Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.8.1.4 (diaphorase)
 2,754 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

A sample of colonies from the Clarke-Carbon ColE1-Escherichia coli DNA plasmid gene bank was screened by conjugation for complementation of the lipoamide dehydrogenase lesion of a deletion strain lacking all components of the pyruvate dehydrogenase complex, delta (aroP aceE aceF lpd). Two ColE1-lpd+ hybrid plasmids were identified: pGS2 (ColE1-ace lpd+; 24 kb) and pGS5 (ColE1-lpd+; 14 kb). Enzymological studies confirmed that pGS2 expressed all the activities of the pyruvate dehydrogenase complex, whereas pGS5 expressed the lipoamide dehydrogenase and acetyltransferase activities (the latter from a ColE1 promoter). These and other plasmids were used to construct a 47-site (15 enzymes) restriction map for a 24.2 kb segment of bacterial DNA in the nadC-lpd region. A further 13 sites (six enzymes) were defined in a 5.4 kb sub-segment containing the lpd gene. lambda phage derivatives containing specific fragments were constructed and used in transduction studies which located the ace and lpd genes in a 7.78 kb sub-segment flanked by AccI and NruI sites.
J Gen Microbiol 1983 Mar
PMID:Hybrid plasmids containing the pyruvate dehydrogenase complex genes and gene-DNA relationships in the 2 to 3 minute region of the Escherichia coli chromosome. 630 28

The three components of the pyruvate dehydrogenase complex of Escherichia coli are encoded by three linked genes, ace E (pyruvate dehydrogenase, E1), aceF (dihydrolipoamide acetyltransferase, E2) and lpd (lipoamide dehydrogenase, E3, situated close to the nadC (quinolinate phosphoribosyltransferase) and aroP (general aromatic amino acid permease) genes with the gene order: nadC-aroP-aceE-aceF-lpd. Several types of transducing phages, lambda nadC and lambda lpd, carrying the nadC and lpd genes were isolated from populations of artificially constructed transducing phages containing R.HindIII or R.EcoRI fragments of bacterial DNA, by selecting for their ability to complement the metabolic lesions of the corresponding mutants. The cloned fragments were extended to include a functional ace operon by in vivo methods involving prophage insertion into the nadC-lpd region and aberrant excision to yield lambda nadC-lpd and lambda lpd-ace phages. These contained overlapping segments of bacterial DNA capable of expressing the aceE, aceF and lpd genes. A physical map of a 20 kilobase pairs (kb) segment of bacterial DNA encoding the entire nadC-lpd region, bounded by R.HindIII and R.EcoRI targets and possessing several internal restriction targets, R.HindIII (3) and R.EcoRI (2), was constructed. Using a combination of nutritional and enzymological studies with dilysogens and genetic analysis with ace mutants the approximate positions of the genes specifying the pyruvate dehydrogenase complex were traced to a 9.5 kb segment of the restriction map. The cloned lpd gene was expressed in the complete absence of a functional ace operon and when the major lambda promoters were repressed. This confirms that the lpd gene can be independently transcribed from its own promoter.
J Gen Microbiol 1980 Dec
PMID:Molecular cloning of the pyruvate dehydrogenase complex genes of Escherichia coli. 645 99

Four independent ace mutants of Pseudomonas aeruginosa PAO lacking the activity of the pyruvate dehydrogenase complex have been isolated. They resembled ace mutants of Escherichia coli and Salmonella typhimurium in requiring acetate as an essential supplement for aerobic growth on glucose, succinate or lactate and in their ability to utilize acetate as sole carbon and energy source. Assays for the individual components of the pyruvate dehydrogenase complex indicated that they lacked the pyruvate dehydrogenase component (El) or the pyruvate dehydrogenase and dihydrolipoamide acetyltransferase components (E1 and E2) but not the lipoamide dehydrogenase component (E3). Genetic studies with plasmid R68.45-mediated conjugation and phage F116L-mediated transduction indicated that the ace mutations are located at approximately 15 min in the P. aeruginosa PAO linkage map.
J Gen Microbiol 1980 Oct
PMID:Isolation and properties of pyruvate dehydrogenase complex mutants of Pseudomonas aeruginosa PAO. 678 85

