Disease relevance of ECs0751

• Acyl group and electron pair relay system: a network of interacting lipoyl moieties in the pyruvate and alpha-ketoglutarate dehydrogenase complexes from Escherichia coli [1].

High impact information on ECs0751

• A computer modeling system was used to analyze experimental data for inactivation of the Escherichia coli alpha-ketoglutarate dehydrogenase complex accompanying release of lipoic acid residues by lipoamidase and by trypsin [Stepp, L. R., Bleile, D. M., McRorie, D. K., Pettit, F. H. & Reed, L. J. (1981) Biochemistry 20, 4555-4560] [2].
• The results provide insight into the active-site coupling mechanism in the alpha-ketoglutarate dehydrogenase complex [2].
• Wild-type cells appear to be capable of compensating for the increased ATP drain due to futile cycling but cannot be as effective when a tricarboxylic acid cycle enzyme, alpha-ketoglutarate dehydrogenase, is defective [3].
• Full-length cDNA clones for succinyltransferase of the rat alpha-ketoglutarate dehydrogenase complex were isolated from rat heart cDNA libraries in lambda gt11 [4].
• Malyl-CoA formation in the NAD-, CoASH-, and alpha-ketoglutarate dehydrogenase-dependent oxidation of 2-keto-4-hydroxyglutarate. Possible coupled role of this reaction with 2-keto-4-hydroxyglutarate aldolase activity in a pyruvate-catalyzed cyclic oxidation of glyoxylate [5].

Chemical compound and disease context of ECs0751

• The alpha-ketoglutarate dehydrogenase complex from Escherichia coli catalyzes the hydrolysis of S-succinyl-CoA to succinate and CoASH [6].
• The alpha-ketoglutarate dehydrogenase complex of either pig heart or Escherichia coli catalyzes a NAD- and CoASH-dependent oxidation of 2-keto-4-hydroxyglutarate which is stereoselective toward the L-isomer of this hydroxyketo acid [5].
• The kinetics of the succinylation and the desuccinylation of the alpha-ketoglutarate dehydrogenase complex from Escherichia coli have been studied at 4 degrees C in 2 mM thiamin pyrophosphate, 2 mM MgCl2, and 20 mM potassium phosphate (pH 7.0) by steady-state and quenched-flow techniques [7].
• The lipoic acids of the alpha-ketoglutarate dehydrogenase multienzyme complex from Escherichia coli have been modified with two fluorescent probes, N-(1-pyrenyl)-maleimide and 5-[[[(iodoacetyl)amino]ethyl]amino]-naphthylene-1-sulfonic acid [8].
• Succinyl phosphonate inhibits alpha-ketoglutarate oxidative decarboxylation, catalyzed by alpha-ketoglutarate dehydrogenase complexes from E. coli and pigeon breast muscle [9].

Biological context of ECs0751

• Elementary steps in the reaction mechanism of the alpha-ketoglutarate dehydrogenase multienzyme complex from Escherichia coli: kinetics of succinylation and desuccinylation [7].
• Relieving transcriptional control of the sdhCDAB-b0725-sucABCD operon by chromosomal promoter exchange mutagenesis yielded a strain with increased specific activities of the TCA cycle enzymes succinate dehydrogenase, alpha-ketoglutarate dehydrogenase and succinyl-CoA synthetase, which are encoded by this operon [10].

Associations of ECs0751 with chemical compounds

• The major lipoylated proteins are highly conserved enzymes of central metabolism, the pyruvate and alpha-ketoglutarate dehydrogenase complexes [11].
• Several independent lines of evidence support the conclusion that this hydroxyketo acid is a substrate for the well known alpha-ketoglutarate dehydrogenase complex of the citric acid cycle [12].
• The activated form of succinic semialdehyde is derived by the action of the first enzyme of the alpha-ketoglutarate dehydrogenase complex or by a similar decarboxylase enzyme [13].
• The dihydrolipoamide succinyltransferase (E2o) component of the alpha-ketoglutarate dehydrogenase complex catalyzes the transfer of a succinyl group from the S-succinyldihydrolipoyl moiety to coenzyme A. E2o is normally a 24-mer, but is found as a trimer when E2o is expressed with a C-terminal [His]6 tag [14].
• OSB synthase and alpha-ketoglutarate dehydrogenase are similar in that both decarboxylate alpha-ketoglutarate in the presence of thiamine pyrophosphate but the enzyme systems can be separated easily by several methods [15].

Physical interactions of ECs0751

• The alpha-ketoglutarate dehydrogenase complex of Escherichia coli can bind up to 12 dimers of dihydrolipoyl dehydrogenase (E3) besides those already present [16].

Other interactions of ECs0751

• KGDC consists of an octahedral cube-shaped structural core, lipoyl transsuccinylase (E2), to which 12 polypeptide chains each of alpha-ketoglutarate dehydrogenase (E1) and dihydrolipoyl dehydrogenase (E3) are non-covalently bound [17].

Analytical, diagnostic and therapeutic context of ECs0751

• Purification and molecular cloning of succinyltransferase of the rat alpha-ketoglutarate dehydrogenase complex. Absence of a sequence motif of the putative E3 and/or E1 binding site [4].
• The quaternary structure of the alpha-ketoglutarate dehydrogenase complex (KGDC) from Escherichia coli has been investigated by electron microscopy [17].
• The self-association of Escherichia coli alpha-ketoglutarate dehydrogenase complex (KGDC) purified by a column Chromatographic technique, was characterized by light-scattering photometry [18].

References