childhood Leigh syndrome phenotype. Two homozygous truncation mutations in ECHS1 in two siblings lead to development of lethal neonatal lactic acidosis, potential genotype/phenotype correlation, overview
malfunction
mutations in ECHS1 result in short-chain enoyl-CoA hydratase (SCEH) deficiency which mainly affects the catabolism of various amino acids, particularly valine. Patients show a Leigh syndrome-like phenotype, important diagnostic markers for this disorder include S-(2-carboxypropyl)-L-cysteine and S-(2-carboxypropyl)cysteamine (which are derived from methacrylyl-CoA), S-(2-carboxyethyl)-L-cysteine and S-(2-carboxyethyl)cysteamine (which are derived from acryloyl-CoA), and 2-methyl-2,3-dihydroxybutyric acid (MDHB). In a lethal neonatal case, SCEH deficiency is confirmed with very low SCEH activity in fibroblasts and nearly absent immunoreactivity of SCEH. The patient has a severe neonatal course with elevated blood and cerebrospinal fluid (CSF) lactate and pyruvate concentrations, high plasma alanine and slightly low plasma cystine. 2-Methyl-2,3-dihydroxybutyric acid is markedly elevated as are metabolites of the three branched-chain ketoacids on urine organic acids analysis. These urine metabolites notably decrease when lactic acidosis decreases in blood. Lymphocyte pyruvate dehydrogenase complex (PDC) activity is deficient, but PDC and 2-oxoglutarate dehydrogenase complex activities in cultured fibroblasts are normal. Oxidative phosphorylation analysis on intact digitonin-permeabilized fibroblasts is suggestive of slightly reduced PDC activity relative to control range in mitochondria. Review of other cases of mutations with primary short-chain enoyl-CoA hydratase (SCEH) deficiency associated with secondary lymphocyte pyruvate dehydrogenase complex (PDC) deficiency, about half of cases with primary SCEH deficiency also exhibit secondary PDC deficiency, overview. To date, almost half of cases diagnosed with this autosomal recessive disorder perish within the neonatal or infantile period, but survival into adulthood is reported
malfunction
while mutation of Glu144 to alanine in this enzyme diminishes the isomerase activity by 10fold, mutation of Glu164 to alanine decreases the isomerase activity 1000fold, the hydratase activity is decreased 2000fold for both mutants
metabolism
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the human mitochondrial trifunctional protein enoyl-CoA hydratase is a multienzyme complex involved in fatty acid beta-oxidation. The pathway shows feed-back inhibition, overview
metabolism
two multifunctional peroxisomal isozymes, MFP2 and AIM1, both with 2-trans-enoyl-CoA hydratase and L-3-hydroxyacyl-CoA dehydrogenase activities, function in Arabidopsis thaliana peroxisomal beta-oxidation, where fatty acids are degraded by the sequential removal of two carbon units
metabolism
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the enzyme catalyzes a reaction of the beta-oxidation, overview
metabolism
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the enzyme catalyzes a reaction of the beta-oxidation, overview
metabolism
the enzyme catalyzes a reaction step of the beta-oxidation, as part of the catabolic gene cluster for phenylacetate degradation, overview
metabolism
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the enzyme catalyzes a reaction step of the beta-oxidation, overview
metabolism
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the enzyme catalyzes a reaction step of the beta-oxidation, overview
metabolism
short-chain enoyl-CoA hydratase (SCEH) is a mitochondrial enzyme involved in the oxidation of fatty acids and the catabolic pathway of valine and, to a lesser extent, isoleucine
metabolism
the prototypical crotonases enoyl-CoA hydratase (ECH) and enoyl-CoA isomerase (ECI) are crucially involved in the beta-oxidation pathway of fatty acid metabolism
metabolism
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the prototypical crotonases enoyl-CoA hydratase (ECH) and enoyl-CoA isomerase (ECI) are crucially involved in the beta-oxidation pathway of fatty acid metabolism
metabolism
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the enzyme catalyzes a reaction step of the beta-oxidation, overview
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physiological function
the multifunctional enzyme is involved in an alpha-methylacyl-CoAracemase-MFE2 independent synthesis pathway of bile acids from (24S)-hydroxyoxisterols, is involved in the beta-oxidation of long chain dicarboxylic acids
physiological function
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FadRBs or YsiA is a transcriptional regulatory protein which negatively regulates the expression of beta-oxidation genes including those belonging to the lcfA operon, including fadRBs or ysiA. FadBBs is active in the hydratation of crotonyl-CoA, supporting the possibility of its direct involvement in the beta-oxidation pathway
physiological function
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recombinant enoyl-CoA hydratase displays 2-enoyl-CoA hydratase, L-3-hydroxyacyl-CoA dehydrogenase, EC 1.1.1.35, and 3-ketoacyl-CoA thiolase, EC 2.3.1.16, activities
