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)

In a unique Chinese hamster mutant, Gal-32, the mitochondrially encoded subunits of cytochrome c oxidase (CO I, II, III) and NADH dehydrogenase (ND 1-6) are greatly decreased while other mitochondrially synthesized proteins, such as ATPase subunits 6 and 8, are less affected. Pulse-chase experiments with [35S]methionine demonstrated that the reduced amounts of CO I and ND 5 subunits in Gal-32 are not the result of more rapid protein degradation. No differences in sizes of mtRNAs were detected between wild type and mutant using Northern blotting. The steady state levels of both heavy and light strand mtDNA transcripts were elevated in Gal-32: CO I mRNA was 1.5-fold higher in the mutant than in the wild type; ND 5 mRNA was 1.9-fold higher; ND 6 precursor RNAs were 1.4-fold higher and ATPase 6 and 8 mRNA (a single transcript) was 2.7-fold higher. Thus, the amounts of translation products are roughly correlated with the levels of mRNAs. The reduced levels of mitochondrially synthesized proteins in Gal-32 are the result of decreased translation of specific mRNAs, not increased degradation of mtRNAs.
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PMID:Elevated mitochondrial RNA in a Chinese hamster mutant deficient in the mitochondrially encoded subunits of NADH dehydrogenase and cytochrome c oxidase. 169 38

Steady-state levels of 12 S and 16 S mitochondrial (mt) rRNAs and four mRNAs (NADH dehydrogenase subunits 3 and 4/4L, cytochrome c oxidase subunit III, H(+)-ATPase subunits 6/6L) were estimated by hybridization of cellular RNA with cloned human mt DNA fragments during hypoxia of HeLa cells. When the partial pressure of oxygen (pO2) was shifted from 135 to 15 Torr, the level of all mRNAs coordinately decreased more than 95% in 48 h, while that of rRNAs remained virtually unchanged. mRNA levels recovered within 4-6 h of reexposure to normoxia. The depression was observed at pO2 less than 40 Torr, the physiological pO2 in peripheral tissues. During these transitions, the growth rate of HeLa cells and the copy number of mt DNA per cell remained unchanged. The degradation rate of mt mRNAs in the presence of cordycepin was not affected by pO2. In contrast to the in vivo results, the potential activity of transcription in isolated mitochondria assayed under optimum conditions was not affected by previous hypoxic exposure of the cells. These observations provide evidence for the existence of a new mechanism controlling mitochondrial gene transcription.
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PMID:Hypoxic depression of mitochondrial mRNA levels in HeLa cell. 170 27

Saline extracts of burn eschar (CEBE) and normal skin (CENS) caused inhibition to mitochondrial respiration and inner membrane function. Ethyl acetate extracts from CEBE (D1) and CENS (D'1) caused depression of the Respiratory Control Ratio, (RCR), an inhibition of respiration rate in state 3 and stimulation to state 4 respiration. Excellent linear correlations exist between the degree of inhibition to state 3, rate of stimulation to state 4 respiration and the logarithm of doses of D1 and D'1. The effective dose ranges (0.75-0.25 mg/ml for D1 and 4-1 mg/ml for D'1) differ by one order of magnitude. The activity of NADH dehydrogenase and succinate dehydrogenase of mitochondria after incubation with the highest toxic dose of D1 or D'1 remained normal. Dinitrophenol (DNP)-stimulated respiration was moderately inhibited by D1 and D'1. No change of oligomycin-sensitive ATPase activity was demonstrated. Exogenous malondialdehyde (MDA) did not show any inhibitory effect. Preliminary studies show that D1 contains a family of free fatty acids (FFA). Incubation of normal mitochondria with D1 increased the content of saturated FFA and a decrease of unsaturated FFA. The role of other peroxidative products is under investigation.
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PMID:Inhibition of mitochondrial respiratory function by an organic solvent extractable component from an extract of burn eschar. 183 77