The pyruvate dehydrogenase complex of Pseudomonas aeruginosa PAO was purified by affinity chromatography on ethanol-Sepharose 2B followed by sucrose density gradient centrifugation. The overall purification was 130-fold based on enzyme activity. The purified complex contained three major and one minor polypeptide components when analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. These were identified by heat treatment, limited proteolysis and peptide mapping as pyruvate dehydrogenase (El; Mr 92500), acetyltransferases (E2; major component, Mr 76000, and minor component, Mr 77800) and lipoamide dehydrogenase (E3; Mr 58000). The purified complex had a sedimentation coefficient of 48S and the specific activity for the overall reaction of the complex was 6.5 micromol substrate transformed (mg protein)-1 min-1 at the optimum pH (7.8) and 25 degrees C. The lesions in four ace mutants lacking overall pyruvate dehydrogenase complex activity were identified after partial purification of the corresponding cell-free extracts. Three strains, designated ace A mutants, lacked pyruvate dehydrogenase activity (E1 component) and one strain, and ace B mutant, lacked the activity of the acetyltransferase (E2 component).
J Gen Microbiol 1980 Oct
PMID:The pyruvate dehydrogenase complex of Pseudomonas aeruginosa PAO Purification, properties and characterization of mutants. 678 86

Epidemiological and anatomical studies support the theory that disturbances of brain development may play a contributory role in the etiology of schizophrenia. Anatomical findings suggest that the normal pattern of neuronal migration during development of the cerebral cortex may be affected in the brains of schizophrenics, with the implication that cortical connectivity and associative function will be disrupted. In the present investigation in matched schizophrenic and control brains, we examined a particular population of neurons found in the prefrontal cortex and underlying white matter and characterized by histochemical staining for the enzyme nicotinamide-adenine dinucleotide phosphate-diaphorase. In normal brains, these neurons are found in highest numbers in the white matter immediately deep to layer VI of the cortex where they remain from the subplate, an early formed, but transitory structure that plays a key role in cortical development and connection formation. The dorsolateral prefrontal area of schizophrenics showed a significant decline in nicotinamide-adenine dinucleotide phosphate-diaphorase neurons in the superficial white matter and in the overlying cortex but a significant increase in these neurons in white matter deeper than 3 mm from the cortex. These findings are consistent with a disturbance of the subplate during development in which the normal pattern of programmed cell death is compromised and accompanied by a defect in the normal orderly migration of neurons toward the cortical plate. These are likely to have serious consequences for the establishment of a normal pattern of cortical connections leading to a potential breakdown of frontal lobe function in schizophrenics.
Arch Gen Psychiatry 1993 Mar
PMID:Altered distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase cells in frontal lobe of schizophrenics implies disturbances of cortical development. 767 91

The distribution of neurons expressing the enzyme nicotinamide-adenine dinucleotide phosphate-diaphorase (NADPH-d) in the lateral and medial temporal lobes of schizophrenic and matched control brains was investigated in a systematic blind analysis. Schizophrenics had significantly lower numbers of NADPH-d neurons in the hippocampal formation and in the neocortex of the lateral temporal lobe but significantly greater numbers of NADPH-d neurons in the white matter of the lateral temporal lobe and a tendency toward greater numbers in parts of the parahippocampal white matter. The distorted distribution of NADPH-d neurons in the lateral temporal lobe, which may be explained by developmental disturbances, such as impaired neuronal migration or an alteration in the death cycle of transitory subcortical neurons, is similar to that found in the prefrontal cortex of schizophrenics. Alterations of cortical ontogenesis, as reflected in the distribution of NADPH-d neurons, appear to be widespread among neocortical association fields in schizophrenics and may provide a clue to the cause of the disease.
Arch Gen Psychiatry 1993 Mar
PMID:Distorted distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase neurons in temporal lobe of schizophrenics implies anomalous cortical development. 767 92

