Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.5.3 (complex I)
 8,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Light absorption, fluorescence and linear dichroism (l.d.) spectroscopy and fluorescence lifetime measurements reveal characteristic differences that arise from structural differences between the DNA complexes with the optical enantiomers (+)- and (-)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxides (BPDE), a strong and a weak carcinogen, respectively. Both types of complexes appear heterogeneous but can be described as composed of two major complex types I and II, in different proportions. Like previously observed for DNA modified by racemic anti-BPDE, the only distinguishable spectral component of (+)-anti-BPDE-DNA is the type II complex, whereas the (-)-anti-BPDE-DNA is a mixture of both types I and II complexes. The type I complex is characterized by negative I.d., a light absorption and excitation spectrum maximum (above 300 nm) at 354 nm and strong fluorescence quenching in native DNA, properties expected for an intercalation complex in the classical sense. The type II complex on the other hand is characterized by positive I.d., a light absorption and excitation spectrum maximum (above 300 nm) at 345 nm, and moderate fluorescence quenching in native DNA, properties not consistent with intercalation geometry. Rather, the BPDE chromophore forms less than 55 degree angle with the mean direction of the helix axis. Its interaction with the DNA bases seems to be less than in complex I, and is highly sensitive to Ag+ ions. The type II complex may be associated with local obstruction of base-pairing properties of native DNA. Since DNA-binding of chemical carcinogens is considered crucial for tumour initiation it follows that the unique properties of the type II BPDE-DNA complex may be of fundamental importance in benzo[a]pyrene carcinogenesis.
Carcinogenesis 1984 Sep
PMID:Spectroscopic studies of DNA complexes formed after reaction with anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-oxide enantiomers of different carcinogenic potency. 643 55

We report the case of an infant with hypoglycemia, progressive lactic acidosis, an increased serum lactate/pyruvate ratio, and elevated plasma alanine, who had a moderate to profound decrease in the ability of mitochondria from four organs to oxidize pyruvate, malate plus glutamate, citrate, and other NAD+-linked respiratory substrates. The capacity to oxidize the flavin adenine dinucleotide-linked substrate, succinate, was normal. The most pronounced deficiency was in skeletal muscle, the least in kidney mitochondria. Enzymatic assays on isolated mitochondria ruled out defects in complexes II, III, and IV of the respiratory chain. Further studies showed that the defect was localized in the inner membrane mitochondrial NADH-ubiquinone oxidoreductase (complex I). When ferricyanide was used as an artificial electron acceptor, complex I activity was normal, indicating that electrons from NADH could reduce the flavin mononucleotide cofactor. However, electron paramagnetic resonance spectroscopy performed on liver submitochondrial particles showed an almost total loss of the iron-sulfur clusters characteristic of complex I, whereas normal signals were noted for other mitochondrial iron-sulfur clusters. This infant is presented as the first reported case of congenital lactic acidosis caused by a deficiency of the iron-sulfur clusters of complex I of the mitochondrial electron transport chain.
J Clin Invest 1984 Sep
PMID:Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis. 643 47

Analysis by crossed-immunoelectrophoresis of Paracoccus denitrificans membrane vesicles has shown that only one antigen stains for NADH dehydrogenase activity. This activity could be partially purified by a combination of gel filtration and ion-exchange chromatography of membrane vesicles that had been solubilised in the non-ionic detergent Nonidet P-40. From the limited number of precipitates observed after crossed immunoelectrophoresis of this partially purified preparation of NADH dehydrogenase it was possible to excise specifically part of the precipitate that stained for NADH dehydrogenase. Excised precipitates containing NADH dehydrogenase that had been radiolabelled by growth of cells in the presence of [35S]SO2-(4) allowed the polypeptide composition of the enzyme to be determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate followed by fluorography. Two subunits were identified with estimated relative molecular masses of 48000 and 25000. Subunits of similar molecular weight are found in the flavoprotein fragment of the NADH dehydrogenase of the mammalian mitochondrial respiratory chain. The latter has general similarities with the respiratory chain in the plasma membrane of P. denitrificans.
Eur J Biochem 1984 Sep 17
PMID:Immunochemical identification of a two-subunit NADH-ubiquinone oxidoreductase from Paracoccus denitrificans. 643 8

