Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00387 (NADH)
 21,936 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have seen that there is no simple answer to the question 'what controls respiration?' The answer varies with (a) the size of the system examined (mitochondria, cell or organ), (b) the conditions (rate of ATP use, level of hormonal stimulation), and (c) the particular organ examined. Of the various theories of control of respiration outlined in the introduction the ideas of Chance & Williams (1955, 1956) give the basic mechanism of how respiration is regulated. Increased ATP usage can cause increased respiration and ATP synthesis by mass action in all the main tissues. Superimposed on this basic mechanism is calcium control of matrix dehydrogenases (at least in heart and liver), and possibly also of the respiratory chain (at least in liver) and ATP synthase (at least in heart). In many tissues calcium also stimulates ATP usage directly; thus calcium may stimulate energy metabolism at (at least) four possible sites, the importance of each regulation varying with tissue. Regulation of multiple sites may occur (from a teleological point of view) because: (a) energy metabolism is branched and thus proportionate regulation of branches is required in order to maintain constant fluxes to branches (e.g. to proton leak or different ATP uses); and/or (b) control over fluxes is shared by a number of reactions, so that large increases in flux requires stimulation at multiple sites because each site has relatively little control. Control may be distributed throughout energy metabolism, possibly due to the necessity of minimizing cell protein levels (see Brown, 1991). The idea that energy metabolism is regulated by energy charge (as proposed by Atkinson, 1968, 1977) is misleading in mammals. Neither mitochondrial ATP synthesis nor cellular ATP usage is a unique function of energy charge as AMP is not a significant regulator (see for example Erecinska et al., 1977). The near-equilibrium hypothesis of Klingenberg (1961) and Erecinska & Wilson (1982) is partially correct in that oxidative phosphorylation is often close to equilibrium (apart from cytochrome oxidase) and as a consequence respiration and ATP synthesis are mainly regulated by (a) the phosphorylation potential, and (b) the NADH/NAD+ ratio. However, oxidative phosphorylation is not always close to equilibrium, at least in isolated mitochondria, and relative proximity to equilibrium does not prevent the respiratory chain, the proton leak, the ATP synthase and ANC having significant control over the fluxes. Thus in some conditions respiration rate correlates better with [ADP] than with phosphorylation potential, and may be relatively insensitive to mitochondrial NADH/NAD+ ratio.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Control of respiration and ATP synthesis in mammalian mitochondria and cells. 159 89

Defective complex I activity has been linked to Parkinson's disease and Huntington's disease, but little is known of the regional distribution of this enzyme in the brain. We have developed a quantitative autoradiographic assay using [3H]dihydrorotenone ([3H]DHR) to label and localize complex I in brain tissue sections. Binding was specific and saturable and in the cerebellar molecular layer had a KD of 11.5 +/- 1.3 nM and a Bmax of 11.0 +/- 0.4 nCi/mg of tissue. Unlabeled rotenone and 1-methyl-4-phenylpyridinium ion competed effectively for DHR binding sites. Binding was markedly enhanced by 100 microM NADH. The distribution of complex I in brain, as revealed by DHR autoradiography, is unique but somewhat similar to that of cytochrome oxidase (complex IV). This assay may provide new insight into the roles of complex I in brain function and neurodegeneration.
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PMID:Quantitative autoradiography of dihydrorotenone binding to complex I of the electron transport chain. 162 44

Studies on brain mitochondria are complicated by the regional, cellular, and subcellular heterogeneity of the central nervous system. This study was performed using synaptic and nonsynaptic mitochondria obtained from cortex, hippocampus, and striatum of male Sprague-Dawley rats (3 months old). Ubiquinone content, detected by HPLC analysis, was about 1.5 nmol/mg protein with an approximate CoQ9/CoQ10 molecular ratio of 2:1. The activities of several respiratory chain complexes were also studied (succinate-cyt. c reductase, NADH-cyt. c reductase, succinate-DCIP, ubiquinol2-cyt. c reductase, and cytochrome oxidase), and generally found to be higher in mitochondria from cortex than from other regions. Study of the activities of some of these enzymes vs. 1/T (Arrhenius plots) showed a straight line with an activation energy between 7 and 10 kcal/mol in all the three areas considered. Only CoQ2H2-cyt. c reductase activity revealed a biphasic temperature dependence. Also anisotropy (as fluorescence polarization) of the hydrophobic probe DPH showed a deviation from linearity; the break points for both enzymatic activity and anisotropy were found at about 23-24 degrees C.
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PMID:Structural and functional aspects of the respiratory chain of synaptic and nonsynaptic mitochondria derived from selected brain regions. 164 1

