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)

Postmortem changes in mitochondrial respiratory enzymes (Complex I-IV and NAD(+)-linked dehydrogenases in the TCA cycle) were studied in mouse brains and human frontal lobes. In mouse brains, activities of the enzymes studied were generally stable for as long as 12 h after cervical dislocation, except for the alpha-ketoglutarate dehydrogenase complex and NADP(+)-linked isocitrate dehydrogenase. In human frontal cortices, only NADH-ubiquinone reductase (Complex I) activity showed significant negative correlation with the duration between the patient's death and the freezing of the brain. No correlations between the activities of the enzymes studied and the age of the patients were noted. As most of our patients were 50 years of age or above, absence of the correlation cannot be extended to younger patients. From our observation, it was felt that analyses of these mitochondrial enzymes in human autopsy brains would give meaningful data. Preliminary observation in Parkinson's disease revealed a small but a significant decrease in the activity of Complex III in the striatum as compared with the control. Although, significance of our observation is not yet known, further studies on this line appear to be important to elucidate pathogenesis of Parkinson's disease.
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PMID:Postmortem changes in mitochondrial respiratory enzymes in brain and a preliminary observation in Parkinson's disease. 235 87

It was shown that the membrane-bound complex I is fully inactive in the absence of NADH during the reverse electron transfer from succinate to NAD+. The enzyme activation is attained by preincubation of submitochondrial particles with low concentrations of NADH; the activating effect persists after a complete oxidation of the latter during long-term (several hours) aerobic incubation. The experimental results suggest that complex I contains a redox component, whose reduction by NADH and aerobic oxidation are not involved in the overall catalytic reaction. An experimental scheme is proposed, according to which the key role of such a component is ascribed to the tightly bound ubiquinone; the activation and inactivation of the enzyme are due to a slow reversible redox conversion (ubiquinone in equilibrium ubisemiquinone), whereas the catalytic act involves a rapid reversible conversion (ubisemiquinone in equilibrium ubiquinol). It was demonstrated that the "redox" mechanism of the inactivation-activation reaction determines the strong dependence of activity of the reverse electron transfer on the mode of preparation of submitochondrial particles. The coupling properties of the submitochondrial particulate membrane and the activities of enzymes involved in the reverse electron transfer are stable at room temperature for over 14 hours.
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PMID:[Hysteresis behavior of complex I in delta mu H+-dependent reduction of NAD+ succinate]. 249 1

An artificial proton gradient provided sufficient energy to drive reverse electron transport from succinate to NADH:ubiquinone oxidoreductase in chromatophores isolated from Rhodospirillum rubrum. The pH gradient created was able to reduce NAD+. In chromatophores, the optimal rate of NAD+ reduction was about 0.4-0.45 mumol NADH formed/min.mumol bacteriochlorophyll at delta pH 3. The presence of oligomycin was an obligate factor in the assay in order to observe the maximal rate of NAD+ reduction. The rate of NADH formation was dependent on the size of the induced pH gradient. The total NADH formed had a threshold value for the imposed delta pH. The effect of different inhibitors and uncouplers was demonstrated. Comparison between ATP, PPi, and light with the pH jump driven NAD+ reduction rate was studied.
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PMID:delta pH driven energy-linked NAD+ reduction in Rhodospirillum rubrum chromatophores. 250 79

