Disease relevance of ECHS1

• We isolated cDNA clones for human SCEH to facilitate investigation of the enzyme structure of the gene and to examine the genetic background of Reye's syndrome and sudden infant death [1].
• Crystal structure of the (R)-specific enoyl-CoA hydratase from Aeromonas caviae involved in polyhydroxyalkanoate biosynthesis [2].
• Trifunctional protein deficiency, a typical mitochondrial long-chain fatty acid beta-oxidation defect, is caused by the abnormality of mitochondrial long-chain enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase trifunctional protein consisting of four moles of alpha-subunit and four moles of beta-subunit [3].
• Screening this region with additional microsatellite markers revealed that the adjacent marker D2S1374 was also significantly associated with obstetric cholestasis, whereas no association was found with the markers located in the vicinity of the hydroxyacyl-CoA dehyrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, alpha subunit (HADHA) gene [4].

High impact information on ECHS1

• Mitochondrial trifunctional protein (MTP) is a recently identified enzyme involved in mitochondrial beta-oxidation, harboring long-chain enoyl-CoA hydratase, long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and long-chain 3-ketothiolase activity [5].
• We examined the enzyme protein and biosynthesis of human trifunctional protein harboring enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase activity in cultured skin fibroblasts from two patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency [6].
• Immunoblot studies of peroxisomal beta-oxidation enzymes revealed that the bifunctional enzyme (enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase) was deficient in postmortem liver samples, whereas acyl-CoA oxidase and the mature form of beta-ketothiolase were present [7].
• The substrate, anchored through the 3'-phosphate ADP moiety, allows the fatty acid tail to pivot from the ECH to HACD active sites, and finally to the KACT active site [8].
• Cytochemical localization of catalase by the alkaline 3,3'-diaminobenzidine procedure and immunofluorescence localization of heat-labile enoyl-CoA hydratase showed that these peroxisome-associated enzymes are localized strictly in pancreatic hepatocytelike cells, while adjacent acinar, duct, and islet cells appeared consistently negative [9].

Biological context of ECHS1

• The human ECHS1 gene locus was assigned to chromosome 10q26.2-q26.3 by fluorescence in situ hybridization [10].
• Our present study highlights the usefulness of multimodality approaches in identifying genetic markers, and further describes the novel finding of ECHS1 down-regulation in the DX chemo-resistance of HCC [11].
• Comparison with the rat SCEH cDNA showed that the deduced amino acid sequence of the human SCEH precursor is 84% identical to that of the rat enzyme precursor [1].
• Oligo(dT)-primed and random primed human liver cDNA libraries in lambda gt11 were screened using the entire sequence of the rat SCEH cDNA as a probe [1].
• Subsequent mutation analysis showed that both patients are homozygous for a missense mutation (N457Y), which is located in the enoyl-CoA hydratase coding part of the D-bifunctional protein gene [12].

Anatomical context of ECHS1

• The response includes a marked proliferation of peroxisomes and enhanced activity of peroxisomal enzymes enoyl-CoA hydratase (8.5- to 13-fold), [1-14C]-palmitoyl-CoA oxidation (2.8- to 3.9-fold), catalase (1.6 to 3.4-fold), and carnitine acetyltransferase (greater than 2,000-fold) [9].
• A 78-kDa gastrin-binding protein (GBP), the sequence of which is related to the family of enzymes possessing enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase activities, has been previously purified from porcine gastric mucosal membranes [13].
• A bifunctional enzyme from glyoxysomes. Purification of a protein possessing enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase activities [14].
• Enoyl-CoA hydratase (E.C. 4.2.1.17), purified from rat-liver mitochondria, is one of the enzymes from the beta-oxidation pathway of fatty-acid metabolism; it catalyzes the reversible hydration of 2-trans-enoyl-CoA's to L-3-hydroxy-acyl-CoA's. Different crystal forms, diffracting to 3.0 A, were obtained [15].
• In skeletal muscle, heart, and liver of developing rats, we measured mitochondrial activities of long- and short-chain enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and long- and short-chain acyl-CoA thiolase [16].

Associations of ECHS1 with chemical compounds

• 2-Propyl-2-pentenoyl-CoA, a presumed intermediate in the beta-oxidation of valproic acid, was chemically synthesized and used to demonstrate that enoyl-CoA hydratase or crotonase catalyzes its hydration to 3-hydroxy-2-propylpentanoyl-CoA [17].
• Importantly, a new peroxisomal beta-oxidation enzyme was recently described called D-bifunctional protein with enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase activity primarily reacting with alpha-methyl fatty acids like pristanic acid and di- and trihydroxycholestanoic acid [18].
• Propionyl-CoA synthase is a natural fusion protein of 201 kDa consisting of a CoA ligase, an enoyl-CoA hydratase, and an enoyl-CoA reductase, the reductase domain containing the trypsin cleavage site [19].
• CarB displays sequence homology with members of the crotonase family including enoyl-CoA hydratase (crotonase) and methylmalonyl-CoA decarboxylase [20].
• The N-terminal part exhibits 3-hydroxyacyl-CoA dehydrogenase and 17beta-hydroxysteroid dehydrogenase activity whereas the central part shows enoyl-CoA hydratase activity [21].

Physical interactions of ECHS1

• The human AUH gene has been reported to encode for a bifunctional enzyme with both RNA-binding and enoyl-CoA-hydratase activity [22].

Enzymatic interactions of ECHS1

• The enoyl-CoA hydratase and beta-hydroxy acyl-CoA dehydrogenase reactions involved in the chain shortening of C27-5beta-cholestanoic acids are catalyzed by the recently identified peroxisomal d-bifunctional protein [23].

Other interactions of ECHS1

• The immediate 5'-flanking region of the ECHS1 gene is GC-rich and contains several copies of the SP1 binding motive but no typical TATA or CAAT boxes are apparent [10].
• Positional profiling further suggested the consistent down-regulation of CGI-18 and ECHS1 on chromosome 10q [11].
• Mitochondrial trifunctional protein (TP), an enzyme of beta-oxidation, is a multienzyme complex composed of four molecules of the alpha-subunit (HADHA) containing the enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase domains and four molecules of the beta-subunit (HADHB) containing the 3-ketoacyl-CoA thiolase domain [24].
• AUH exhibited dual activities, namely A+U-specific RNA-binding and catalytic activity as enoyl-CoA hydratase [25].
• We show by immunoblotting that there is a marked deficiency in livers from patients with the Zellweger syndrome of the peroxisomal beta-oxidation enzyme proteins acyl-CoA oxidase, the bifunctional protein with enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase activities and 3-oxoacyl-CoA thiolase [26].

Analytical, diagnostic and therapeutic context of ECHS1

• The array findings were substantiated by quantitative RT-PCR, which further pointed to a repressed ECHS1 expression in correlation with DX resistance (p=0.021) [11].
• Molecular cloning and sequence analysis of the cDNA for human mitochondrial short-chain enoyl-CoA hydratase [1].
• The immunocytochemical localization of catalase and three enzymes of the peroxisomal lipid beta-oxidation system--acyl-CoA oxidase, the bifunctional protein enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase--in human liver biopsies was investigated by means of light and electron microscopy [27].
• A convenient method for screening crystallization conditions using an automated fast-screen protocol has been implemented and tested on an enoyl-CoA hydratase [15].
• 1. Enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase copurified when extracts from cotyledons of 5-day-old cucumber seedlings were fractionated by acetone precipitation, ion-exchange chromatography on CM-cellulose and affinity chromatography on blue-dextran-Sepharose [14].

References