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Sample records for coenzyme ii

  1. Impact of Chemical Analogs of 4-Hydroxybenzoic Acid on Coenzyme Q Biosynthesis: From Inhibition to Bypass of Coenzyme Q Deficiency

    Directory of Open Access Journals (Sweden)

    Fabien Pierrel

    2017-06-01

    Full Text Available Coenzyme Q is a lipid that participates to important physiological functions. Coenzyme Q is synthesized in multiple steps from the precursor 4-hydroxybenzoic acid. Mutations in enzymes that participate to coenzyme Q biosynthesis result in primary coenzyme Q deficiency, a type of mitochondrial disease. Coenzyme Q10 supplementation of patients is the classical treatment but it shows limited efficacy in some cases. The molecular understanding of the coenzyme Q biosynthetic pathway allowed the design of experiments to bypass deficient biosynthetic steps with analogs of 4-hydroxybenzoic acid. These molecules provide the defective chemical group and can reactivate endogenous coenzyme Q biosynthesis as demonstrated recently in yeast, mammalian cell cultures, and mouse models of primary coenzyme Q deficiency. This mini review presents how the chemical properties of various analogs of 4-hydroxybenzoic acid dictate the effect of the molecules on CoQ biosynthesis and how the reactivation of endogenous coenzyme Q biosynthesis may achieve better results than exogenous CoQ10 supplementation.

  2. Coenzyme Q10 effects in neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Meredith Spindler

    2009-11-01

    Full Text Available Meredith Spindler1, M Flint Beal1,2, Claire Henchcliffe1,21Department of Neurology, 2Department of Neuroscience, Weill Medical College of Cornell University, New York, NY, USAAbstract: Coenzyme Q10 (CoQ10 is an essential cofactor in the mitochondrial respiratory chain, and as a dietary supplement it has recently gained attention for its potential role in the treatment of neurodegenerative disease. Evidence for mitochondrial dysfunction in neurodegenerative disorders derives from animal models, studies of mitochondria from patients, identification of genetic defects in patients with neurodegenerative disease, and measurements of markers of oxidative stress. Studies of in vitro models of neuronal toxicity and animal models of neurodegenerative disorders have demonstrated potential neuroprotective effects of CoQ10. With this data in mind, several clinical trials of CoQ10 have been performed in Parkinson’s disease and atypical Parkinson’s syndromes, Huntington’s disease, Alzheimer disease, Friedreich’s ataxia, and amyotrophic lateral sclerosis, with equivocal findings. CoQ10 is widely available in multiple formulations and is very well tolerated with minimal adverse effects, making it an attractive potential therapy. Phase III trials of high-dose CoQ10 in large sample sizes are needed to further ascertain the effects of CoQ10 in neurodegenerative diseases.Keywords: coenzyme Q10, neurodegenerative disease, Parkinson’s disease, Huntington’s disease, mitochondrial dysfunction

  3. Coenzyme Q10 treatment ameliorates acute cisplatin nephrotoxicity in mice

    International Nuclear Information System (INIS)

    Fouad, Amr A.; Al-Sultan, Ali Ibrahim; Refaie, Shereen M.; Yacoubi, Mohamed T.

    2010-01-01

    The nephroprotective effect of coenzyme Q10 was investigated in mice with acute renal injury induced by a single i.p. injection of cisplatin (5 mg/kg). Coenzyme Q10 treatment (10 mg/kg/day, i.p.) was applied for 6 consecutive days, starting 1 day before cisplatin administration. Coenzyme Q10 significantly reduced blood urea nitrogen and serum creatinine levels which were increased by cisplatin. Coenzyme Q10 significantly compensated deficits in the antioxidant defense mechanisms (reduced glutathione level and superoxide dismutase activity), suppressed lipid peroxidation, decreased the elevations of tumor necrosis factor-α, nitric oxide and platinum ion concentration, and attenuated the reductions of selenium and zinc ions in renal tissue resulted from cisplatin administration. Also, histopathological renal tissue damage mediated by cisplatin was ameliorated by coenzyme Q10 treatment. Immunohistochemical analysis revealed that coenzyme Q10 significantly decreased the cisplatin-induced overexpression of inducible nitric oxide synthase, nuclear factor-κB, caspase-3 and p53 in renal tissue. It was concluded that coenzyme Q10 represents a potential therapeutic option to protect against acute cisplatin nephrotoxicity commonly encountered in clinical practice.

