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)

The effect of surangin B, an insecticidal natural product coumarin, on presynaptic release of endogenous amino acids was investigated using a purified synaptosomal fraction isolated from mouse brain. Surangin B stimulated the release of glutamic acid (GLU), gamma-aminobutyric acid (GABA), serine, alanine and the aminosulfonic acid taurine from synaptosomes at micromolar concentrations. In all cases, these responses were reduced by removing calcium from the saline and surangin B-evoked release of GLU, GABA, aspartic acid (ASP) and alanine was significantly inhibited by the sodium channel blocker tetrodotoxin. Rotenone (a complex I inhibitor) and carbonyl cyanide chlorophenylhydrazone (CCCP; an uncoupler), were more potent releasers of amino acids from synaptosomes than surangin B, however, carboxin (a complex II-selective inhibitor), was extremely weak to ineffective in this regard. The stimulatory effect of surangin B and complex III-selective inhibitors on release of GLU, GABA, ASP and alanine by synaptosomes was significantly reduced by N,N,N',N'-tetramethyl-p-phenylenediamine, suggesting that blockade of complex III in intraterminal mitochondria is an important effect of this coumarin. Our results demonstrate that surangin B, in common with CCCP and inhibitors of complex I and III, cause release of both neurotransmitter and non-neurotransmitter amino acids from nerve endings in vitro. However, in contrast to most classical agents which interfere selectively with mitochondrial function, the release of endogenous amino acids from synaptosomes by surangin B also involves a moderate extracellular calcium ion-dependent component and relies partially on sodium ion entry into the nerve ending.
...
PMID:Stimulation by surangin B of endogenous amino acid release from synaptosomes. 1450 34

Parasites have developed a wide variety of physiological functions to survive within the specialized environments of the host. Regarding energy metabolism, which represents an essential factor for survival, parasites adapt low oxygen tension in host mammals using metabolic systems that differ substantially from those of the host. Most parasites do not use free oxygen available within the host, but employ systems other than oxidative phosphorylation for ATP synthesis. Furthermore, parasites display marked changes in mitochondrial morphology and components during the life cycle, and these represent very interesting elements of biological processes such as developmental control and environmental adaptation. The enzymes in parasite-specific pathways offer potential targets for chemotherapy. Cyanide-insensitive trypanosome alternative oxidase (TAO) is the terminal oxidase of the respiratory chain of long slender bloodstream forms of the African trypanosome, which causes sleeping sickness. Recently, the most potent inhibitor of TAO to date, ascofuranone, was isolated from the phytopathogenic fungus, Ascochyta visiae. The inhibitory mechanisms of ascofuranone have been revealed using recombinant enzyme. Parasite-specific respiratory systems are also found in helminths. The NADH-fumarate reductase system in mitochondria form a final step in the phosphoenolpyruvate carboxykinase (PEPCK)-succinate pathway, which plays an important role in anaerobic energy metabolism for the Ascaris suum adult. Enzymes in this system, such as NADH-rhodoquinone reductase (complex I) and rhodoquinol-fumarate reductase (complex II), form promising targets for chemotherapy. In fact, a specific inhibitor of nematode complex I, nafuredin, has been found in mass-screening using parasite mitochondria.
...
PMID:Parasite mitochondria as drug target: diversity and dynamic changes during the life cycle. 1452 69

Aspergillus fumigatus is an unusual pathogen in immunocompetent individuals; its incidence has increased in the last decades in patients immunocompromised, like those with chronic granulomatosis disease and AIDS. The aim of this study was to identify differences between the respiratory chain of host and the fungus planning to use the later as a pharmacological target. We evaluated respiration, membrane potential and oxidative phosphorylation of mitochondria of the spheroplasts of A. fumigatus in situ, after permeabilization with digitonin. Firstly, a functional respiratory chain (complex I-V) was demonstrated: adenosine 5'-diphosphate (ADP) induced an oligomycin-sensitive transition from resting to phophorylating respiration in the presence of the oxidizable substrates malate, glutamate, alpha-ketoglutarate, pyruvate, dihydroorotate, succinate, N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) and exogenous NADH. In addition, the ability of the fungus to oxidize exogenous NADH, as well as the insensitivity of its respiration to rotenone, in association with the sensitivity to flavone, indicate the presence of an alternative NADH-ubiquinone oxidoreductase; the partial sensitivity of respiration to antimycin A and cyanide, in association with the sensitivity to benzohydroxamic acid, indicates the presence of an alternative oxidase. The fatty acid-uncoupled respiration was partly reversed by bovine serum albumin (BSA) and guanosine 5'-triphosphate (GTP) and was insensitive to either carboxyatractyloside or ADP. These results, together with evidences obtained using antibodies raised against uncoupling protein (UCP) from potato, indicate in addition, the presence of an uncoupling protein in the respiratory chain of A. fumigatus.
...
PMID:In situ evidence of an alternative oxidase and an uncoupling protein in the respiratory chain of Aspergillus fumigatus. 1459 41