physiological function
enoyl-CoA hydratase is one of the enzymes involved in the peroxisomal beta-oxidation cycle
physiological function
the enzyme is responsible for catalyzing the formation of alpha,beta-unsaturated fatty acids and dspI is essential for production of cis-2-decenoic acid, and it is required for synthesis of the biofilm dispersion autoinducer cis-2-decenoic acid in the human pathogen Pseudomonas aeruginosa. Expression of dspI is correlated with cell density during planktonic and biofilm growth
physiological function
prototypical crotonase enoyl-CoA hydratase (ECH) and enoyl-CoA isomerase (ECI) are crucially involved in the beta-oxidation pathway of fatty acid metabolism. Enzyme ECH catalyzes the second step of the beta-oxidation pathway: i.e. the syn addition of a water molecule across the double bond of an alpha,beta-unsaturated enoyl-CoA thioester substrate, e.g. crotonyl or methacrylyl-CoA
physiological function
prototypical crotonase enoyl-CoA hydratase (ECH) is crucially involved in the beta-oxidation pathway of fatty acid metabolism. Enzyme ECH catalyzes the second step of the beta-oxidation pathway: i.e. the syn addition of a water molecule across the double bond of an alpha,beta-unsaturated enoyl-CoA thioester substrate, e.g. crotonyl or methacrylyl-CoA. Rat mitochondrial ECH-1 (which has the two glutamate residues typical of ECH) has isomerase activity, albeit much lower than its hydratase activity
physiological function
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prototypical crotonase enoyl-CoA hydratase (ECH) is crucially involved in the beta-oxidation pathway of fatty acid metabolism. Enzyme ECH catalyzes the second step of the beta-oxidation pathway: i.e. the syn addition of a water molecule across the double bond of an alpha,beta-unsaturated enoyl-CoA thioester substrate, e.g. crotonyl or methacrylyl-CoA. The enzyme is also involved in the formation of vanillin, combined with aldolase activity
physiological function
the enzyme is the second requisite enzyme in the beta-oxidation pathway of fatty acids that catalyzes the syn hydration of alpha,beta-unsaturated thiolester substrates
physiological function
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FadRBs or YsiA is a transcriptional regulatory protein which negatively regulates the expression of beta-oxidation genes including those belonging to the lcfA operon, including fadRBs or ysiA. FadBBs is active in the hydratation of crotonyl-CoA, supporting the possibility of its direct involvement in the beta-oxidation pathway
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additional information
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key role of ECHS1 and PRDX3 in regulation of 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, PP2, -induced apoptosis, downregulation of ECHS1 and PRDX3 potentiates PP2-induced apoptosis in MCF-7 cells, overview
additional information
identification of residues involved in the ligand-enzyme interaction, homology modeling: the carbonyl group of hexadienoyl-CoA forms H-bonds with Ala32, Gly34, Val36 and Gly83. Phosphate groups of the substrate form two ionic bonds with Arg28. The enzyme shows few distinct structural changes which include structural variation in the mobile loop, formation and loss of certain interactions between the active site residues and substrates. AMECH is a monofunctional enzyme and has one catalytic glutamic acid Glu106, an essential catalytic residue. Asp114 might also be involved in the reaction mechanism, overview
additional information
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identification of residues involved in the ligand-enzyme interaction, homology modeling: the carbonyl group of hexadienoyl-CoA forms H-bonds with Ala32, Gly34, Val36 and Gly83. Phosphate groups of the substrate form two ionic bonds with Arg28. The enzyme shows few distinct structural changes which include structural variation in the mobile loop, formation and loss of certain interactions between the active site residues and substrates. AMECH is a monofunctional enzyme and has one catalytic glutamic acid Glu106, an essential catalytic residue. Asp114 might also be involved in the reaction mechanism, overview
additional information
transcript abundance of dspI correlates with cell density
additional information
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transcript abundance of dspI correlates with cell density
additional information
molecular mechanism analysis by density functional theory methods, overview. Residue Glu164 functions as the acid/base in catalysis. And although Glu144 is not directly involved in hydration, it induces the catalytic water molecule to locate in ideal orientation to attack the double bond of substrate by hydrogen-bonding interaction. The backbone NH groups of Ala98 and Gly141 form an oxyanion whole with substrate carbonyl oxygen, playing a key role in substrate binding and stabilization of generated transition states and intermediates