  4. Coenzyme metabolism in rat liver transketolase

    International Nuclear Information System (INIS)

    Gorbach, Z.V.; Kubyshin, V.L.; Maglysh, S.S.; Zabrodskaya, S.V.

    1987-01-01

    On the basis of the results of kinetic investigations, two binding sites for hydroxythiamine diphosphate were determined in apotransketolase, with sharply differing values of K/sub i/: (7-22) x 10 -9 and (13.0-19.7) x 10 -8 M. A study was made of the turnover rate of thiamine diphosphate in holotransketolase in rat liver tissue by a radioisotope method, using [ 14 C] thiamine as the labeled precursor. The half-substitution time and rate constant of degradation of the coenzyme in transketolase are close in absolute values to the analogous indices for the protein portion of the enzyme and constitute 153 h and 0.108 day -1 , respectively. Rat liver transketolase exists in vivo in the form of a substituted α-carbanion. Replacement of thiamine diphosphate by hydroxythiamine diphosphate in the holoenzyme has no effect on the formation of the intermediate α-carbanion form of the enzyme

  5. Hepatoprotective effect of taurine and coenzyme Q10 and their ...

    African Journals Online (AJOL)

    stress in rats. Afaf Abbass Sayed ... Keywords: Taurine, Coenzyme Q10, Acrylamide, Oxidative stress, Biochemical profile, ... uses, AA formation in foods has its major routes through .... release of serum inflammatory markers and neutrophil ...

  6. Coenzyme Q10 and Neurological Diseases

    Directory of Open Access Journals (Sweden)

    Gabriele Siciliano

    2009-12-01

    Full Text Available Coenzyme Q10 (CoQ10, or ubiquinone is a small electron carrier of the mitochondrial respiratory chain with antioxidant properties. CoQ10 supplementation has been widely used for mitochondrial disorders. The rationale for using CoQ10 is very powerful when this compound is primary decreased because of defective synthesis. Primary CoQ10 deficiency is a treatable condition, so heightened “clinical awareness” about this diagnosis is essential. CoQ10 and its analogue, idebenone, have also been widely used in the treatment of other neurodegenerative disorders. These compounds could potentially play a therapeutic role in Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, Friedreich’s ataxia, and other conditions which have been linked to mitochondrial dysfunction. This article reviews the physiological roles of CoQ10, as well as the rationale and the role in clinical practice of CoQ10 supplementation in different neurological diseases, from primary CoQ10 deficiency to neurodegenerative disorders.

  7. Biochemical Assessment of Coenzyme Q10 Deficiency

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    Juan Carlos Rodríguez-Aguilera

    2017-03-01

    Full Text Available Coenzyme Q10 (CoQ10 deficiency syndrome includes clinically heterogeneous mitochondrial diseases that show a variety of severe and debilitating symptoms. A multiprotein complex encoded by nuclear genes carries out CoQ10 biosynthesis. Mutations in any of these genes are responsible for the primary CoQ10 deficiency, but there are also different conditions that induce secondary CoQ10 deficiency including mitochondrial DNA (mtDNA depletion and mutations in genes involved in the fatty acid β-oxidation pathway. The diagnosis of CoQ10 deficiencies is determined by the decrease of its content in skeletal muscle and/or dermal skin fibroblasts. Dietary CoQ10 supplementation is the only available treatment for these deficiencies that require a rapid and distinct diagnosis. Here we review methods for determining CoQ10 content by HPLC separation and identification using alternative approaches including electrochemical detection and mass spectrometry. Also, we review procedures to determine the CoQ10 biosynthesis rate using labeled precursors.

  8. Radioprotection of DNA molecule by oxido-reduction's coenzymes

    International Nuclear Information System (INIS)

    Araos, M.S.; Fernandez, M.; Tomicic, I.; Toha, J.C.