The effects of arachidonic acid on the enzyme complexes in the electron transport system were investigated using submitochondrial particles from rat brain. Arachidonic acid irreversibly inhibited NADH-CoQ oxidoreductase (complex I) activity, but had no effect on the activities of succinate-CoQ oxidoreductase (complex II), CoQH2-cytochrome c oxidoreductase (complex III), cytochrome c oxidase (complex IV), ATPase (complex V), glutamate dehydrogenase, and malate dehydrogenase up to 50 microM. The inhibition was dose-dependent with an IC50 value of 110 nmol/mg protein. The Lineweaver-Burk plot revealed that the inhibition by arachidonic acid was noncompetitive against CoQ with a Ki value of 33 microM and uncompetitive against NADH with a Ki value of 22 microM.
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PMID:Selective inhibition of NADH-CoQ oxidoreductase (complex I) of rat brain mitochondria by arachidonic acid. 190 30

The amino acid sequences of 15 sugar permeases of the bacterial phosphoenolpyruvate-dependent phosphotransferase system (PTS) were divided into four homologous segments, and these segments were analyzed to give phylogenetic trees. The permease segments fell into four clusters: the lactose-cellobiose cluster, the fructose-mannitol cluster, the glucose-N-acetylglucosamine cluster, and the sucrose-beta-glucoside cluster. Sequences of the glucitol and mannose permeases (clusters 5 and 6, respectively) were too dissimilar to establish homology with the other permeases, but short regions of statistically significant sequence similarities were noted. The functional and structural relationships of these permease segments are discussed. Some of the homologous PTS permeases were found to exhibit sufficient sequence similarity to subunits 4 and 5 of the eukaryotic mitochondrial NADH dehydrogenase complex to suggest homology. Moreover, subunits 4 and 5 of this complex appeared to be homologous to each other, suggesting that these PTS and mitochondrial proteins comprise a superfamily. The integral membrane subunits of the evolutionarily divergent mannose PTS permease, the P and M subunits, exhibited limited sequence similarity to subunit 6 of the mitochondrial F1F0-ATPase and subunit 5b of cytochrome oxidase, respectively. These results suggest that PTS sugar permeases and mitochondrial proton-translocating proteins may be related, although the possibility of convergent evolution cannot be ruled out.
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PMID:Evolutionary relationships among the permease proteins of the bacterial phosphoenolpyruvate: sugar phosphotransferase system. Construction of phylogenetic trees and possible relatedness to proteins of eukaryotic mitochondria. 192 Apr 54

Zinc deficiency (ZD) is teratogenic in rats, and fetal skeletal defects are prominent. To elucidate further the effects of maternal ZD in the fetal skeleton, we performed a morphological and histochemical study of tibial growth plate (GP) in ZD rat fetuses. The histochemical study included the identification of calcium, of hydrolytic enzymes associated with the process of calcification, and of oxidative enzymes related to energy production and to the synthesis of proteoglycans. Pregnant Sprague-Dawley rats were fed (1) a control diet (76.4 micrograms Zn/g diet) ad libitum (group C), (2) a zinc-deficient diet (0 micrograms/g) ad libitum (group ZD), or (3) the control diet pair-fed to the ZD rats (group PF). On day 21 of gestation, laparotomies were performed, the fetuses were removed, and fetal tibiae obtained. Specimens were stained with hematoxylin-eosin (H&E) and Masson Trichrome and were processed for identification of alkaline phosphatase, adenosine triphosphatase, succinic dehydrogenase, NADH dehydrogenase, and calcium. The morphologic patterns found in ZD fetal tibiae indicated defects in various cell types implicated in bone metabolism. Staining for hydrolytic enzymes revealed alterations in the size and distribution of matrix vesicles and a weaker staining for ATPase in ZD fetuses. Staining for oxidative enzymes was overall more intense in ZD fetal tibiae. ZD fetuses also presented irregular and defective calcification. These findings indicate that severe maternal ZD in the rat results in structural and functional alterations in the GP of fetal bone, leading to a defective endochondral ossification.
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PMID:Changes in the fetal tibial growth plate secondary to maternal zinc deficiency in the rat: a histological and histochemical study. 196 89