Pea leaf mitochondria showed complex kinetics for malate metabolism. O2 uptake increased as malate concentration increased from 0 to 10 mM, reached a plateau between 10 and 20 mM malate, and then increased again up to 40 mM malate. Analysis of the products of malate oxidation by high-performance liquid chromatography revealed that the first phase of O2 uptake coincided with the synthesis of both pyruvate and oxalacetate (OAA) while the second phase of O2 uptake at higher malate levels usually occurred with a large increase in OAA formation. The biphasic response in O2 uptake and the changing ratios of pyruvate and OAA synthesis did not appear to be the direct result of the differing Km values of malate dehydrogenase and malic enzyme. Rather, they resulted from thermodynamic properties of these two malate oxidases and the kinetics of the two NADH dehydrogenases found in plant mitochondria. At low malate concentrations the rotenone-sensitive NADH dehydrogenase was active and could accept electrons from both malate oxidases. This NADH dehydrogenase became saturated at about 10 mM malate. At higher malate concentrations the rotenone-insensitive NADH dehydrogenase was increasingly important and its increased electron transport capacity was best exploited by malate dehydrogenase. At the higher malate concentrations an increasing portion of the electrons from malate reduce O2 through the alternative oxidase. Although this coincided with the second phase of malate-dependent O2 uptake it was not required for this phase to be seen.
Arch Biochem Biophys 1983 Sep
PMID:Changes in the electron transport chain of pea leaf mitochondria metabolizing malate. 662 11

We show that six mapped recessive lethal point mutations of the Notch locus affect mitochondrial enzyme activities: NADH oxidase, NADH dehydrogenase, succinate dehydrogenase and alpha-glycerophosphate dehydrogenase. The mutant N264-40, which has the same morphological and embryological effects as the Notch8 deletion, demonstrates the same biochemical effects and dosage relations as Notch8. The other five mapped recessive lethals also affect four enzymic activities. They show specific patterns of activity that depend in several cases on the wild-type chromosome in the heterozygous females. That effect occurs with mutants located in the extreme right part of the Notch locus where some mutations, according to other authors, show temperature-sensitive expression.
Genetics 1981 Sep
PMID:The action of the notchlocus in Drosophila melanogaster. II. Biochemical effects of recessive lethals on mitochondrial enzymes. 680 3

We describe two patients with mitochondrial myopathies who presented with complex multisystem diseases predominantly affecting the central nervous system. In both cases the disease ran a fluctuating clinical course, eventually leading to profound impairment of intellectual function. In Case 1 dementia was associated with optic atrophy, absent pupillary responses, impaired eye movements and generalized dystonic rigidity without evidence of weakness or loss of muscle bulk. In Case 2 myoclonus preceded the onset of ataxia, generalized weakness and mental confusion by several years. Biochemical studies on isolated muscle mitochondria revealed defects in the mitochondrial respiratory chain which were located at NADH-CoQ reductase in Case 1, and at cytochrome b in Case 2. This study illustrates the potential value of muscle biopsy in the diagnosis of unusual and otherwise unexplained cerebral syndromes in man, even in the absence of muscle weakness.
Brain 1982 Sep
PMID:Mitochondrial encephalomyopathies: biochemical studies in two cases revealing defects in the respiratory chain. 710 66

The Ca(2+)-independent form of nitric oxide synthase was induced in rat neonatal astrocytes in primary culture by incubation with lipopolysaccharide (1 microgram/ml) plus interferon-gamma (100 U/ml), and the activities of the mitochondrial respiratory chain components were assessed. Incubation for 18 h produced 25% inhibition of cytochrome c oxidase activity. NADH-ubiquinone-1 reductase (complex I) and succinate-cytochrome c reductase (complex II-III) activities were not affected. Prolonged incubation for 36 h gave rise to a 56% reduction of cytochrome c oxidase activity and a 35% reduction in succinate-cytochrome c reductase activity, but NADH-ubiquinone-1 reductase activity was unchanged. Citrate synthase activity was not affected by any of these conditions. The inhibition of the activities of these mitochondrial respiratory chain complexes was prevented by incubation in the presence of the specific nitric oxide synthase inhibitor NG-monomethyl-L-arginine. The lipopolysaccharide/interferon-gamma treatment of the astrocytes produced an increase in glycolysis and lactate formation. These results suggest that inhibition of the mitochondrial respiratory chain after induction of astrocytic nitric oxide synthase may represent a mechanism for nitric oxide-mediated neurotoxicity.
J Neurochem 1994 Sep
PMID:Nitric oxide-mediated inhibition of the mitochondrial respiratory chain in cultured astrocytes. 751 65