    1978-01-01

    The radio protective action of respiratory coenzymes on DNA-water solutions is studied after irradiation with a 60 Co source. Coenzymes were used separately or in mixtures of their oxidized and reduced forms. The dose relative factor (DRF) values evaluated by uv absorbancy measurements of DNA damage were high: 18.03 for the (NAD-FAD-quinone) mixture (a respiratory chain model); 14.91 for (quinone-hydroquinone) mixtures; 14.46 for quinone; 14.27 for hydroquinone; 12.49 for FAD; 7.21 for the (NAD-NADH) mixture; 6.48 for NADH and 3.79 for NAD. No parallelism was found between the DNA coenzymes strong interactions and their protective action, performed by overcoming the indirect radiation damage. Besides, uv irradiation studies give no support to protection through direct energy transfer processes from excited DNA to coenzymes. The high efficiency of the mixtures of oxidized-reduced respiratory coenzymes is discussed in terms of simultaneous and equivalent trapping of recombinable radicals. The high tolerance of these protectors in living cells is emphasized. (author)

  9. Calcium binding and transport by coenzyme Q.

    Science.gov (United States)

    Bogeski, Ivan; Gulaboski, Rubin; Kappl, Reinhard; Mirceski, Valentin; Stefova, Marina; Petreska, Jasmina; Hoth, Markus

    2011-06-22

    Coenzyme Q10 (CoQ10) is one of the essential components of the mitochondrial electron-transport chain (ETC) with the primary function to transfer electrons along and protons across the inner mitochondrial membrane (IMM). The concomitant proton gradient across the IMM is essential for the process of oxidative phosphorylation and consequently ATP production. Cytochrome P450 (CYP450) monoxygenase enzymes are known to induce structural changes in a variety of compounds and are expressed in the IMM. However, it is unknown if CYP450 interacts with CoQ10 and how such an interaction would affect mitochondrial function. Using voltammetry, UV-vis spectrometry, electron paramagnetic resonance (EPR), nuclear magnetic resonance (NMR), fluorescence microscopy and high performance liquid chromatography-mass spectrometry (HPLC-MS), we show that both CoQ10 and its analogue CoQ1, when exposed to CYP450 or alkaline media, undergo structural changes through a complex reaction pathway and form quinone structures with distinct properties. Hereby, one or both methoxy groups at positions 2 and 3 on the quinone ring are replaced by hydroxyl groups in a time-dependent manner. In comparison with the native forms, the electrochemically reduced forms of the new hydroxylated CoQs have higher antioxidative potential and are also now able to bind and transport Ca(2+) across artificial biomimetic membranes. Our results open new perspectives on the physiological importance of CoQ10 and its analogues, not only as electron and proton transporters, but also as potential regulators of mitochondrial Ca(2+) and redox homeostasis.

  10. Coenzyme Q supplementation in pulmonary arterial hypertension

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    Jacqueline Sharp

    2014-01-01

    Full Text Available Mitochondrial dysfunction is a fundamental abnormality in the vascular endothelium and smooth muscle of patients with pulmonary arterial hypertension (PAH. Because coenzyme Q (CoQ is essential for mitochondrial function and efficient oxygen utilization as the electron carrier in the inner mitochondrial membrane, we hypothesized that CoQ would improve mitochondrial function and benefit PAH patients. To test this, oxidized and reduced levels of CoQ, cardiac function by echocardiogram, mitochondrial functions of heme synthesis and cellular metabolism were evaluated in PAH patients (N=8 in comparison to healthy controls (N=7, at baseline and after 12 weeks oral CoQ supplementation. CoQ levels were similar among PAH and control individuals, and increased in all subjects with CoQ supplementation. PAH patients had higher CoQ levels than controls with supplementation, and a tendency to a higher reduced-to-oxidized CoQ ratio. Cardiac parameters improved with CoQ supplementation, although 6-minute walk distances and BNP levels did not significantly change. Consistent with improved mitochondrial synthetic function, hemoglobin increased and red cell distribution width (RDW decreased in PAH patients with CoQ, while hemoglobin declined slightly and RDW did not change in healthy controls. In contrast, metabolic and redox parameters, including lactate, pyruvate and reduced or oxidized gluthathione, did not change in PAH patients with CoQ. In summary, CoQ improved hemoglobin and red cell maturation in PAH, but longer studies and/or higher doses with a randomized placebo-controlled controlled design are necessary to evaluate the clinical benefit of this simple nutritional supplement.