The activities of enzymes related to energy metabolism in the gastrocnemius and soleus muscles in young-adult (4 months), mature (12 months), and senescent (24 months) rats were compared after continuous (72 consecutive h) exposure to normobaric hypoxia or normoxia after the vasodilator naftidrofuryl or saline solution had been given intraperitoneally for 30 consecutive days. The maximum rats (Vmax) of the following enzyme activities in the crude extract and/or the crude mitochondrial fraction of each muscle specimen were evaluated for: the anaerobic glycolytic pathway (hexokinase, phosphofructokinase, pyruvate kinase, and lactate dehydrogenase), the tricarboxylic acid cycle (citrate synthase, and malate dehydrogenase), the electron transfer chain (cytochrome oxidase), and the NAD+/NADH redox state (total NADH cytochrome c reductase). The significance of differences between the enzyme activities at different ages or under different experimental conditions in the two tissue preparations of the two muscles were determined by ANOVA. MCA and ETA2 were used to evaluate the net effects of the experimental conditions. First, aging did not seem to affect the soleus and gastrocnemius muscles in the same way. In the gastrocnemius muscle, the major changes were seen in enzymes of the glycolytic pathway, in the crude extracts. In the soleus muscle, the more striking changes in enzyme activities as a function of aging were found in the crude mitochondrial fraction. We also found that hypoxia caused more important changes in 12-month-old rats than in those of other ages (especially the enzyme activities of the gastrocnemius muscle). Naftidrofuryl modified the effects of hypoxia only sometimes and further investigations are necessary before we can draw any conclusions about the pharmacological activity of naftidrofuryl in hypoxia.
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PMID:Effects of hypoxia and pharmacological treatment on enzyme activities in skeletal muscle of rats of different ages. 164 27

Oxidation of exogenous NADH by isolated rat liver mitochondria is generally accepted to be mediated by endogenous cytochrome c which shuttles electrons from the outer to the inner mitochondrial membrane. More recently it has been suggested that, in the presence of added cytochrome c, NADH oxidation is carried out exclusively by the cytochrome oxidase of broken or damaged mitochondria. Here we show that electrons can be transferred in and out of intact mitochondria. It is proposed that at the contact sites between the inner and the outer membrane, a "bi-trans-membrane" electron transport chain is present. The pathway, consisting of Complex III, NADH-b5 reductase, exogenous cytochrome c and cytochrome oxidase, can channel electrons from the external face of the outer membrane to the matrix face of the inner membrane and viceversa. The activity of the pathway is strictly dependent on both the activity of the respiratory chain and mitochondrion integrity.
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PMID:Oxidation and reduction of exogenous cytochrome c by the activity of the respiratory chain. 165 29

A 5-month-old boy died of progressive heart failure that started at the age of 3 months. Autopsy revealed a mitochondrial cardiomyopathy and a mitochondrial myopathy of the limb muscle and diaphragm. Cytochemically random defects of cytochrome c oxidase were visualized by light and electron microscopy in the diaphragm and especially the heart muscle, the limb muscle showing a diffuse attenuation whereas the liver and kidneys reacted normally. The activities of NADH-dehydrogenase (complex I) and cytochrome c oxidase (complex IV) were severely diminished (20% residual activity of controls) in the skeletal and heart muscle. In the heart, succinate cytochrome c reductase (complex II/III) was additionally decreased to the same degree. Loss of cytochrome c oxidase activity was based on a reduction of both mitochondrial and nuclear derived subunits in the heart and diaphragm as revealed by immunohistochemical analysis, whereas the limb muscle showed a normal immunoreactive protein content. The results illustrate heterogeneous tissue expression of respiratory chain enzyme defects and demonstrate that a cardiomyopathy may be the leading presentation of a mitochondrial disorder in early infancy.
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PMID:Fatal infantile mitochondrial cardiomyopathy and myopathy with heterogeneous tissue expression of combined respiratory chain deficiencies. 165 34

The biochemical characteristics of the electron transfer chain are evaluated in purified non-synaptic ("free") mitochondria from the forebrain of 60-week-old rats weekly subjected to peroxidative stress (once, twice, or three times) by the electrophilic prooxidant 2-cyclohexene-1-one. The following parameters are evaluated: (a) content of respiratory components, namely ubiquinone, cytochrome b, cytochrome c1, cytochrome c; (b) specific activity of enzymes, namely citrate synthase, succinate dehydrogenase, rotenone-sensitive NADH: cytochrome c reductase, cytochrome oxidase; (c) concentration of reduced glutathione (GSH). Before the first peroxidative stress induction, the rats are administered for 8 weeks by intraperitoneal injection of vehicle, papaverine, delta-yohimbine, almitrine or hopanthenate. The rats are treated also during the week(s) before the second or third peroxidative stress. The cerebral peroxidative stress induces: (a) initially, a decrease in brain GSH concentration concomitant with a decrease in the mitochondrial activity of cytochrome oxidase of aa3-type (complex IV), without changes in ubiquinone and cytochrome b populations; (b) subsequently, an alteration in the transfer molecule cytochrome c and, finally, in rotenone-sensitive NADH-cytochrome c reductase (complex I) and succinate dehydrogenase (complex II). The selective sensitivity of the chain components to peroxidative stress is supported by the effects of the concomitant subchronic treatment with agents acting at different biochemical steps. In fact, almitrine sets limits to its effects at cytochrome c content and aa3-type cytochrome oxidase activity, while delta-yohimbine sets limits to its effects at the level of tricarboxylic acid cycle (citrate synthase) and/or of intermediary between tricarboxylic acid cycle and complex II (succinate dehydrogenase).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sequential damage in mitochondrial complexes by peroxidative stress. 166 94

