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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 40% reduction of the diameter of the ascending aorta maintained for 60 days induced the formation of a compensate cardiac hypertrophy in rabbits without changing the value of the azide insensitive Ca2+-ATPase activity in comparison to control hearts. The cardiac mitochondria isolated from constricted animals assayed in presence of glutamate and succinate did not show a change in the R.C.I. and ADP/O values in comparison to the controls, whilst the QO2 value enhanced or decreased respectively when determined with glutamate or succinate. The intramuscular injections of CoQ10 (12 mg/kg body weight/48 h) enhanced the mitochondrial CoQ10 concentrations both in the control and in the constricted animals and further increased the QO2 value determined in both groups of animals when glutamate was used as the substrate. The production of O2.- radicals by the level of the complexes I and III of the respiratory chain, did not change in the constricted animals, nor in the animals administered with CoQ10 in comparison to the control. CoQ10 augmented the rate of oxygen consumption by the submitochondrial particles only in the constricted animals. Moreover, the treatment with the coenzyme or the constriction of the aorta, did not modify the cardiac superoxide dismutase activity, but increased the glutathione peroxidase activity only in the banded animals. In addition, in the CoQ10 treated animals there was a reduction of NADH-diaphorase activity both in the control and constricted animals, while the malondialdehyde, generated during the thiobarbituric acid test, and the cardiac content of lipofuscin were decreased.
J Mol Cell Cardiol 1987 Jan
PMID:The effect of treatment with coenzyme Q10 on the mitochondrial function and superoxide radical formation in cardiac muscle hypertrophied by mild aortic stenosis. 303 17

Site-directed mutagenesis of the aceF gene of Escherichia coli was used to generate a nested set of deletions in the long (alanine + proline)-rich sequence that separates the lipoyl domain from the dihydrolipoamide dehydrogenase-binding domain in the "one-lipoyl domain" dihydrolipoamide acetyltransferase polypeptide chains of a pyruvate dehydrogenase multienzyme complex. The deletions reduced the number of residues in this sequence successively from 32 to 20, 13, 7 and just 1 residue. In all instances, pyruvate dehydrogenase complexes were still assembled in vivo around cores containing the deleted chains, and those with the two shortest deletions were essentially fully active. However, the two most severe deletions caused falls of 50% or more in specific catalytic activity. Similarly, although shortening the interdomain sequence to 20 residues left the system of active-site coupling unimpaired, cutting it to 13 residues or less caused substantial falls in the reductive acetylation of the lipoyl domains and corresponding losses of active-site coupling. The changes in specific catalytic activity and active-site coupling that accompanied the shortening of the (alanine + proline)-rich segment were reflected in the poorer growth rates of the relevant strains of E. coli on stringent substrates. All these results are consistent with this (alanine + proline)-rich sequence acting as a linker region that facilitates the movements of the lipoyl domains required for full catalytic activity and active-site coupling in the complex. The other two such sequences that separate the additional lipoyl domains in the N-terminal half of the wild-type "three-lipoyl domain" dihydrolipoamide acetyltransferase chain are presumed to function similarly. This role is consistent with the conformational flexibility assigned to these segments from previous studies based on 1H nuclear magnetic resonance spectroscopy and protein engineering.
J Mol Biol 1988 Jul 05
PMID:Investigation of the mechanism of active site coupling in the pyruvate dehydrogenase multienzyme complex of Escherichia coli by protein engineering. 305 Jan 22

In eight New Zealand white male rabbits the abdominal aorta and one iliofemoral artery was balloon deendothelialized (group A). After 2 weeks they were kept for 6 weeks on a high cholesterol diet together with eight unoperated rabbits (group B). Eight more rabbits were kept on a commercial diet only (group C). The degree of atherosclerosis was much higher in the deendothelialized Group A vessels than in the uninjured group B vessels. The activity of lactate dehydrogenase and of the rate-limiting glycolytic pyruvate kinase was significantly increased and the activity of lipoamide dehydrogenase decreased in the group A aortas. In the iliofemoral arteries a similar but statistically insignificant tendency was detected. There was no significant difference, however, in aortic lactate between the three groups. Thus, local hypoxia did not significantly contribute to the high degree of atherosclerosis in the group A animals in spite of the enzyme activity differences. Previous experience of the authors, using arterial microcathode pO2 measurements, indicates that following deendothelialization an adaptive proliferation of nutrient vessels and increased arterial oxygenation takes place. The average activity of the lysosomal N-acetyl-beta-glucosaminidase was five times and that of beta-glucuronidase, seven times higher in the Group A than Group B aortas; in the iliofemoral arteries the differences were even larger. The huge elevation of these hydrolases, which are involved in glycosaminoglycan catabolism, provides indirect indication that accumulation of glycosaminoglycans and possibly their ability to form complexes with apoB-containing lipoproteins played a major role in the much increased degree of atherosclerotic lesions in the Group A rabbits.
Exp Mol Pathol 1988 Apr
PMID:The effect of combined deendothelialization and hypercholesterolemia on some arterial lysosomal and glycolytic enzymes and lactate in rabbits. 335 Jan 45