  11. Effect of Simvastatin, Coenzyme Q10, Resveratrol, Acetylcysteine and Acetylcarnitine on Mitochondrial Respiration.

    Science.gov (United States)

    Fišar, Z; Hroudová, J; Singh, N; Kopřivová, A; Macečková, D

    2016-01-01

    Some therapeutic and/or adverse effects of drugs may be related to their effects on mitochondrial function. The effects of simvastatin, resveratrol, coenzyme Q10, acetylcysteine, and acetylcarnitine on Complex I-, Complex II-, or Complex IV-linked respiratory rate were determined in isolated brain mitochondria. The protective effects of these biologically active compounds on the calcium-induced decrease of the respiratory rate were also studied. We observed a significant inhibitory effect of simvastatin on mitochondrial respiration (IC50 = 24.0 μM for Complex I-linked respiration, IC50 = 31.3 μM for Complex II-linked respiration, and IC50 = 42.9 μM for Complex IV-linked respiration); the inhibitory effect of resveratrol was found at very high concentrations (IC50 = 162 μM for Complex I-linked respiration, IC50 = 564 μM for Complex II-linked respiration, and IC50 = 1454 μM for Complex IV-linked respiration). Concentrations required for effective simvastatin- or resveratrol-induced inhibition of mitochondrial respiration were found much higher than concentrations achieved under standard dosing of these drugs. Acetylcysteine and acetylcarnitine did not affect the oxygen consumption rate of mitochondria. Coenzyme Q10 induced an increase of Complex I-linked respiration. The increase of free calcium ions induced partial inhibition of the Complex I+II-linked mitochondrial respiration, and all tested drugs counteracted this inhibition. None of the tested drugs showed mitochondrial toxicity (characterized by respiratory rate inhibition) at drug concentrations achieved at therapeutic drug intake. Resveratrol, simvastatin, and acetylcarnitine had the greatest neuroprotective potential (characterized by protective effects against calcium-induced reduction of the respiratory rate).

  12. Potential administration of lipoic acid and coenzyme Q against ...

    African Journals Online (AJOL)

    Potential administration of lipoic acid and coenzyme Q against adipogensis: target for weight reduction. ... prevents its accumulation in visceral tissues. Further studies should be carried out to examine the mechanistic signals of these nutrients that helps in weight = management. Keywords: lipolysis, obesity, lipoic acid, Co-Q ...

  13. Regulation of autophagy by cytosolic acetyl-coenzyme A

    DEFF Research Database (Denmark)

    Mariño, Guillermo; Pietrocola, Federico; Eisenberg, Tobias

    2014-01-01

    Acetyl-coenzyme A (AcCoA) is a major integrator of the nutritional status at the crossroads of fat, sugar, and protein catabolism. Here we show that nutrient starvation causes rapid depletion of AcCoA. AcCoA depletion entailed the commensurate reduction in the overall acetylation of cytoplasmic p...

  14. Genetics Home Reference: primary coenzyme Q10 deficiency

    Science.gov (United States)

    ... mutations have occurred in the COQ2 , COQ4 , COQ6 , COQ8A , and COQ8B genes. Smaller numbers of mutations in other COQ genes have also been found ... primary coenzyme Q10 deficiency ... Related Information What is a gene? What is a gene mutation and how do mutations occur? How can gene ...

  15. Therapeutic implication of coenzyme Q10 during statin therapy: pros and cons

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    Mir-Jamal Hosseini

    2015-09-01

    Full Text Available Coenzyme Q10 (CoQ10 is a vitamin-like substance, and a natural intermediate of electron transport chain (ETC of mitochondria which can accepts and donates electrons from complex I and complex II. CoQ10 shares a biosynthetic pathway with cholesterol and dolichol thus it can be a potential target of the widely available lipid-lowering drugs. The lipid lowering drugs such as statins, are widely administered to individuals who have high cholesterol levels. This article reviews the a clinical benefits of CoQ10 b association between administration of statin and CoQ10 deficiency and c involvement of CoQ10 in statin-associated myopathy.