The genes encoding the NADH dehydrogenase subunits of respiratory complex I have not been identified so far in the mitochondrial DNA (mtDNA) of yeasts. In the linear mtDNA of Candida parapsilosis, we found six new open reading frames whose sequences were unambiguously homologous to those of the genes known to code for NADH dehydrogenase subunit proteins of different organisms, i.e., ND1, ND2, ND3, ND4L, ND5, and ND6. The gene for ND4 also appears to be present, as judged from hybridization experiments with a Podospora gene probe. Specific transcripts from these open reading frames (ND genes) could be detected in the mitochondria. Hybridization experiments using C. parapsilosis genes as probes suggested that ND genes are present in the mtDNAs of a wide range of yeast species including Candida catenulata, Pichia guilliermondii, Clavispora lusitaniae, Debaryomyces hansenii, Hansenula polymorpha, and others.
J Bacteriol 1994 Sep
PMID:NADH dehydrogenase subunit genes in the mitochondrial DNA of yeasts. 752 69

The status of glutathione (GSH) and protein thiol homeostasis was examined in rat brain regions during reperfusion after moderate and severe cerebral ischemia. GSH levels were decreased in brain regions during reperfusion for 1 hr after moderate or severe ischemia for 0.5 hr. Maximal loss of GSH (50-66%) was observed in the striatum and hippocampus. The GSH lost from the brain regions was essentially recovered as protein-glutathione mixed disulfide (PrSSG) with concomitant loss of protein thiols (PrSH). The activities of enzymes such as Na+K+ ATPase, NADH dehydrogenase and glutathione reductase were also inhibited but were restored after incubation of the brain homogenate with dithiothreitol. The depletion of GSH was also accompanied by an increase in the levels of malondialdehyde and reactive oxygen species. The total GSH recovered as sum of GSH and PrSSG was significantly higher than the sham-operated controls in the hippocampus and striatum after 1 hr of reperfusion, after moderate ischemia for 0.5 hr, and at the end of 24 hr of reperfusion the GSH-protein thiol homeostasis was restored. In contrast after 1 hr of reperfusion after severe ischemia, the GSH recovered as sum of GSH and PrSSG was not significantly different from sham-operated controls and at the end of 24 hr, 7 of 9 animals died. The recuperation of the brain from oxidative stress during reperfusion after moderate ischemia was thus preceded by increased recovery of total GSH essentially in the form of PrSSG. Thus, rapid restoration of thiol homeostasis in the brain during reperfusion may help the brain recover from reperfusion injury.
J Pharmacol Exp Ther 1995 Sep
PMID:Glutathione and protein thiol homeostasis in brain during reperfusion after cerebral ischemia. 756 84

The rate of transfer of reducing equivalents from cytoplasm to mitochondria has been examined in Ehrlich ascites tumour cells incubated in the presence of lactate. The flux of reducing equivalents was determined from the rate of metabolism of reduced intermediates that are oxidized within the cytosol. The magnitude of the flux of reducing equivalents was dependent on both the concentration of added lactate and the presence of carbohydrate. The rate of flux was twice as great in the presence of glucose and four times as high when glucose and lactate were added together as when lactate was the only added substrate. Fructose was less effective than glucose in stimulating reducing equivalent flux. In the presence of glucose or fructose, there was a substantial accumulation of hexose phosphates, dihydroxyacetone phosphate and glycerol 3-phosphate. Rotenone, an inhibitor of NADH dehydrogenase, and amino-oxyacetate, which inhibits the malate/aspartate shuttle, were powerful suppressors of reducing equivalent flux from lactate as sole substrate, but were much less potent in the presence of carbohydrate. Antimycin substantially inhibited reducing equivalent flux from all combinations of added substrates, consistent with its ability to block oxidation of reducing equivalents transferred by both the malate/aspartate and glycerol 3-phosphate shuttles. The glycerol 3-phosphate shuttle represents around 80% of the maximum total observed activity but is active only while glycolytic intermediates are present to provide the necessary substrates of the shuttle. This Ehrlich ascites cell line has an essentially similar total reducing equivalent shuttle capacity to that of isolated hepatocytes.
Biochem J 1995 Sep 01
PMID:Substrate-dependent utilization of the glycerol 3-phosphate or malate/aspartate redox shuttles by Ehrlich ascites cells. 765 9


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