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)

An ubiquinone-binding protein (QP) was purified from mitochondrial NADH-ubiquinone reductase (Complex I). Complex I was separated into 3 fragments: a fraction of hydrophobic proteins, that of soluble iron-sulfur protein (IP) and soluble NADH dehydrogenase of flavoprotein by a procedure involving the resolution with DOC and cholate, followed by ethanol and ammonium acetate fractionations. About 40% of the total ubiquinone was recovered in the IP fragment which consisted of 12 polypeptides. The QP was purified from the IP fragment with a hydrophobic affinity chromatography. SDS-polyacrylamide gel electrophoresis showed that the purified QP corresponded to 14-kDa polypeptide of the IP fragment and was a different protein from the QP (12.4 kDa) in Complex III. The purified QP (14 kDa) contained one mol ubiquinone per mol. The ubiquinone-depleted IP fragment could rebind ubiquinone. These results indicate that an ubiquinone-binding site in Complex I is on the 14-kDa polypeptide of the IP fragment.
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PMID:An ubiquinone-binding protein in mitochondrial NADH-ubiquinone reductase (Complex I). 309 20

The detergent mono-n-dodecyl octaoxyethylene ether tightly bound to mitochondrial electron-transport particles and below its critical micellar concentration inhibited the NADH oxidase activity, but not the succinate oxidase activity. The result indicates that the inhibition site is in the Complex I segment. The detergent inhibited rotenone-sensitive NADH-ubiquinone reductase activity, but not NADH-ferricyanide reductase activity, of isolated Complex I. Partial removal of phospholipids from Complex I from 18.8% (w/w) to 14.5% significantly decreased its susceptibility to the inhibitor as well as to rotenone. These results show that the binding site of the detergent responsible for the inhibition lies between the NADH dehydrogenase of flavoprotein and ubiquinone in Complex I and that the binding of the detergent to the site requires phospholipids.
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PMID:Selective inhibition of mitochondrial NADH-ubiquinone reductase (Complex I) by an alkyl polyoxyethylene ether. 309 34

An NADH dehydrogenase complex was isolated from the plasma membranes of aerobically grown Paracoccus denitrificans cells by extraction with NaBr and purification on an NAD-agarose column. The NADH-ubiquinone-1 reductase activity of the isolated NADH dehydrogenase complex was about 10 times higher than that of the NaBr extract. The preparation was composed of 10 (6 major and 4 minor) unlike polypeptides, and lacked identifiable components and activities characteristic of other enzyme complexes of the oxidative phosphorylation system. The purified enzyme contained noncovalently bound FMN, nonheme iron, and acid-labile sulfide. The ratio of FMN to nonheme iron to acid-labile sulfide was 1:13 approximately 14:11 approximately 12, suggestive of the presence of multiple iron-sulfur clusters. The isolated NADH dehydrogenase complex cross-reacted with antisera to beef heart mitochondrial complex I and protein fraction derived therefrom, indicating the presence in the Paracoccus enzyme of antigenic sites similar to those in the intact complex I and its iron-sulfur protein and possibly hydrophobic protein fractions.
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PMID:Purification and characterization of NADH dehydrogenase complex from Paracoccus denitrificans. 309 11

Complex I (NADH-ubiquinone reductase) is a complex system located in the inner mitochondrial membrane and has the ability to catalyse several different enzymatic reactions concerned in electron transport. It is known to be one of the first components of the respiratory chain to be damaged by ischemia. Our results, using autolysis in the rat heart as experimental model, indicate that the NADH dehydrogenase system was impaired relatively early during ischemia while transhydrogenation and NADPH dehydrogenation appeared to be relatively resistant.
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PMID:Changes in NADH-ubiquinone reductase (complex I) with autolysis in the rat heart as experimental model. 309 11

Muscle biopsy specimens from two patients with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) were studied biochemically. 14CO2 production rates from (1-14C)pyruvate, (U-14C)malate, and (1-14C)2-ketoglutarate were all decreased in intact mitochondria in both patients. Rotenone-sensitive NADH cytochrome c reductase activities were decreased to 8% (patient 1) and 6% (patient 2) of control values; succinate cytochrome c reductase and cytochrome c oxidase values were within normal limits. These results indicate that both patients have a defect of NADH-CoQ reductase of the respiratory chain and that MELAS can be brought about by a defect of NADH-CoQ reductase.
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PMID:Two cases of NADH-coenzyme Q reductase deficiency: relationship to MELAS syndrome. 310 Jul 53

1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) and its metabolite, 1-methyl-4-phenylpyridine (MPP+), have been shown to cause a number of lesions in dopaminergic pathways of the nigro-striatal region of the brain. However, data on the effects of these neurotoxins on other aspects of brain metabolism are scarce. The data presented here show that MPTP and MPP+ inhibit glucose oxidation via the tricarboxylic acid cycle, and acetylcholine synthesis in synaptosomal preparations from rat forebrain. Monoamine oxidase B inhibitors (e.g., pargyline, MDL 72145) relieve the inhibition caused by MPTP but not MPP+. The inhibitory effects of MPP+ on glucose oxidation and acetylcholine synthesis are a consequence of the decreased glucose metabolism in synaptosomes and are consistent with its role as an inhibitor of the Complex I (NADH-CoQ reductase) of the mitochondrial respiratory chain.
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PMID:Effects of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine and its metabolite 1-methyl-4-phenylpyridine on acetylcholine synthesis in synaptosomes from rat forebrain. 310 94