  16. Coenzyme Q10: A New Treatment for Hemorrhagic Shock

    Science.gov (United States)

    2014-10-29

    SUBJECT TERMS hemorrhagic shock, ubiquinol, Coenzyme Q10, patient outcome 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18...o leo& to tboOigllll failure. The < Iota fur AlM •1 ha"’ boon ._...runym.,..,; •• ted in p=en~atlons and publiobed tn Expu""’""" P/u<llology. Tho

  17. Thermophilic archaea activate butane via alkyl-coenzyme M formation.

    Science.gov (United States)

    Laso-Pérez, Rafael; Wegener, Gunter; Knittel, Katrin; Widdel, Friedrich; Harding, Katie J; Krukenberg, Viola; Meier, Dimitri V; Richter, Michael; Tegetmeyer, Halina E; Riedel, Dietmar; Richnow, Hans-Hermann; Adrian, Lorenz; Reemtsma, Thorsten; Lechtenfeld, Oliver J; Musat, Florin

    2016-11-17

    The anaerobic formation and oxidation of methane involve unique enzymatic mechanisms and cofactors, all of which are believed to be specific for C 1 -compounds. Here we show that an anaerobic thermophilic enrichment culture composed of dense consortia of archaea and bacteria apparently uses partly similar pathways to oxidize the C 4 hydrocarbon butane. The archaea, proposed genus 'Candidatus Syntrophoarchaeum', show the characteristic autofluorescence of methanogens, and contain highly expressed genes encoding enzymes similar to methyl-coenzyme M reductase. We detect butyl-coenzyme M, indicating archaeal butane activation analogous to the first step in anaerobic methane oxidation. In addition, Ca. Syntrophoarchaeum expresses the genes encoding β-oxidation enzymes, carbon monoxide dehydrogenase and reversible C 1 methanogenesis enzymes. This allows for the complete oxidation of butane. Reducing equivalents are seemingly channelled to HotSeep-1, a thermophilic sulfate-reducing partner bacterium known from the anaerobic oxidation of methane. Genes encoding 16S rRNA and methyl-coenzyme M reductase similar to those identifying Ca. Syntrophoarchaeum were repeatedly retrieved from marine subsurface sediments, suggesting that the presented activation mechanism is naturally widespread in the anaerobic oxidation of short-chain hydrocarbons.

  18. Autotrophic acetyl coenzyme A biosynthesis in Methanococcus maripaludis

    International Nuclear Information System (INIS)

    Shieh, J.; Whitman, W.B.

    1988-01-01

    To detect autotrophic CO 2 assimilation in cell extracts of Methanococcus maripaludis, lactate dehydrogenase and NADH were added to convert pyruvate formed from autotropically synthesized acetyl coenzyme A to lactate. The lactate produced was determined spectrophotometrically. When CO 2 fixation was pulled in the direction of lactate synthesis, CO 2 reduction to methane was inhibited. Bromoethanesulfonate (BES), a potent inhibitor of methanogenesis, enhanced lactate synthesis, and methyl coenzyme M inhibited it in the absence of BES. Lactate synthesis was dependent on CO 2 and H 2 , but H 2 + CO 2 -independent synthesis was also observed. In cell extracts, the rate of lactate synthesis was about 1.2 nmol min -1 mg of protein -1 . When BES was added, the rate of lactate synthesis increased to 2.1 nmol min -1 mg of protein -1 . Because acetyl coenzyme A did not stimulate lactate synthesis, pyruvate synthase may have been the limiting activity in these assays. Radiolabel from 14 CO 2 was incorporated into lactate. The percentages of radiolabel in the C-1, C-2, and C-3 positions of lactate were 73, 33, and 11%, respectively. Both carbon monoxide and formaldehyde stimulated lactate synthesis. 14 CH 2 O was specifically incorporated into the C-3 of lactate, and 14 CO was incorporated into the C-1 and C-2 positions. Low concentrations of cyanide also inhibited autotrophic growth, CO dehydrogenase activity, and autotrophic lactate synthesis. These observations are in agreement with the acetogenic pathway of autotrophic CO 2 assimilation

  19. Breeding of Coenzyme Q10 Produced Strain by Low-Energy Ion Implantation and Optimization of Coenzyme Q10 Fermentation

    International Nuclear Information System (INIS)