The plasma membrane fraction of chicken osteoclasts was purified utilizing 20% continuous Percoll gradients. Biochemical marker enzyme analysis (ouabain-sensitive Na+,K(+)-ATPase and 5'-nucleotidase) indicated that plasma membrane enrichment was 11.87-fold and 7.25-fold, respectively, and contamination with mitochondria, endoplasmic reticulum, and lysosomes was low as determined by succinic dehydrogenase, NADH dehydrogenase, and N-acetylglucosaminidase activities, respectively. SDS latency of Na+,K(+)-ATPase and 5'-nucleotidase activities of the isolated plasma membranes revealed that 43-50% of vesicles were sealed, with 10-16% in the inside-out orientation, depending on the membrane fraction used. Electron microscopy confirmed the vesicular nature of the plasma membrane fraction. The plasma membrane Ca2(+)-ATPase had a high-affinity (KCa = 0.22 microM; Vmax = 0.16 mumol/mg per min) and a low-affinity (KCa = 148 microM; Vmax = 0.37 mumol/mg per min) component. Calmodulin (0.12 microM) had no effect on Ca2(+)-ATPase activity. However, trifluoperazine (0.1 mM), a calmodulin antagonist, strongly inhibited especially the high-affinity component of the enzyme. Vanadate and lanthanum also caused inhibition. In the presence of CDTA, a potent Ca2+ and Mg2+ chelating agent, high-affinity Ca2(+)-ATPase activity was abolished, indicating that trace Mg2+ was essential for activity. The Ca2(+)-ATPase substrate curve using ATP showed a high-affinity (Km = 12.3 microM; Vmax = 0.022 mumol/mg per min) and a low-affinity (Km = 43.8 microM; Vmax = 0.278 mumol/mg per min) component. These results demonstrate that osteoclasts have a plasma membrane Ca2(+)-ATPase with characteristics similar to the enzyme responsible for active calcium extrusion in other cells.
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PMID:Characterization of a Ca2(+)-ATPase in osteoclast plasma membrane. 214 47

Bovine heart submitochondrial particles (SMP) were exposed to continuous fluxes of hydroxyl radical (.OH) alone, superoxide anion radical (O2-) alone, or mixtures of .OH and O2-, by gamma radiolysis in the presence of 100% N2O (.OH exposure), 100% O2 + formate (O2- exposure), or 100% O2 alone (.OH + O2- exposure). Hydrogen peroxide effects were studied by addition of pure H2O2. NADH dehydrogenase, NADH oxidase, succinate dehydrogenase, succinate oxidase, and ATPase activities (Vmax) were rapidly inactivated by .OH (10% inactivation at 15-40 nmol of .OH/mg of SMP protein, 50-90% inactivation at 600 nmol of .OH/mg of SMP protein) and by .OH + O2- (10% inactivation at 20-80 nmol of .OH + O2-/mg of SMP protein, 45-75% inactivation at 600 nmol of .OH + O2-/mg of SMP protein). Importantly, O2- was a highly efficient inactivator of NADH dehydrogenase, NADH oxidase, and ATPase (10% inactivation at 20-50 nmol of O2-/mg of SMP protein, 40% inactivation at 600 nmol of O2-/mg of SMP protein), a mildly efficient inactivator of succinate dehydrogenase (10% inactivation at 150 nmol of O2-/mg of SMP protein, 30% inactivation at 600 nmol of O2-/mg of SMP protein), and a poor inactivator of succinate oxidase (less than 10% inactivation at 600 nmol of O2-/mg of SMP protein). H2O2 partially inactivated NADH dehydrogenase, NADH oxidase, and cytochrome oxidase, but even 10% loss of these activities required at least 500-600 nmol of H2O2/mg of SMP protein. Cytochrome oxidase activity (oxygen consumption supported by ascorbate + N,N,N',N'-tetramethyl-p-phenylenediamine) was remarkably resistant to oxidative inactivation, with less than 20% loss of activity evident even at .OH, O2-, OH + O2-, or H2O2 concentrations of 600 nmol/mg of SMP protein. Cytochrome c oxidase activity, however (oxidation of, added, ferrocytochrome c), exhibited more than a 40% inactivation at 600 nmol of .OH/mg of SMP protein. The .OH-dependent inactivations reported above were largely inhibitable by the .OH scavenger mannitol. In contrast, the O2(-)-dependent inactivations were inhibited by active superoxide dismutase, but not by denatured superoxide dismutase or catalase. Membrane lipid peroxidation was evident with .OH exposure but could be prevented by various lipid-soluble antioxidants which did not protect enzymatic activities at all.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The oxidative inactivation of mitochondrial electron transport chain components and ATPase. 216 88