Rapid and complete tissue reoxygenation is a prime goal of present stroke therapy. However, reoxygenation may trigger detrimental cascades that partially antagonize beneficial effects. It was our goal to investigate selective grading of reoxygenation with targeting of single mitochondrial complexes in murine hippocampal slices. Population spike amplitude (PSAP) and NADH were measured during hypoxic hypoxia (15 min) and recovery (45 min). With onset of reoxygenation, slices were treated for different times with amobarbital (1 mM), malonate (2 mM), or cyanide (1 mM), inhibitors of mitochondrial complex I, II, or IV, respectively. Other slices were treated with nicotinamide (1 mM). Posthypoxic recovery of PSAP increased from 32% +/- 43% of onset in control slices to 52% +/- 59% (P <.05) upon treatment with amobarbital for 1 min and to 62% +/- 37% (P <.05) upon treatment with malonate. With nicotinamide, posthypoxic recovery improved to 73% +/- 25% (P <.05). Oxidation of NADH was prolonged upon treatment with amobarbital, whereas no change in NADH oxidation was observed with malonate and nicotinamide. Thus, grading of reoxygenation with selective targeting of mitochondrial complex I or II but not of complex IV improves outcome upon reoxygenation in murine hippocampal slices.
...
PMID:Graded reoxygenation with chemical inhibition of oxidative phosphorylation improves posthypoxic recovery in murine hippocampal slices. 1474 58

The NADH:ubiquinone oxidoreductase (complex I) couples the transfer of electrons from NADH to ubiquinone with the translocation of protons across the membrane. Recently, it was demonstrated that complex I from Klebsiella pneumoniae translocates sodium ions instead of protons. Experimental evidence suggested that complex I from the close relative Escherichia coli works as a primary sodium pump as well. However, data obtained with whole cells showed the presence of an NADH-induced electrochemical proton gradient. In addition, Fourier transform IR spectroscopy demonstrated that the redox reaction of the E. coli complex I is coupled to a protonation of amino acids. To resolve this contradiction we measured the properties of isolated E. coli complex I reconstituted in phospholipids. We found that the NADH:ubiquinone oxidoreductase activity did not depend on the sodium concentration. The redox reaction of the complex in proteoliposomes caused a membrane potential due to an electrochemical proton gradient as measured with fluorescent probes. The signals were sensitive to the protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP), the inhibitors piericidin A, dicyclohexylcarbodi-imide (DCCD), and amiloride derivatives, but were insensitive to the sodium ionophore ETH-157. Furthermore, monensin acting as a Na(+)/H(+) exchanger prevented the generation of a proton gradient. Thus, our data demonstrated that the E. coli complex I is a primary electrogenic proton pump. However, the magnitude of the pH gradient depended on the sodium concentration. The capability of complex I for secondary Na(+)/H(+) antiport is discussed.
...
PMID:The Escherichia coli NADH:ubiquinone oxidoreductase (complex I) is a primary proton pump but may be capable of secondary sodium antiport. 1497 Feb 14

Plants, some fungi, and protists contain a cyanide-resistant, alternative mitochondrial respiratory pathway. This pathway branches at the ubiquinone pool and consists of an alternative oxidase encoded by the nuclear gene Aox1. Alternative pathway respiration is only linked to proton translocation at Complex 1 (NADH dehydrogenase). Alternative oxidase expression is influenced by stress stimuli-cold, oxidative stress, pathogen attack-and by factors constricting electron flow through the cytochrome pathway of respiration. Control is exerted at the levels of gene expression and in response to the availability of carbon and reducing potential. Posttranslational control involves reversible covalent modification of the alternative oxidase and activation by specific carbon metabolites. This dynamic system of coarse and fine control may function to balance upstream respiratory carbon metabolism and downstream electron transport when these coupled processes become imbalanced as a result of changes in the supply of, or demand for, carbon, reducing power, and ATP.
...
PMID:ALTERNATIVE OXIDASE: From Gene to Function. 1501 79

Mitochondria-produced reactive oxygen species (ROS) are thought to contribute to cell death caused by a multitude of pathological conditions. The molecular sites of mitochondrial ROS production are not well established but are generally thought to be located in complex I and complex III of the electron transport chain. We measured H(2)O(2) production, respiration, and NADPH reduction level in rat brain mitochondria oxidizing a variety of respiratory substrates. Under conditions of maximum respiration induced with either ADP or carbonyl cyanide p-trifluoromethoxyphenylhydrazone,alpha-ketoglutarate supported the highest rate of H(2)O(2) production. In the absence of ADP or in the presence of rotenone, H(2)O(2) production rates correlated with the reduction level of mitochondrial NADPH with various substrates, with the exception of alpha-ketoglutarate. Isolated mitochondrial alpha-ketoglutarate dehydrogenase (KGDHC) and pyruvate dehydrogenase (PDHC) complexes produced superoxide and H(2)O(2). NAD(+) inhibited ROS production by the isolated enzymes and by permeabilized mitochondria. We also measured H(2)O(2) production by brain mitochondria isolated from heterozygous knock-out mice deficient in dihydrolipoyl dehydrogenase (Dld). Although this enzyme is a part of both KGDHC and PDHC, there was greater impairment of KGDHC activity in Dld-deficient mitochondria. These mitochondria also produced significantly less H(2)O(2) than mitochondria isolated from their littermate wild-type mice. The data strongly indicate that KGDHC is a primary site of ROS production in normally functioning mitochondria.
...
PMID:Mitochondrial alpha-ketoglutarate dehydrogenase complex generates reactive oxygen species. 1535 89

