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

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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)

The formation of glutathione radicals, the evolution of nascent oxygen or the peroxidatic reaction with catalase complex I are considered as possible mechanisms for the oxidation of mercury vapor by red blood cells. To select among these, the uptake of atomic mercury by erythrocytes from different species was studied and related to their various activities of catalase (hydrogenperoxide : hydrogen-peroxide oxidoreductase, EC 1.11.1.6) and glutathione peroxidase (glutathione : hydrogen-peroxide oxidoreductase, EC 1.11.1.9). A slow and continuous infusion of diluted H2O2 was used to maintain steady concentrations of complex I. 1% red cell supsensions were found most suitable showing high rates of Hg uptake and yielding still enough cells for subsequent determinations. The results indicate that the oxidation of mercury depends upon the H2O2-generation rate and upon the specific acticity of red-cell catalase. The oxidation occurred in a range of the catalase-H2O2 reaction where the evolution of oxygen could be excluded. Compounds reacting with complex I were shown to be effective inhibitors of the mercury uptake. GSH-peroxidase did not participate in the oxidation but rather, was found to inhibit it by competing with catalase for hydrogen peroxide. These findings support the view that elemental mercury is oxidized in erythrocytes by a peroxidatic reaction with complex I only.
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PMID:Enzymatic oxidation of mercury vapor by erythrocytes. 65 39

While gustation in the hamster has been extensively studied at the behavioral and physiological level, very little is known about the central anatomy of the taste system. The purpose of this study was to trace the connections of the parabrachial nucleus (PBN) in the golden Syrian hamster (Mesocricetus auratus) using wheat germ agglutinin-conjugated horseradish peroxidase. The PBN is the site of the second central synapse for the ascending gustatory system and receives taste afferents from the nucleus of the solitary tract. Following large injections into the PBN, anterogradely transported label was seen in the lateral hypothalamus, dorsal thalamus, bed nucleus of the stria terminalis, and amygdala. The anatomy of the two primary targets, the ventral posteromedial thalamus and central nucleus of the amygdala, is described based on Nissl-stained material, and acetylcholinesterase and NADH dehydrogenase histochemistry. Injections into these two regions revealed different patterns of efferents within the PBN. Following injections into the thalamus, retrogradely labelled cell bodies were distributed throughout the PBN subdivisions bilaterally, but concentrated in the central medial (CM) and external lateral (EL) subdivisions. Following injections into the amygdala, retrogradely labelled cell bodies were primarily in the ipsilateral PBN EL, while anterogradely transported label was distributed throughout much of the ipsilateral PBN. The majority of CM efferents projecting to the thalamus were elongate cells, whereas the majority of CM efferents to the amygdala were round-oval cells. These results indicate that the ascending central gustatory system changes from a serial pathway (nucleus of the solitary tract-PBN) to a parallel organization consisting of two major projections, the parabrachio-thalamo-cortical and parabrachio-amygdaloid pathways.
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PMID:Organization of parabrachial nucleus efferents to the thalamus and amygdala in the golden hamster. 137 87

Quantitative cytochemical, immunocytochemical, autoradiographic and electron cytochemical investigations have been used to compare osteoclasts with multinucleate giant cells that had been freshly obtained from the same animal. The levels of beta-acid galactosidase activity, the DNA in individual nuclei and the cellular protein content were similar in both cell types. However, osteoclasts generally possessed greater acid phosphatase and NADH dehydrogenase activity but lower levels of fluoride-inhibited non-specific esterase activity than multinucleate giant cells. The acid phosphatase activity in multinucleate giant cells was completely inhibited by 100 mM tartrate, but in osteoclasts only a 20% reduction in activity was observed. Formation of multinucleate giant cells in a "bone microenvironment" (thin bone slices) did not increase their content of tartrate-resistant acid phosphatase activity. Moreover, in osteoclasts, endogenous peroxidase activity was undetectable but present in several granules within the cytoplasm of multinucleate giant cells. Osteoclasts and multinucleate giant cells displayed a similar microtubules distribution, but calcitonin, which induced rearrangement of microtubules and cellular contraction in osteoclasts, had no effect on multinucleate giant cells. Thus, these investigations reveal both similarities and differences between these two syncytia and support the hypothesis that osteoclasts and multinucleate giant cells are related. Possibly osteoclasts arise from monocyte progenitors before commitment to a macrophage lineage has occurred.
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PMID:A quantitative cytochemical investigation of osteoclasts and multinucleate giant cells. 174 63

