Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:1.6.5.3 (complex I)
8,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sequence analysis of mitochondrial and nuclear candidate genes of complex I in children with deficiency of this complex and exhibiting Leigh-like syndrome has revealed, in one of them, a novel mutation in the NDUFS4 gene encoding the 18 kDa subunit. Phosphorylation of this subunit by cAMP-dependent protein kinase has previously been found to activate the complex. The present mutation consists of a homozygous G-->A transition at nucleotide position +44 of the coding sequence of the gene, resulting in the change of a tryptophan codon to a stop codon. Such mutation causes premature termination of the protein after only 14 amino acids of the putative mitochondrial targeting peptide. Fibroblast cultures from the patient exhibited severe reduction of the rotenone-sensitive NADH-->UQ oxidoreductase activity of complex I, which was insensitive to cAMP stimulation. Two-dimensional electrophoresis showed the absence of detectable normally assembled complex I in the inner mitochondrial membrane. These findings show that the expression of the NDUFS4 gene is essential for the assembly of a functional complex I.
...
PMID:A nonsense mutation in the NDUFS4 gene encoding the 18 kDa (AQDQ) subunit of complex I abolishes assembly and activity of the complex in a patient with Leigh-like syndrome. 1118 77

The globule dimensions and some electron and conformational properties of the flavoprotein (peripheral) fragment of the mitochondrial NADH dehydrogenase were determined by the time-resolved, phase-modulating, and polarization fluorescence spectroscopies, as well as correlated confocal microscopy. The rotational and the diffusion (translocation) diameters of the protein fragment were shown to be no less than 44 A and approximately 72 A, respectively. The diameter of protomitochondrial particles from the bovine heart, which were used for the isolation of the fraction of peripheral fragments, was no less than 2300 A. The fluorescence from tryptophan and flavin fluorophores in the fragment is strongly quenched by iron of the iron-sulfur clusters, which suggests that a strong electron-vibrational interaction of iron with Trp residues and flavin takes place. An overlapping of the electron clouds of iron-sulfur clusters, Trp residues, and flavin is likely to facilitate the electron transfer through the protein. The heat inactivation of the enzyme was accompanied by neither its substantial conformational changes, nor a considerable release of iron ions from the clusters located near the Trp residues.
...
PMID:[The globule diameter and various electron and conformational properties of the flavoprotein fragment of mitochondrial NADH dehydrogenase studied by fluorescence spectroscopy]. 1122 Dec 52

Mitochondrial respiratory function was studied in permeabilized pig liver biopsies. The cell membrane was permeabilized mechanically in tissue samples of 2-7 mg, for application of a standardized substrate/inhibitor titration protocol in high-resolution respirometry. Specific respirometric tests demonstrated complete plasma membrane permeabilization and accessibility of substrates to intact mitochondria. High respiratory adenylate control ratios and cytochrome c conservation in the tissue preparation were comparable or even better than in isolated mitochondria. Citrate synthase and cytochrome c oxidase activities remained at 85% of controls after up to 98 h storage of liver tissue at 0 degrees C in histidine-tryptophan-ketoglutarate solution. Multiple mitochondrial defects, however, were indicated after 48 h cold storage by the decline in respiratory capacity, which was lowered to a larger extent with complex I substrates compared to respiration with substrates for complex II or IV, measured in the absence of cytochrome c. After prolonged ischemia, the adenylate control ratio was significantly reduced, and cytochrome c depletion was detected by the stimulatory effect of cytochrome c. High-resolution respirometry allows the assessment of mitochondrial function in a few milligrams of permeabilized liver tissue, without isolation of mitochondria. This provides a basis for the analysis of mitochondrial function in human liver biopsies.
...
PMID:Evaluation of mitochondrial respiratory function in small biopsies of liver. 1205 47

Phylogenetic relationships of a subset of Aphanius fish comprising central Anatolia, Turkey, are investigated to test the hypothesis of geographic speciation driven by early Pliocene orogenic events in spite of morphological similarity. We use 3434 aligned base pairs of mitochondrial DNA from 42 samples representing 36 populations of three species and six outgroup species to test this hypothesis. Genes analyzed include those encoding the 12S and 16S ribosomal RNAs; transfer RNAs coding for valine, leucine, isoleucine, glutamine, methionine, tryptophan, alanine, asparagine, cysteine, and tyrosine; and complete NADH dehydrogenase subunits I and II. Distance based minimum evolution and maximum-likelihood analyses identify six well-supported clades consisting of Aphanius danfordii, Aphanius sp. aff danfordii, and four clades of Aphanius anatoliae. Parsimony analysis results in 462 equally parsimonious trees, all of which contain the six well supported clades identified in the other analyses. Our phylogenetic results are supported by hybridization studies (Villwock, 1964), and by the geological history of Anatolia. Phylogenetic relationships among the six clades are only weakly supported, however, and differ among analytical methods. We therefore test and subsequently reject the hypothesis of simultaneous diversification among the six central Anatolian clades. However, our analyses do not identify any internodes that are significantly better supported than expected by chance alone. Therefore, although bifurcating branching order is hypothesized to underlie this radiation, the exact branching order is difficult to estimate with confidence.
...
PMID:Molecular phylogeny and historical biogeography of the Aphanius (Pisces, Cyprinodontiformes) species complex of central Anatolia, Turkey. 1238 56