The gene for lipoamide dehydrogenase (LD) has been assigned to human chromosome 7 based on filter hybridization analysis of genomic DNA from rodent-human somatic cell hybrids using a cDNA probe for human LD. No indication of multiple copies of the gene was found, in accordance with previous evidence that LD in the pyruvate, alpha-ketoglutarate, and branched chain alpha-ketoacid dehydrogenase complexes is genetically as well as biochemically identical.
Somat Cell Mol Genet 1988 Jul
PMID:Gene for lipoamide dehydrogenase maps to human chromosome 7. 339 66

In Saccharomyces cerevisiae a nuclear recessive mutation, lpd1, which simultaneously abolishes the activities of lipoamide dehydrogenase, 2-oxoglutarate dehydrogenase and pyruvate dehydrogenase has been identified. Strains carrying this mutation can grow on glucose or poorly on ethanol, but are unable to grow on media with glycerol or acetate as carbon source. The mutation does not prevent the formation of other tricarboxylic acid cycle enzymes such as fumarase, NAD+-linked isocitrate dehydrogenase or succinate-cytochrome c oxidoreductase, but these are produced at about 50%-70% of the wild-type levels. The mutation probably affects the structural gene for lipoamide dehydrogenase since the amount of this enzyme in the cell is subject to a gene dosage effect; heterozygous lpd1 diploids produce half the amount of a homozygous wild-type strain. Moreover, a yeast sequence complementing this mutation when present in the cell on a multicopy plasmid leads to marked overproduction of lipoamide dehydrogenase. Homozygous lpd1 diploids were unable to sporulate indicating that some lipoamide dehydrogenase activity is essential for sporulation to occur on acetate.
Mol Gen Genet 1986 Jul
PMID:A mutation affecting lipoamide dehydrogenase, pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase activities in Saccharomyces cerevisiae. 352 55

Transcript mapping of the Escherichia coli sucAB, aceEF and lpd genes, encoding the five components of the pyruvate and 2-oxoglutarate dehydrogenase complexes, was carried out using single-stranded M13 probes. The sucA and aceE genes encode the specific dehydrogenase components (E1o, E1p), and the sucB and aceF genes encode the specific dihydrolipoamide acyltransferases (E2o, E2p). The common lipoamide dehydrogenase (E3) component is encoded by a single lpd gene adjacent to the aceEF genes. The sucAB, aceEF and lpd genes were all expressed on independent transcripts, and the promoters and terminators were identified. In addition, readthrough transcription from the sucAB genes to a downstream gene designated sucC, and from the aceEF genes to the adjacent lpd gene, was found. The relative levels of transcription of the suc, ace and lpd genes, and of the three different transcript types covering the ace-lpd region, were quantified using RNA from cells grown on different substrates. Most of the E3 components supplying the pyruvate dehydrogenase complex appear to be synthesised from approximately 6415-base aceEF-lpd readthrough transcripts, but additional approximately 4640-base aceEF transcripts terminating after the aceF gene provide a transcriptional basis for the observed stoichiometric excess of E1p and E2p relative to E3 in the assembled complex. Conversely most of the E3 components required for the 2-oxo-glutarate dehydrogenase complex appear to be synthesised from the independent 1670-base lpd transcripts.
Mol Gen Genet 1985
PMID:Transcription analysis of the sucAB, aceEF and lpd genes of Escherichia coli. 389 91