    Xu Dejun; Zheng Zhiming; Wang Peng; Wang Li; Yuan Hang; Yu Zengliang

    2008-01-01

    In order to increase the production efficiency of coenzyme Q 10 , the original strain Agrobacterium tumefaciens ATCC 4452 was mutated by means of Nitrogen ions implantation. A mutant strain, ATX 12, with high contents of coenzyme Q 10 was selected. Subsequently, the conditions such as carbohydrate concentration, nitrogen source concentration, inoculum's size, seed age, aeration and temperature which might affect the production of CoQ 10 were investigated in detail. Under optimal conditions, the maximum concentration of the intracellular CoQ 10 reached 200.3 mg/L after 80 h fed-batch fermentation, about 245% increasing in CoQ 10 production after ion implantation, compared to the original strain. (ion beam bioengineering)

  20. Potential role of coenzyme Q10 in facilitating recovery from statin-induced rhabdomyolysis.

    Science.gov (United States)

    Wang, L W; Jabbour, A; Hayward, C S; Furlong, T J; Girgis, L; Macdonald, P S; Keogh, A M

    2015-04-01

    Rhabdomyolysis is a rare, but serious complication of statin therapy, and represents the most severe end of the spectrum of statin-induced myotoxicity. We report a case where coenzyme Q10 facilitated recovery from statin-induced rhabdomyolysis and acute renal failure, which had initially persisted despite statin cessation and haemodialysis. This observation is biologically plausible due to the recognised importance of coenzyme Q10 in mitochondrial bioenergetics within myocytes, and the fact that statins inhibit farnesyl pyrophosphate production, a biochemical step crucial for coenzyme Q10 synthesis. Coenzyme Q10 is generally well tolerated, and may potentially benefit patients with statin-induced rhabdomyolysis. © 2015 Royal Australasian College of Physicians.

  1. Coenzyme O*U1*UO, Alpha-Tocopherol and Free Cholesterol in HDL and LDL Fractions

    DEFF Research Database (Denmark)

    Johansen, Kurt; Theorell, Henning; Karlsson, Jan

    1991-01-01

    Farmakologi, Alpha-tocopherol, Coenzyme Q*U1*U0, free cholesterol, LDL, Antioxidants, Lipoproteins, HDL......Farmakologi, Alpha-tocopherol, Coenzyme Q*U1*U0, free cholesterol, LDL, Antioxidants, Lipoproteins, HDL...

  2. Bioavailability of four oral Coenzyme Q formulations in healthy volunteers

    DEFF Research Database (Denmark)

    Weis, M.; Mortensen, S.A.; Rassing, M.R.

    1994-01-01

    The bioavailability of four different Coenzyme Q (CoQ) formulations was compared in ten healthy volunteers in a four-way randomised cross-over trial. The included formulations were: A hard gelatine capsule containing 100 mg of CoQ and 400 mg of Emcompress. Three soft gelatine capsules containing......Q (Bioquinon has the highest bioavailability. A difference in basic AUC and AUC after p.o.administration of CoQ was observed with respect to sex. A characteristic two peak-pattern was observed at the concentration-time profile....

  3. Synthetic biology for engineering acetyl coenzyme a metabolism in yeast

    DEFF Research Database (Denmark)

    Nielsen, Jens

    2014-01-01

    The yeast Saccharomyces cerevisiae is a widely used cell factory for the production of fuels, chemicals, and pharmaceuticals. The use of this cell factory for cost-efficient production of novel fuels and chemicals requires high yields and low by-product production. Many industrially interesting...... chemicals are biosynthesized from acetyl coenzyme A (acetyl-CoA), which serves as a central precursor metabolite in yeast. To ensure high yields in production of these chemicals, it is necessary to engineer the central carbon metabolism so that ethanol production is minimized (or eliminated) and acetyl...

  4. The complete coenzyme B12 biosynthesis gene cluster of Lactobacillus reuteri CRL 1098

    NARCIS (Netherlands)

    Santos, dos F.; Vera, J.L.; Heijden, van der R.; Valdez, G.F.; Vos, de W.M.; Sesma, F.; Hugenholtz, J.