The main target of local anaesthetics on nervous tissue is the sodium channel. Molecular biology and electrophysiology have shown different mechanisms of action on this sodium channel, which depend on the chemical structure and electrostatic charge of the local anaesthetic molecule. There are two main types of action, shown up on the isolated axon, a direct one on the sodium channel itself and an alteration in the lipids surrounding the channel. These effects have been shown on the isolated axon and explain the anaesthetic effect by an inhibition of the sodium current. Experimental studies have also shown the effects of local anaesthetics on different organelles within the cell, and so on intracellular metabolism. Mitochondrial energetic metabolism, and therefore ATP synthesis, is reduced by local anaesthetics at several levels. The respiratory enzyme chain is inhibited by small concentrations of local anaesthetic, especially NADH dehydrogenase and ubiquinone succinate dehydrogenase. Moreover, local anaesthetics increase the mitochondrial membrane permeability to protons, thus removing the moving force behind ATPase activity in ATP synthesis; this leads to a drastic fall in available energy. This effect is further increased by a direct inhibition of ATPase and ATP/ADP translocation. Other enzyme systems of other organelles are also disturbed by local anaesthetics, such as the endoplasmic reticular Ca++ ATPase, which is inhibited, so altering the calcium concentration within the cytosol. Local anaesthetics also inhibit lipolysis and glycogenesis. Receptors such as the acetylcholine receptors are blocked by local anaesthetics. The mechanism of action of these drugs on all these protein systems is two-fold: an alteration of protein structure, but also of the lipids surrounding them.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Molecular mechanism of action of local anesthetics]. 245 46

Physical fixation by rapid freezing followed by freeze-fracture and deep-etching has provided the means for potentially seeing the three-dimensional arrangement in the native state of particles on mitochondrial inner membranes. We have used these techniques to study the tubular cristae of Paramecium in the hope of determining the arrangement of F1 complexes, their abundance, and location in the membranes. We also sought information regarding other respiratory complexes in these membranes. Our results, supported by stereo pairs, show that F1 complexes are arranged as a double row of particles spaced at 12 nm along each row as a zipper following the full length of the outer curve of the helically shaped tubular cristae. There are an average of 1,500 highly ordered F1 complexes per micrometer squared of 50-nm tubular cristae surface. The F1 complexes definitely lie outside the membranes in their native state. Other particle subsets, also nonrandomly arrayed, were seen. One such population located along the inner helical curve consisted of large 13-nm-wide particles that were spaced at 30 nm center-to-center. Such particles, because of their large size and relative abundance when compared to F1 units, resemble complex I of the respiratory complexes. Any models attempting to understand the coupling of respiratory complexes with F0F1 ATPase in Paramecium must take into account a relatively high degree of order and potential immobility of at least some of these integral membrane complexes.
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PMID:An investigation of mitochondrial inner membranes by rapid-freeze deep-etch techniques. 252 61


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