The biochemical response of rat splenic D-T diaphorase and the histochemical distribution of the enzyme NAD(P)H-NBT reductase to the action of the polycyclic hydrocarbons benz(a)pyrene, 3-methylcholanthrene, 7,12-dimethylbenz(a)anthracene and benz(a)anthracene have been studied. The four polycyclic hydrocarbons tested in this work induced the activity of both enzymes. The stimulation of the D-T diaphorase by benz(a)pyrene is dose dependent and it is partially inhibited by dicumarol. Microsomal and mitochondrial NAD(P)H dehydrogenases are not induced by any of these compounds. The study of the histochemical distribution of the NAD(P)H-NBT reductase shows also a marked increase in the staining of the enzyme which follow a specific pattern, the cells showing the highest activity are the lymphocytes located around the marginal sinus of the white pulp and around follicular arterioles, plus red pulp lymphocytes and myeloblastic cells. The cells in the germinal center show from null to very weak activity. A correlation between the biochemical induction of the soluble D-T diaphorase of the histochemical increase of the NAD(P)H-NBT reductase is attempted.
Virchows Arch B Cell Pathol Incl Mol Pathol 1982
PMID:Rat splenic D-T diaphorase and NAD(P)H-nitroblue tetrazolium reductase. Their use to assess the action of polycyclic hydrocarbons in the lymphatic system. 613 86

The quaternary structure of the alpha-ketoglutarate dehydrogenase complex (KGDC) from Escherichia coli has been investigated by electron microscopy. 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. The analysis was greatly simplified by analyzing subcomplexes of KGDC prepared by assembly of the purified component enzymes in vitro; the subcomplexes consisted of the E2 component to which only a few E1 or E3 subunits were attached. We find that both the E1 and E3 bind on the surface of the E2 molecule approximately midway between the 4-fold and 2-fold symmetry axes of E2. There are 24 such positions per E2 molecule but, based upon the observed stoichiometries of the component enzymes, it is clear that at least half of these sites are unoccupied in KGDC. If KGDC possesses symmetry, then a mechanism must exist for selecting a symmetrically distributed subset of the potential binding sites for the E1 and E3. However, analysis of images of subcomplexes in which two E1 or E3 subunits are present suggests that binding to the E2 occurs through random selection of the potential binding sites. If native KGDC is assembled by such a mechanism, then KGDC would not have a unique quaternary structure, but instead would consist of a family of structural isomers having up to approximately 125,000 members. Consideration of independent structural and biochemical data regarding the mechanism of action of the E2 indicates that the kind of structural heterogeneity being proposed is consistent with a functional KGDC.
J Mol Biol 1983 Apr 15
PMID:alpha-Ketoglutarate dehydrogenase complex may be heterogeneous in quaternary structure. 634 9

The elucidation of the primary structure of the Escherichia coli lipoamide dehydrogenase (EC 1.8.1.4) by sequencing the corresponding structural gene (lpd) has enabled a detailed structural comparison between lipoamide dehydrogenase and the related disulphide oxido-reductase, human erythrocyte glutathione reductase (EC 1.6.4.2). Some 28% of the amino acid residues were found to be identical and a striking degree of homology was apparent throughout the polypeptide chains. It was concluded that the two enzymes possess very similar three-dimensional structures with particularly strong conservation of residues around the FAD and NAD(P) binding sites and at the redox centres of the molecules. Significant amino acid substitutions occur in the substrate binding pocket and these include an extra 18 amino acid residues at the C terminus of lipoamide dehydrogenase. Under physiological conditions, lipoamide dehydrogenase and glutathione reductase act in opposite directions, passing reducing equivalents to NAD+ or from NADPH (respectively), and two key substitutions near the redox centre could be associated with this difference in function. This study represents the first direct structural comparison between two related enzymes that are NADP+-linked (glutathione reductase) and NAD+-linked (lipoamide dehydrogenase). The differential recognition of these two cofactors could be explained in terms of amino acid substitutions. A divergent evolutionary relationship between the two enzymes including their NAD and NADP binding domains is fully supported by this analysis.
J Mol Biol 1984 Apr 15
PMID:Structural relationship between glutathione reductase and lipoamide dehydrogenase. 654 54

The FAD-containing enzyme lipoamide dehydrogenase (EC 1.6.4.3. NADH: lipoamide oxidoreductase) of Azotobacter vinelandii has been crystallized from polyethylene glycol solutions. The space group is P2(1)2(1)2(1) with one dimer in the asymmetric unit. The cell dimensions are: a = 64.2, b = 83.8, c = 193 A. X-ray reflections extend to at least 2.2 A resolution.
J Mol Biol 1983 Apr 15
PMID:Crystallization and preliminary X-ray investigation of lipoamide dehydrogenase from Azotobacter vinelandii. 668 41


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