    2008-01-01

    The coenzyme B12 production pathway in Lactobacillus reuteri has been deduced using a combination of genetic, biochemical and bioinformatics approaches. The coenzyme B12 gene cluster of Lb. reuteri CRL1098 has the unique feature of clustering together the cbi, cob and hem genes. It consists of 29

  5. Balneotherapy and coenzyme Q10 in clinical and experimental medicine.

    Science.gov (United States)

    Gvozdjakova, Anna; Kucharska, Jarmila; Sykora, L'ubomir; Singh, Ram B

    2014-01-01

    Balneotherapy or Spa therapy is used in neurological, cardiovascular, musculoskeletal, dermatological and gynecological diseases, in infertility as well as in metabolic disturbances. Beneficial effects of balneotherapy at the metabolic level is not fully understood. Authors have documented enhancement of antioxidants concentrations (coenzyme Q10- CoQ(10-OX) and alpha-tocopherol) of women with gynecological diseases by treatment with natural mineral water (Spa Lucky balneotherapy, Slovakia). In an experiment with rats, drinking of Spa Lucky mineral water decreased oxidative stress and enhanced concentrations of antioxidants CoQ(9-OX), CoQ(10-OX) in the myocardium, and alpha-tocopherol in uterus, ovaries and myocardium. Drinking of Spa Lucky water by rats stimulated myocardial mitochondrial respiration and energy production, and diminished skeletal muscle mitochondrial function. Simultaneous ingestion of coenzyme Q10 with drinking spa water returned mitochondrial parameters to the values of the control group. This pilot study helps explain the role of antioxidants, oxidative stress and mitochondrial energy production in beneficial effects of Spa Lucky balneotherapy.

  6. Purification, crystallization and preliminary X-ray analysis of 3-hydroxy-3-methylglutaryl-coenzyme A reductase of Streptococcus pneumoniae

    International Nuclear Information System (INIS)

    Zhang, Liping; Feng, Lingling; Zhou, Li; Gui, Jie; Wan, Jian; Hu, Xiaopeng

    2010-01-01

    3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase of Streptococcus pneumoniae has been cloned, overexpressed and purified to homogeneity using Ni–NTA affinity chromatography. Crystals were obtained using the hanging-drop vapour-diffusion method. Class II 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductases are potential targets for novel antibiotic development. In order to obtain a precise structural model for use in virtual screening and inhibitor design, HMG-CoA reductase of Streptococcus pneumoniae was cloned, overexpressed and purified to homogeneity using Ni–NTA affinity chromatography. Crystals were obtained using the hanging-drop vapour-diffusion method. A complete data set was collected from a single frozen crystal on a home X-ray source. The crystal diffracted to 2.3 Å resolution and belonged to the orthorhombic space group C222 1 , with unit-cell parameters a = 773.4836, b = 90.3055, c = 160.5592 Å, α = β = γ = 90°. Assuming the presence of two molecules in the asymmetric unit, the solvent content was estimated to be 54.1% (V M = 2.68 Å 3 Da −1 )

  7. Protein Engineering for Nicotinamide Coenzyme Specificity in Oxidoreductases: Attempts and Challenges.

    Science.gov (United States)

    Chánique, Andrea M; Parra, Loreto P

    2018-01-01

    Oxidoreductases are ubiquitous enzymes that catalyze an extensive range of chemical reactions with great specificity, efficiency, and selectivity. Most oxidoreductases are nicotinamide cofactor-dependent enzymes with a strong preference for NADP or NAD. Because these coenzymes differ in stability, bioavailability and costs, the enzyme preference for a specific coenzyme is an important issue for practical applications. Different approaches for the manipulation of coenzyme specificity have been reported, with different degrees of success. Here we present various attempts for the switching of nicotinamide coenzyme preference in oxidoreductases by protein engineering. This review covers 103 enzyme engineering studies from 82 articles and evaluates the accomplishments in terms of coenzyme specificity and catalytic efficiency compared to wild type enzymes of different classes. We analyzed different protein engineering strategies and related them with the degree of success in inverting the cofactor specificity. In general, catalytic activity is compromised when coenzyme specificity is reversed, however when switching from NAD to NADP, better results are obtained. In most of the cases, rational strategies were used, predominantly with loop exchange generating the best results. In general, the tendency of removing acidic residues and incorporating basic residues is the strategy of choice when trying to change specificity from NAD to NADP, and vice versa . Computational strategies and algorithms are also covered as helpful tools to guide protein engineering strategies. This mini review aims to give a general introduction to the topic, giving an overview of tools and information to work in protein engineering for the reversal of coenzyme specificity.