We examined the distribution of N-formylkynurenine, a product of the dioxidation of tryptophan residues in proteins, throughout the human heart mitochondrial proteome. This oxidized amino acid is associated with a distinct subset of proteins, including an over-representation of complex I subunits as well as complex V subunits and enzymes involved in redox metabolism. No relationship was observed between the tryptophan modification and methionine oxidation, a known artifact of sample handling. As the mitochondria were isolated from normal human heart tissue and not subject to any artificially induced oxidative stress, we suggest that the susceptible tryptophan residues in this group of proteins are "hot spots" for oxidation in close proximity to a source of reactive oxygen species in respiring mitochondria.
...
PMID:Oxidative post-translational modification of tryptophan residues in cardiac mitochondrial proteins. 1267 31

There is growing evidence that oxidative phosphorylation (OXPHOS) generates reactive oxygen and nitrogen species within mitochondria as unwanted byproducts that can damage OXPHOS enzymes with subsequent enhancement of free radical production. The accumulation of this oxidative damage to mitochondria in brain is thought to lead to neuronal cell death resulting in neurodegeneration. The predominant reactive nitrogen species in mitochondria are nitric oxide and peroxynitrite. Here we show that peroxynitrite reacts with mitochondrial membranes from bovine heart to significantly inhibit the activities of complexes I, II, and V (50-80%) but with less effect upon complex IV and no significant inhibition of complex III. Because inhibition of complex I activity has been a reported feature of Parkinson's disease, we undertook a detailed analysis of peroxynitrite-induced modifications to proteins from an enriched complex I preparation. Immunological and mass spectrometric approaches coupled with two-dimensional PAGE have been used to show that peroxynitrite modification resulting in a 3-nitrotyrosine signature is predominantly associated with the complex I subunits, 49-kDa subunit (NDUFS2), TYKY (NDUFS8), B17.2 (17.2-kDa differentiation associated protein), B15 (NDUFB4), and B14 (NDUFA6). Nitration sites and estimates of modification yields were deduced from MS/MS fragmentograms and extracted ion chromatograms, respectively, for the last three of these subunits as well as for two co-purifying proteins, the beta and the d subunits of the F1F0-ATP synthase. Subunits B15 (NDUFB4) and B14 (NDUFA6) contained the highest degree of nitration. The most reactive site in subunit B14 was Tyr122, while the most reactive region in B15 contained 3 closely spaced tyrosines Tyr46, Tyr50, and Tyr51. In addition, a site of oxidation of tryptophan was detected in subunit B17.2 adding to the number of post-translationally modified tryptophans we have detected in complex I subunits (Taylor, S. W., Fahy, E., Murray, J., Capaldi, R. A., and Ghosh, S. S. (2003) J. Biol. Chem. 278, 19587-19590). These sites of oxidation and nitration may be useful biomarkers for assessing oxidative stress in neurodegenerative disorders.
...
PMID:Oxidative damage to mitochondrial complex I due to peroxynitrite: identification of reactive tyrosines by mass spectrometry. 1285 34

Melatonin, or N-acetyl-5-methoxytryptamine, is a compound derived from tryptophan that is found in all organisms from unicells to vertebrates. This indoleamine may act as a protective agent in disease conditions such as Parkinson's, Alzheimer's, aging, sepsis and other disorders including ischemia/reperfusion. In addition, melatonin has been proposed as a drug for the treatment of cancer. These disorders have in common a dysfunction of the apoptotic program. Thus, while defects which reduce apoptotic processes can exaggerate cancer, neurodegenerative disorders and ischemic conditions are made worse by enhanced apoptosis. The mechanism by which melatonin controls cell death is not entirely known. Recently, mitochondria, which are implicated in the intrinsic pathway of apoptosis, have been identified as a target for melatonin actions. It is known that melatonin scavenges oxygen and nitrogen-based reactants generated in mitochondria. This limits the loss of the intramitochondrial glutathione and lowers mitochondrial protein damage, improving electron transport chain (ETC) activity and reducing mtDNA damage. Melatonin also increases the activity of the complex I and complex IV of the ETC, thereby improving mitochondrial respiration and increasing ATP synthesis under normal and stressful conditions. These effects reflect the ability of melatonin to reduce the harmful reduction in the mitochondrial membrane potential that may trigger mitochondrial transition pore (MTP) opening and the apoptotic cascade. In addition, a reported direct action of melatonin in the control of currents through the MTP opens a new perspective in the understanding of the regulation of apoptotic cell death by the indoleamine.
...
PMID:Melatonin mitigates mitochondrial malfunction. 1561 31