The production of H2O2 by brain mitochondria was monitored employing a new technique based on the horseradish peroxidase dependent oxidation of acetylated ferrocytochrome c. It was shown that brain mitochondria release H2O2 by an intermediate autooxidation at the QH2-cytochrome c oxidoreductase level (induced by antimycin A and inhibited by myxothiazol). With both succinate and pyruvate plus malate this H2O2 release is inhibited at high substrate concentrations. With pyruvate plus malate a second source of H2O2 could be detected, apparently from autoxidation at the NADH dehydrogenase level. With alpha-glycerophosphate some H2O2 derives from autooxidation at the alpha-glycerophosphate dehydrogenase. The NADH dehydrogenase dependent, but not the QH2-cytochrome c oxidoreductase dependent H2O2 was significantly stimulated upon depletion of the mitochondrial glutathione.
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PMID:Pathways of hydrogen peroxide generation in guinea pig cerebral cortex mitochondria. 340 Dec 32

Dopamine, due to metabolism by monoamine oxidase or autoxidation, can generate toxic products such as hydrogen peroxide, oxygen-derived radicals, semiquinones, and quinones and thus exert its neurotoxic effects. Intracerebroventricular injection of dopamine into rats pretreated with the monoamine oxidase nonselective inhibitor pargyline caused mortality in a dose-dependent manner with LD50 = 90 micrograms. Norepinephrine was less effective with LD50 = 141 micrograms. The iron chelator desferrioxamine completely protected against dopamine-induced mortality. In the absence of pargyline more rats survived, indicating that the products of dopamine enzymatic metabolism are not the main contributors to dopamine-induced toxicity. Biochemical analysis of frontal cortex and striatum from rats that received a lethal dose of dopamine did not show any difference from control rats in lipid and protein peroxidation and glutathione reductase and peroxidase activities. Moreover, dopamine significantly reduced the formation of iron-induced malondialdehyde in vitro, thus suggesting that earlier events in cell damage are involved in dopamine toxicity. Indeed, dopamine inhibited mitochondrial NADH dehydrogenase activity with IC50 = 8 microM, and that of norepinephrine was twice as much (IC50 = 15 microM). Dopamine-induced inhibition of NADH dehydrogenase activity was only partially reversed by desferrioxamine, which had no effect on norepinephrine-induced inhibition. These results suggest that catecholamines can cause toxicity not only by inducing an oxidative stress state but also possibly through direct interaction with the mitochondrial electron transport system. The latter was further supported by the ability of ADP to reverse dopamine-induced inhibition of NADH dehydrogenase activity in a dose-dependent manner.
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PMID:Dopamine neurotoxicity: inhibition of mitochondrial respiration. 783 65

The objective of this study was to explore the possible cause(s) underlying the previously observed, age-related increase in the rate of mitochondrial H2O2 release in the housefly. The hypothesis that an imbalance between different respiratory complexes may be a causal factor was tested. Cytochrome c oxidase activity was found to sharply decline in the latter part of the life span of the flies. Effects of different substrates and respiratory inhibitors were determined in order to ascertain if a decrease in cytochrome c oxidase activity could be responsible for the increased H2O2 release. H2O2 was measured spectrofluorometrically using horseradish peroxidase and p-hydroxphenylacetate as an indicator. Neither NADH-linked substrates nor succinate caused a stimulation of H2O2 production. H2O2 release by mitochondria, inhibited with rotenone and antimycin A, was greatly increased upon supplementation with alpha-glycerophosphate; however, the further addition of KCN or myxothiazol, to such preparations, caused a depression of H2O2 generation. In contrast, relatively low concentrations of KCN or myxothiazol were found to stimulate H2O2 release in insect mitochondria supplemented with alpha-glycerophosphate and exposed to rotenone, but not antimycin A. Results are interpreted to suggest that partial inhibition of cytochrome c oxidase activity can lead to the stimulation of mitochondrial H2O2 production in the housefly at site(s) other than NADH dehydrogenase and ubisemiquinone/cytochrome b region; a possible source may be glycerophosphate dehydrogenase.
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PMID:Aging, cytochrome oxidase activity, and hydrogen peroxide release by mitochondria. 839 19

The rate constants of H2O2 decomposition, interaction of catalase complex I with H2O2, and the effective rate constants of catalase inactivation during enzymatic catalysis (k(in)) were determined by transformation of complete kinetic curves of H2O2 decomposition by catalase in reversed micelles of Aerosol OT (AOT) in octane and aqueous solution. Effects of hydration of micelles and AOT, H2O2, and catalase concentrations in the micellar systems on each of three kinetic constants were investigated. Optimal conditions were found which provide for high operational stability and catalytic activity of catalase in micellar systems versus aqueous solutions. Stability of catalase enhances (decreased k(in)) in the presence of reduced glutathione and ethanol in AOT micelles. In reversed AOT micelles, catalase partially dissociates to subunits because their peroxidase activity was demonstrable in cumene hydroperoxide-dependent oxidation of tetramethylbenzidine. Catalase dissociation to monomers is significantly decreased in mixed micelles composed of AOT, Triton X-45, Triton X-100, or Tween-85 and octanol.
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PMID:[Catalytic properties of catalase in microemulsions of surface-active agents in octane]. 899 90