The yeast C. parapsilosis CBS7157 is strictly dependent on oxidative metabolism for growth since it lacks a fermentative pathway. It is nevertheless able to grow on high glucose concentrations and also on a glycerol medium supplemented with antimycin A or drugs acting at the level of mitochondrial protein synthesis. Besides its normal respiratory chain C. parapsilosis develops a second electron transfer chain antimycin A-insensitive which allows the oxidation of cytoplasmic NAD(P)H resulting from glycolytic and hexose monophosphate pathways functioning through a route different from the NADH-coenzyme Q oxidoreductase described in S. cerevisiae or from the alternative pathways described in numerous plants and microorganisms. The second respiratory chain of C. parapsilosis involves 2 dehydrogenases specific for NADH and NADPH respectively, which are amytal and mersalyl sensitive and located on the outer face of the inner membrane. Since this antimycin A-insensitive pathway is fully inhibited by myxothiazol, it was hypothesized that electrons are transferred to a quinone pool that is different from the classical coenzyme Q-cytochrome b cycle. Two inhibitory sites were evidenced with myxothiazol, one related to the classical pathway, the other to the second pathway and thus, the second quinone pool could bind to a Q-binding protein at a specific site. Elimination of this second pool leads to a fully antimycin A-sensitive NADH oxidation, whereas its reincorporation in mitochondria allows recovery of an antimycin A-insensitive, myxothiazol sensitive NADH oxidation. The third step in this second respiratory chain involves a specific pool of cytochrome c which can deliver electrons either to a third phosphorylation site or to an alternative oxidase, cytochrome 590. This cytochrome is inhibited by high cyanide concentrations and salicylhydroxamates.
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PMID:The second respiratory chain of Candida parapsilosis: a comprehensive study. 250 62

The steady-state kinetics of oxidation of the mitochondrial NADH: ubiquinone oxidoreductase (complex I, EC 1.6.99.3) by artificial electron acceptors--p-quinones and inorganic complexes has been investigated. A limiting stage in the NADH: ferricyanide reductase reaction is a reductive half-reaction. Ferricyanide interacts with negative-charged protein groups taking part in the NADH binding. The rate constants of the quinone reduction by complex I vary from 1.10(6) to 4.10(3) M-1s-1. The NADH, NAD+ and ADP-ribose inhibition data indicate that oxidizers in the rotenono-insensitive reaction interact with the redox centre near the NAD+/NADH binding site, most probably with FMN.
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PMID:[Reaction of complex I of the mitochondrial electron transport chain with artificial oxidizers]. 251 53

Nineteen structural analogs of 1-methyl-4-phenylpyridinium (MPP+) were studied for their capacity to inhibit the mitochondrial oxidation of NAD+-linked substrates and the aerobic oxidation of NADH in inner membrane preparations from cardiac mitochondria. In the majority of cases, a good correlation was found between the two inhibition effects monitored. A few compounds were effective inhibitors of NADH oxidase but had only marginal effects on mitochondrial respiration. From studies of their accumulation by mitochondria, it appears likely that the latter compounds are not effectively concentrated by intact mitochondria by the electrical gradient and, in part for this reason, cannot reach sufficiently high concentrations at the appropriate binding site of NADH dehydrogenase. In addition, evidence is presented that the penetration of pyridinium analogs to the inhibition site in the NADH dehydrogenase complex may also be rate limiting. The data support the thesis that, for a substituted tetrahydropyridine to be acutely neurotoxic, its pyridinium oxidation product must be actively accumulated in the mitochondria and must inhibit NADH-ubiquinone oxidoreductase in its membrane environment.
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PMID:Structural dependence of the inhibition of mitochondrial respiration and of NADH oxidase by 1-methyl-4-phenylpyridinium (MPP+) analogs and their energized accumulation by mitochondria. 259 58