The NADH-ubiquinone reductase activity of the respiratory chains of several organisms was inhibited by the carboxyl-modifying reagent N,N'-dicyclohexylcarbodiimide (DCCD). This inhibition correlated with the presence of an energy-transducing site in this segment of the respiratory chain. Where the NADH-quinone reductase segment involved an energy-coupling site (e.g., in bovine heart and rat liver mitochondria, and in Paracoccus denitrificans, Escherichia coli, and Thermus thermophilus HB-8 membranes), DCCD acted as an inhibitor of ubiquinone reduction by NADH. By contrast, where energy-coupling site 1 was absent (e.g., in Saccharomyces cerevisiae mitochondria and Bacillus subtilis membranes), there was no inhibition of NADH-ubiquinone reductase activity by DCCD. In the bovine and P. denitrificans systems, DCCD inhibition was pseudo first order with respect to incubation time, and reaction order with respect to inhibitor concentration was close to unity, indicating that inhibition resulted from the binding of one inhibitor molecule per active unit of NADH-ubiquinone reductase. In the bovine NADH-ubiquinone reductase complex (complex I), [14C]DCCD was preferentially incorporated into two subunits of molecular weight 49,000 and 29,000. The time course of labeling of the 29,000 molecular weight subunit with [14C]DCCD paralleled the time course of inhibition of NADH-ubiquinone reductase activity.
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PMID:Inhibition of NADH-ubiquinone reductase activity by N,N'-dicyclohexylcarbodiimide and correlation of this inhibition with the occurrence of energy-coupling site 1 in various organisms. 311 26

Chronic administration of the NADH-CoQ reductase inhibitor, diphenyleneiodonium to rats at two dose levels, 1.0 and 1.5 mg/kg per day, caused a 40% and 60% reduction, respectively, in the in vitro rate of NAD-linked respiration by skeletal muscle mitochondria. At the highest dose, muscle fatigue, lactic acidosis and an over-utilization of phosphocreatine was observed in the gastrocnemius muscle during mild stimulation of 1 Hz frequency. The resynthesis of phosphocreatine following muscle stimulation was about 2 fold slower in the treated animal group. At the low dose, no significant biochemical changes were observed during muscle stimulation at 4 Hz. The results are discussed in terms of skeletal muscle "oxidative reserve", twitch tension maintenance and the relevance to the human diseased state of mitochondrial myopathy.
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PMID:An animal model of mitochondrial myopathy: a biochemical and physiological investigation of rats treated in vivo with the NADH-CoQ reductase inhibitor, diphenyleneiodonium. 312 47

Responses to exercise were obtained in six patients with a biochemically diagnosed enzyme deficiency at the level of NADH-CoQ reductase. The responses were compared with those of a control group, consisting of fourteen patients with inexplicable dyspnoea or muscle pain during exercise, for which no firm diagnosis could be established and of which the exercise responses were in the normal range. Metabolic, ventilatory and cardiological variables such as oxygen uptake (VO2), minute ventilation (VE), respiratory exchange ratio (R), heart rate (HR) and difference in blood lactate or base-excess (BE) between rest and maximal workload were measured during cycle ergometry from samples obtained in the last minutes of four minute periods, in which the load increased stepwise by 30 W per four minutes. The threshold of lactate metabolism (Tlact) was assumed to be equal to the threshold determined both by the VO2 at which the VE versus VO2 response started to deviate from a straight line and the ventilatory equivalent for oxygen (VE/VO2) showed a minimum (Tvent), Tvent was estimated from the mean of these values, obtained by linear and parabolic regression analysis respectively. In the patient group, mean values for symptom limited maximal VO2 (VO2,max,sl; % of VO2,max,ref), Tvent (% of VO2,max,ref) and R at maximal workload were 43, 17 and 1.23 against 85, 47 and 1.06 for the same variables in the control group, respectively. The differences were highly significant (p less than 0.001; p less than 0.005 for mean R difference). Mean maximal HR and mean change in blood lactate or BE were not significantly different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Exercise responses in patients with an enzyme deficiency in the mitochondrial respiratory chain. 313 46

The mitochondrial NADH:ubiquinone oxidoreductase complex (Complex I) is inhibited by N,N'-dicyclohexylcarbodiimide (DCCD), and this inhibition correlates with incorporation of radioactivity from [14C]DCCD into a Complex I subunit of Mr 29,000 (Yagi, T. (1987) Biochemistry 26, 2822-2828). Resolution of [14C]DCCD-labeled Complex I in the presence of NaClO4 showed that the labeled Mr 29,000 subunit was in the hydrophobic fraction of the enzyme. This fraction, which contains greater than 17 unlike polypeptides, was subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the Mr 29,000 subunit, containing bound [14C]DCCD, was isolated and purified. The amino acid composition and partial sequence of this subunit corresponded to those predicted from the mitochondrial DNA for the product of the mtDNA gene designated ND-1. The identity of the Mr 29,000 subunit with the ND-1 gene product was further confirmed by immunoblotting and immunoprecipitation experiments, using the hydrophobic fraction of [14C]DCCD-labeled Complex I and antiserum to a C-terminal undecapeptide synthesized on the basis of the human mitochondrial ND-1 nucleotide sequence. Thus, it appears that the DCCD-binding subunits of the respiratory chain Complexes I, III, and IV and in certain organisms the DCCD-binding subunit of the ATP synthase complex (Complex V) are all mtDNA products.
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PMID:Identification of the dicyclohexylcarbodiimide-binding subunit of NADH-ubiquinone oxidoreductase (Complex I). 314


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