The cDNA encoding the smallest membrane-anchoring subunit (QPs3) of bovine heart mitochondrial succinate-ubiquinone reductase was cloned and sequenced. This cDNA is 1330 base pairs long with an open reading frame of 474 base pairs that encodes the 103 amino acid residues of mature QPs3 and a 55-amino acid residue presequence. The cDNA insert has an 820-base pair long 3'-untranslated region, including a poly(A) tail. The molecular mass of QPs3, deduced from the nucleotide sequence, is 10,989 Da. QPs3 is a very hydrophobic protein; the hydropathy plot of the amino acid sequence reveals three transmembrane helices. Previous photoaffinity labeling studies of succinate-ubiquinone reductase, using 3-azido-2-methyl-5-methoxy[3H]-6-decyl-1,4-benzoquinone ([3H]azido-Q), identified QPs3 as one of the putative Q-binding proteins in this reductase. An azido-Q-linked peptide with a retention time of 66 min is obtained by high performance liquid chromatography of the chymotrypsin digest of carboxymethylated and succinylated [3H]azido-Q-labeled QPs3 purified from labeled succinate-ubiquinone reductase by a procedure involving phenyl-Sepharose 4B column chromatography, preparative SDS-polyacrylamide gel electrophoresis, and acetone precipitation. The amino acid sequence of this peptide is NH2-L-N-P-C-S-A-M-D-Y-COOH, corresponding to residues 29-37. The structure of QPs3 in the inner mitochondrial membrane is proposed based on the hydropathy profile of the amino acid sequence, on the predicted tendencies to form alpha-helices and beta-sheets, and on immunobinding of Fab' fragmenthorseradish peroxidase conjugates prepared from antibodies against two synthetic peptides, corresponding to the NH2 terminus region and the loop connecting helices 2 and 3 of QPs3, in mitoplasts and submitochondrial particles. The ubiquinone-binding domain in the proposed model of QPs3 is probably located at the end of transmembrane helix 1 toward the C-side of the mitochondrial inner membrane.
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PMID:The smallest membrane anchoring subunit (QPs3) of bovine heart mitochondrial succinate-ubiquinone reductase. Cloning, sequencing, topology, and Q-binding domain. 921 43

Diphenyleneiodonium (DPI) has frequently been used to inhibit reactive oxygen species (ROS) production mediated by flavoenzymes, particularly NAD(P)H oxidase. This study was undertaken to examine if DPI could also inhibit production of superoxide and H2O2 by mitochondria, the major source of cellular ROS. Detection of mitochondrial superoxide by lucigenin-derived chemiluminescence (CL) with unstimulated monocytes/macrophages showed that DPI at concentrations that inhibit NAD(P)H oxidase markedly diminished the production of superoxide by mitochondrial respiration. Similarly, the extracellular H2O2 derived from mitochondrial respiration as detected by luminol-derived CL in the presence of horseradish peroxidase was also greatly reduced by DPI. DPI was as potent as rotenone in inhibiting the production of superoxide and H2O2 by mitochondrial respiration. With substrate-supported isolated mitochondria, DPI was shown to reduce mitochondrial superoxide production probably through inhibiting NADH-ubiquinone oxidoreductase (complex I).
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PMID:Diphenyleneiodonium, an NAD(P)H oxidase inhibitor, also potently inhibits mitochondrial reactive oxygen species production. 987 31

Isoniazid is the most widely used antituberculosis drug. Genetic studies in Mycobacterium smegmatis identified the inhA-encoded, NADH-dependent enoyl acyl carrier protein reductase as the primary target for this drug. A reactive form of isoniazid inhibits InhA by reacting with the NAD(H) cofactor bound to the enzyme active site forming a covalent adduct (isonicotinic acyl NADH) that is apt to bind with high affinity. Resistance can occur by increased expression of InhA or by mutations that lower the enzyme's affinity to NADH. Both of these resistance mechanisms are observed in 30% of clinical tuberculosis isolates. Mutation in katG, which encodes catalase peroxidase, is the most common source for resistance. Another mechanism for isoniazid resistance, in M. smegmatis, occurs by defects in NADH dehydrogenase (Ndh) of the respiratory chain. Genetic data indicated that ndh mutations confer resistance by lowering the rate of NADH oxidation and increasing the intracellular NADH/NAD+ ratio. An increased amount of NADH may prevent formation of isonicotinic acyl NADH or may promote displacement of the isonicotinic acyl NADH from InhA. While our studies have identified this mechanism in M. smegmatis, results reported in early literature lead us to believe that it can occur in Mycobacterium tuberculosis.
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PMID:Mechanisms for isoniazid action and resistance. 994 10


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