Initial Polytron treatment with subsequent exposure to the bacterial proteinase Nagarse has been shown to result in the isolation of two distinct populations of cardiac mitochondria, subsarcolemmal and interfibrillar mitochondria, respectively. Although these populations have been shown to possess distinct biochemical properties, few studies have been reported which document the potential differences in their response to pathological insult. We therefore examined the effect of acute hypoxia with or without reoxygenation as well as treatment with phosphate on oxidative phosphorylation on both groups of mitochondria. Freshly-isolated interfibrillar mitochondria (IFM) exhibited significantly higher respiratory values, with the exception of the ADP:O ratios, than subsarcolemmal mitochondria (SLM). With pyruvate-malate as respiratory substrate, 40 minutes hypoxia alone produced no effect on SLM whereas a stimulation in respiration was seen in IFM. A 40-minute reoxygenation period depressed the oxidative phosphorylation rate in SLM whereas it was stimulated in IFM. These treatments did not produce any effect in either population when succinate was the substrate of choice. Because of the latter observation, the possibility that increased lability of complex I of the electron transport chain accounted for the differences associated with NAD-linked substrates was studied by assessing NADH oxidation of sonicated mitochondria following the treatments. SLM exhibited enhanced permeability to exogenous NADH as well as increased sensitivity to sonication following either hypoxia or hypoxia/reoxygenation compared to IFM. Compared to hypoxia/reoxygenation, increasing concentrations of phosphate (5-15 mM) produced a marked depression in oxidative phosphorylation of SLM whereas IFM were relatively resistant. The toxic effects of phosphate were much more evident with pyruvate-malate as substrates; with succinate, oxidative phosphorylation of IFM was not depressed by phosphate whereas only a slight depression was observed with SLM. The latter population similarly exhibited reduced NADH oxidation following phosphate treatment whereas IFM were unaffected. Our studies show a differential sensitivity of two mitochondrial populations to hypoxia/reoxygenation, and, more markedly to phosphate. Since these effects were much less pronounced with succinate-linked respiration and since they were associated with defective NADH oxidation in SLM, it is suggested that the differences between the two populations may be accounted for by the increased lability of complex I of SLM due to hypoxia/reoxygenation or phosphate.
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PMID:Acute effects of hypoxia and phosphate on two populations of heart mitochondria. 260 32

Deficiency of complex I is one of the most commonly reported defects of the mitochondrial respiratory chain in man. Clinical evidence of tissue specific expression of complex I deficiency has not previously been confirmed biochemically. We report here slow oxidation of NAD+-linked substrates, low activity of complex I and low amounts of immunoreactive complex I peptides in skeletal muscle mitochondria from a patient with muscle weakness and lactic acidosis. In liver mitochondria complex I activity was normal and all the immunoreactive subunits of complex I were present in normal amounts.
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PMID:Tissue specific defect of complex I of the mitochondrial respiratory chain. 271 85

The alkalophile NADH dehydrogenase (NADH: 2,6-dichlorophenolindophenol oxidoreductase) [EC 1.6.99.3] consists of two identical subunits of 65 kDa, and each subunit contains the catalytic and liposome-binding regions. On treatment with trypsin, the polypeptide exhibiting the liposome-binding property in one of the subunits was digested to form an enzymatically active hetero-dimer (40 and 65 kDa), and then the polypeptide in the other subunit was digested to form an active homo-dimer (40 and 40 kDa). The hetero-dimer bound to liposomes, but the homo-dimer did not. Kinetic analysis showed that removal of one or two of the polypeptides in the enzyme slightly affects its kinetic parameters. For all the enzyme species, NAD inhibited competitively with respect to NADH and non-competitively with respect to 2,6-dichlorophenolindophenol. The partially determined amino acid sequence of this alkalophile enzyme suggested that (i) a long random-coiled peptide (58 amino acid residues) or a portion of the peptide is located between the polypeptides with liposome-binding and catalytic properties, (ii) the polypeptide exhibiting liposome-binding property is in the amino terminal region of the enzyme, (iii) the amino acid sequences around the subtilisin and trypsin cleavage sites of the peptide are hydrophilic and on the surface of the protein molecule and therefore are susceptible to digestion, and (iv) the FAD-binding site is located near the amino terminal region of the catalytic region.
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PMID:Tryptic digestion of NADH dehydrogenase from alkalophilic Bacillus. 276 20

By means of fluorimetric measurement and by direct determination of intracellular NAD+ and NADH contents, it was proved that the respiration rate of Paracoccus denitrificans cells utilizing glucose is limited by processes preceding NADH oxidation in the respiratory chain, so that the membrane NADH dehydrogenase is not saturated by its substrate. In the separated membrane fraction on saturation with exogenous NADH the main limiting factor is represented by NADH: ubiquinone oxidoreductase.
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PMID:Control of respiration rate in non-growing cells of Paracoccus denitrificans. 282 53


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