The maximum rates (Vmax) of some mitochondrial enzyme activities related to energy transduction (citrate synthase, malate dehydrogenase, NADH cytochrome c reductase, cytochrome oxidase) and amino acid metabolism (glutamate dehydrogenase) were evaluated in non-synaptic (free) and synaptic mitochondria from rat hippocampus and striatum. Three types of mitochondria were isolated from control rats aged 4, 8, 12, 16, 20 and 24 months and treated ones with L-acetylcarnitine (100 mg.kg-1, i.p., 60 min). Enzyme activities of non-synaptic and synaptic mitochondria are different in hippocampus and striatum, confirming that a different metabolic machinery exists in various types of brain mitochondria. During aging, enzyme activities behave quite similarly in both areas. In vivo administration of L-acetylcarnitine decreased the enzyme activities related to Krebs' cycle mainly of synaptic mitochondria, suggesting a specific subcellular trigger site of action. The drug increased cytochrome oxidase activity of synaptic and non-synaptic mitochondria, indicating the specificity of molecular interaction with this enzyme.
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PMID:Action of L-acetylcarnitine on different cerebral mitochondrial populations from hippocampus and striatum during aging. 166 44

The maximal rate (Vmax) of some mitochondrial enzyme activities related to energy transduction (citrate synthase, alpha-ketoglutarate dehydrogenase, malate dehydrogenase, succinate dehydrogenase, NADH-cytochrome c reductase, cytochrome oxidase) and amino acid metabolism (glutamate dehydrogenase, glutamate-pyruvate transaminase and glutamate-oxaloacetate transaminase) are evaluated in non synaptic ("free") and intrasynaptic mitochondria from brain hippocampus. The different mitochondrial populations were isolated from rat subjected to single i.p. treatment with saline solution, almitrine (30 mg/kg) and delta-yohimbine (10 mg/kg). In control rats, the mitochondrial populations exhibit different enzymatic patterns. Acute treatment with almitrine decreases cytochrome oxidase activity in intra-synaptic mitochondria, while acute treatment with delta-yohimbine decreases succinate dehydrogenase activity in both types of free and intra-synaptic mitochondria. NADH-cytochrome c reductase activity is also decreased by acute treatment with almitrine ("free" and "synaptic" mitochondria) and delta-yohimbine (synaptic mitochondria only).
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PMID:Factors involved in drug interference on enzyme activities of three mitochondrial populations from rat hippocampus. 180 34

Two cationic, lipophilic laser dyes, 1,1',3,3,3',3'-hexamethylindodicarbocyanine iodide (HIDC) and 1,1',3,3,3',3'-hexamethylindotricarbocyanine iodide (HITC), inhibit bovine heart mitochondrial and Paracoccus denitrificans NADH oxidase activities. The mitochondrial I50 values were 0.5 microM (HIDC) and 1.2 microM (HITC), and the P. denitrificans I50 values 1.2 microM (HIDC) and 1.5 microM (HITC). Neither succinate nor cytochrome oxidase (EC 1.9.3.1) activities were inhibited significantly by either compound, localizing the site of inhibition to the segment of each electron transport chain between NADH and ubiquinone. With submitochrondrial particles (SMP), NADH-dependent reduction of menadione, duroquinone and coenzyme Q1 was inhibited markedly (HIDC was the more potent inhibitor). Using purified complex I, only NADH-dependent reduction of duroquinone and coenzyme Q1 was inhibited markedly (HIDC was the more potent inhibitor) and reduction of menadione was inhibited slightly. With P. denitrificans membrane vesicles, NADH-dependent reduction of menadione, juglone, and coenzyme Q1 was inhibited slightly and duroquinone reduction was inhibited markedly. Membrane-dependent interactions appear to be involved, since the compounds were more inhibitory with membrane preparations than with complex I. The mechanism of inhibition (except for the HIDC effect on coenzyme Q1 reduction with P. denitrificans) appeared to be through the interaction of dye with the rotenone site on NADH-ubiquinone reductase (EC 1.6.99.3), since rotenone-insensitive preparations of complex I and P. denitrificans membrane vesicles were also insensitive to HIDC and HITC inhibition.
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PMID:Inhibitory effects of two structurally related carbocyanine laser dyes on the activity of bovine heart mitochondrial and Paracoccus denitrificans NADH-ubiquinone reductase. Evidence for a rotenone-type mechanism. 190 Jan 56


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