This study was undertaken to determine whether nitric oxide (NO) can affect platelet responses through the inhibition of energy production. It was found that NO donors: S-nitroso-N-acetylpenicyllamine, SNAP, (5-50 microM) and sodium nitroprusside, SNP, (5-100 microM) inhibited collagen- and ADP-induced aggregation of porcine platelets. The corresponding IC50 values for SNAP and SNP varied from 5 to 30 microM and from 9 to 75 microM, respectively. Collagen- and thrombin-induced platelet secretion was inhibited by SNAP (IC50 = 50 microM) and by SNP (IC50 = 100 microM). SNAP (20-100 microM), SNP (10-200 microM) and collagen (20 microg/ml) stimulated glycolysis in intact platelets. The degree of glycolysis stimulation exerted by NO donors was similar to that produced by respiratory chain inhibitors (cyanide and antimycin A) or uncouplers (2,4-dinitrophenol). Neither the NO donors nor the respiratory chain blockers affected glycolysis in platelet homogenate. SNAP (20-100 microM) and SNP (50-200 microM) inhibited oxygen consumption by platelets. The effect of SNP and SNAP on glycolysis and respiration was not reduced by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one, a selective inhibitor of NO-stimulated guanylate cyclase. SNAP (5-100 microM) and SNP (10-300 microM) inhibited the activity of platelet cytochrome oxidase and had no effect on NADH:ubiquinone oxidoreductase and succinate dehydrogenase. Blocking of the mitochondrial energy production by antimycin A slightly affected collagen-evoked aggregation and strongly inhibited platelet secretion. The results indicate that: 1) in porcine platelets NO is able to diminish mitochondrial energy production through the inhibition of cytochrome oxidase, 2) the inhibitory effect of NO on platelet secretion (but not aggregation) can be attributed to the reduction of mitochondrial energy production.
...
PMID:Nitric oxide and platelet energy metabolism. 1544 39

Ustilago maydis mitochondria contain the four classical components of the electron transport chain (complexes I, II, III, and IV), a glycerol phosphate dehydrogenase, and two alternative elements: an external rotenone-insensitive flavone-sensitive NADH dehydrogenase (NDH-2) and an alternative oxidase (AOX). The external NDH-2 contributes as much as complex I to the NADH-dependent respiratory activity, and is not modulated by Ca2+, a regulatory mechanism described for plant NDH-2, and presumed to be a unique characteristic of the external isozyme. The AOX accounts for the 20% residual respiratory activity after inhibition of complex IV by cyanide. This residual activity depends on growth conditions, since cells grown in the presence of cyanide or antimycin A increase its proportion to about 75% of the uninhibited rate. The effect of AMP, pyruvate and DTT on AOX was studied. The activity of AOX in U. maydis cells was sensitive to AMP but not to pyruvate, which agrees with the regulatory characteristics of a fungal AOX. Interestingly, the presence of DTT during cell permeabilisation protected the enzyme against inactivation. The pathways of quinone reduction and quinol oxidation lack an additive behavior. This is consistent with the competition of the respiratory components of each pathway for the quinol/quinone pool.
...
PMID:The mitochondrial respiratory chain of Ustilago maydis. 1545 Sep 62

Plant mitochondria differ from those of mammals, since they incorporate an alternative electron transport pathway, which branches at ubiquinol to an alternative oxidase (AOX), characteristically inhibited by salicylhydroxamic acid (SHAM). Another feature of plant mitochondria is that besides complex I (EC 1.6.5.3) they possess alternative NAD(P)H-dehydrogenases insensitive to rotenone. Many stress conditions are known to alter the expression of the alternative electron transport pathway in plant mitochondria. In the present study we investigated the effects of some thiol reagents and Ca(2+) on potato mitochondrial respiratory chain presenting different activities of the alternative respiratory components AOX and external NADH dehydrogenase, a condition induced by previous treatment of potato tubers (Solanum tuberosum L., cv. Bintje) to cold stress. The results showed that Ca(2+) presented an inhibitory effect on AOX pathway in potato mitochondria energized with NADH or succinate, which was only now observed when the cytochrome pathway was inhibited by cyanide. When the cytochrome pathway was functional, Ca(2+) stimulated the external NADH dehydrogenase. Diamide was a potent AOX inhibitor and this effect was only now observed when the cytochrome pathway was inactive, as was the case for the calcium ion. Mersalyl inhibited the externally located NADH dehydrogenase and had no effect on AOX activity. The results may represent an important function of Ca(2+) on the alternative mitochondrial enzymes NADH-DH(ext) and AOX.
...
PMID:Sensitivities of the alternative respiratory components of potato tuber mitochondria to thiol reagents and Ca2+. 1576 67


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---