The presence of several NADH dehydrogenase activities associated with cytoplasmic membrane vesicles of chemoheterotrophically grown Rhodobacter capsulatus MT1131 was demonstrated by combining isoelectric focusing with NADH-tetranitrobluetetrazolium activity staining, a procedure that should have general applicability in the analysis of bacterial NADH dehydrogenase activities. Low pI (pI = 5.7), Mid pI (pI = 6.9) and High pI (pI = 8.5) bands were resolved. The Mid pI NADH dehydrogenase activity was purified and identified as a dihydrolipoyl dehydrogenase. Our data indicate that this dihydrolipoyl dehydrogenase is derived from a 2-oxoacid dehydrogenase complex which is associated with the cytoplasmic membrane.
J Gen Microbiol 1993 Aug
PMID:Membrane-associated NADH dehydrogenase activities in Rhodobacter capsulatus: purification of a dihydrolipoyl dehydrogenase. 840 25

Nitrate reductase from the yeast Candida nitratophila was found to contain one molecule of cytochrome b557 and one atom of molybdenum per subunit. FAD/haem-dependent diaphorase activity (haem domain) was associated with a 40 kDa tryptic fragment of the subunit. The 50 amino-terminal residues of this fragment were determined, and the sequence did not show significant similarity to deduced sequences of other nitrate reductases previously published. Increasing ionic strength in vitro had a stimulatory effect on enzymic activity via stimulation of the molybdenum-dependent terminal nitrate-reducing activity. Stimulation of activity by exogenous protein (bovine serum albumin or casein) also appeared to be an ionic effect. Stimulation of catalytic activity by phosphate was a separate effect.
J Gen Microbiol 1993 Mar
PMID:Further characterization of the assimilatory nitrate reductase from the yeast Candida nitratophila. 847 56

1. Lipoic acid is an example of an existing drug whose therapeutic effect has been related to its antioxidant activity. 2. Antioxidant activity is a relative concept: it depends on the kind of oxidative stress and the kind of oxidizable substrate (e.g., DNA, lipid, protein). 3. In vitro, the final antioxidant activity of lipoic acid is determined by its concentration and by its antioxidant properties. Four antioxidant properties of lipoic acid have been studied: its metal chelating capacity, its ability to scavenge reactive oxygen species (ROS), its ability to regenerate endogenous antioxidants and its ability to repair oxidative damage. 4. Dihydrolipoic acid (DHLA), formed by reduction of lipoic acid, has more antioxidant properties than does lipoic acid. Both DHLA and lipoic acid have metal-chelating capacity and scavenge ROS, whereas only DHLA is able to regenerate endogenous antioxidants and to repair oxidative damage. 5. As a metal chelator, lipoic acid was shown to provide antioxidant activity by chelating Fe2+ and Cu2+; DHLA can do so by chelating Cd2+. 6. As scavengers of ROS, lipoic acid and DHLA display antioxidant activity in most experiments, whereas, in particular cases, pro-oxidant activity has been observed. However, lipoic acid can act as an antioxidant against the pro-oxidant activity produced by DHLA. 7. DHLA has the capacity to regenerate the endogenous antioxidants vitamin E, vitamin C and glutathione. 8. DHLA can provide peptide methionine sulfoxide reductase with reducing equivalents. This enhances the repair of oxidatively damaged proteins such as alpha-1 antiprotease. 9. Through the lipoamide dehydrogenase-dependent reduction of lipoic acid, the cell can draw on its NADH pool for antioxidant activity additionally to its NADPH pool, which is usually consumed during oxidative stress. 10. Within drug-related antioxidant pharmacology, lipoic acid is a model compound that enhances understanding of the mode of action of antioxidants in drug therapy.
Gen Pharmacol 1997 Sep
PMID:The pharmacology of the antioxidant lipoic acid. 937 35


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