The total nucleotide sequence of the mitochondrial genome of the yeast Kluyveromyces lactis was determined. The DNA is a circular molecule of 40,291 base pairs, with 26.1% GC. It contains a set of protein- and RNA-coding genes equivalent to those of the Saccharomyces cerevisiae mitochondrial genome. The genome size is about one half of that of S. cerevisiae mitochondrial DNA. The difference in size is due essentially to a reduced proportion of intergenic and intronic sequences. The coding sequences occupy about one third of the genome, the rest being composed of AT-rich sequences and numerous short GC-rich clusters that are dispersed mostly in the non-coding regions and a few within coding sequences. The presence of these GC clusters is a characteristic feature common to K. lactis and S. cerevisiae mitochondrial DNA, although their sequence patterns are different. The absence of the NADH dehydrogenase subunit genes distinguishes this yeast and S. cerevisiae from the typically aerobic species. The genetic code appears to be that of the standard fungal mitochondrial genomes, with UGA as a tryptophan codon. There are only 22 transfer RNA genes, those corresponding to CUN and CGN codons being missing. CUN codons are absent in the protein-coding sequences. There are five CGN codons within the open reading frames, but they are located exclusively in the introns, rendering them untranslatable. Introns are found only the genes in KlCOX1 and LrRNA. The transcription promoter motif known in S. cerevisiae and several other yeast species is also present. All genes are transcribed from the same strand, except those on a single 7-kilobase pairs segment (EMBL Accession No. AY654900).
...
PMID:Complete nucleotide sequence of the mitochondrial DNA from Kluyveromyces lactis. 1569 36

Melatonin, originally discovered as a hormone of the pineal gland, is also produced in other organs and represents, additionally, a normal food constituent found in yeast and plant material, which can influence the level in the circulation. Compared to the pineal, the gastrointestinal tract contains several hundred times more melatonin, which can be released into the blood in response to food intake and stimuli by nutrients, especially tryptophan. Apart from its use as a commercial food additive, supraphysiological doses have been applied in medical trials and pure preparations are well tolerated by patients. Owing to its amphiphilicity, melatonin can enter any body fluid, cell or cell compartment. Its properties as an antioxidant agent are based on several, highly diverse effects. Apart from direct radical scavenging, it plays a role in upregulation of antioxidant and downregulation of prooxidant enzymes, and damage by free radicals can be reduced by its antiexcitatory actions, and presumably by contributions to appropriate internal circadian phasing, and by its improvement of mitochondrial metabolism, in terms of avoiding electron leakage and enhancing complex I and complex IV activities. Melatonin was shown to potentiate effects of other antioxidants, such as ascorbate and Trolox. Under physiological conditions, direct radical scavenging may only contribute to a minor extent to overall radical detoxification, although melatonin can eliminate several of them in scavenger cascades and potentiates the efficacy of antioxidant vitamins. Melatonin oxidation seems rather important for the production of other biologically active metabolites such as N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), which have been shown to also dispose of protective properties. Thus, melatonin may be regarded as a prodrug, too. AMK interacts with reactive oxygen and nitrogen species, conveys protection to mitochondria, inhibits and downregulates cyclooxygenase 2.
...
PMID:Melatonin, a potent agent in antioxidative defense: actions as a natural food constituent, gastrointestinal factor, drug and prodrug. 1615 6

Phylogenetic relationships of members of the subfamily Poeciliinae (Cyprinodontiformes) are investigated to test alternate hypotheses of diversification resulting from the assembly of the Central America and the Caribbean from the Cretaceous period onwards. We use 4333 aligned base pairs of mitochondrial DNA and 1549 aligned base pairs of nuclear DNA from 55 samples representing 48 ingroup and seven outgroup species to test this hypothesis. Mitochondrial genes analyzed include those encoding the 12S and 16S ribosomal RNAs; transfer RNAs coding for valine, leucine, isoleucine, glutamine, methionine, tryptophan, alanine, asparagine, cysteine and tyrosine; and complete cytochrome b and NADH dehydrogenase subunit I and II; nuclear gene analyzed included the third exon of the recombination activation gene 1 (RAG1). Analyses of combined mtDNA and nuclear DNA data sets result in a well-supported phylogenetic hypothesis. This hypothesis is in conflict with the classical taxonomic assignment of genera into tribes and phylogenetic hypotheses based on the taxonomy; however, the molecular hypothesis defines nine clades that are geographically restricted and consistent with the geological evolution of Central America and the Caribbean. Our analyses support multiple colonization events of Middle America followed by a mix of vicariance and dispersal events.
...
PMID:A phylogenetic and biogeographic perspective on the evolution of poeciliid fishes. 1718 5


<< Previous 1 2 3 4 Next >>

---