  8. Sodium 2-mercaptoethanesulfonate monohydrate (coenzyme M sodium salt monohydrate

    Directory of Open Access Journals (Sweden)

    Stefan Mayr

    2008-11-01

    Full Text Available The 2-thioethanesulfonate anion is the smallest known coenzyme in nature (HS–CoM and plays a key role in methanogenesis by anaerobic archaea, as well as in the oxidation of alkenes by Gram-negative and Gram-positive eubacteria. The title compound, Na+·C2H5O3S2−·H2O, is the Na+ salt of HS–CoM crystallized as the monohydrate. Six O atoms form a distorted octahedral coordination geometry around the Na atom, at distances in the range 2.312 (4–2.517 (3 Å. Two O atoms of the sulfonate group, one O atom of each of three other symmetry-related sulfonate groups plus the water O atom form the coordination environment of the Na+ ion. This arrangement forms Na–O–Na layers in the crystal structure, parallel to (100.

  9. The effect of coenzyme Q10 in statin myopathy.

    Science.gov (United States)

    Zlatohlavek, Lukas; Vrablik, Michal; Grauova, Barbora; Motykova, Eva; Ceska, Richard

    2012-01-01

    Statins significantly reduce CV morbidity and mortality. Unfortunately, one of the side effects of statins is myopathy, for which statins cannot be administered in sufficient doses or administered at all. The aim of this study was to demonstrate the effect of coenzyme Q10 in patients with statin myopathy. Twenty eight patients aged 60.6±10.7 years were monitored (18 women and 10 men) and treated with different types and doses of statin. Muscle weakness and pain was monitored using a scale of one to ten, on which patients expressed the degree of their inconvenience. Examination of muscle problems was performed prior to administration of CQ10 and after 3 and 6 months of dosing. Statistical analysis was performed using Friedman test, Annova and Students t-test. Pain decreased on average by 53.8% (pmuscle weakness by 44.4% (pmuscle pain and sensitivity statistically significantly decreased.

  10. Synthesis of carbon-14-labeled sodium palmoxirate and its coenzyme A ester

    Energy Technology Data Exchange (ETDEWEB)

    Weaner, L.E.; Hoerr, D.C.

    1986-04-01

    Synthetic procedures for the preparation of carbon-14-labeled sodium palmoxirate (TDGA), labeled either in the carboxyl position or in the tetradecyl hydrocarbon chain, are described. In addition, the synthesis of the coenzyme A ester of TDGA-14C with a specific activity of 51 mCi/mmol is reported. The coenzyme A ester was prepared by formation of the acyl chloride with oxalyl chloride followed by reaction with coenzyme A (CoA) in a borate-buffered tetrahydrofuran solution. Purification methods and analytical and stability data are reported for the compounds.

  11. Coenzyme Q 10: multiple benefits in one ingredient

    Directory of Open Access Journals (Sweden)

    Littarru Gian Paolo

    2011-03-01

    Full Text Available Coenzyme Q is a lipid molecule widely diffused in nature; in humans and other mammals it is present as coenzyme Q10. (CoQ10. The first recognized role of CoQ10 was in mitochondrial bioenergetics, where it plays a central role in the production of ATP. It is also present in other subcellular organelles, both in its oxidized and in its reduced state (ubiquinol-10. The reduced form of CoQ10 is endowed with powerful antioxidant activity: it acts as a chain-breaking antioxidant and is also capable of egenerating alpha-tocopherol, the active form of vitamin E. By these mechanisms CoQ10, together with vitamin E, protects lipoproteins from oxidation a process which bears considerable interest in preventing atherosclerosis. CoQ10 has also been found to support cardiovascular function and the latest findings indicate an active role in counteracting endothelial dysfunction, which is closely implicated in cardiovascular disease. CoQ10 also improves sperm motility, an effect which might be related both to its antioxidant and to its bioenergetic properties. Oxidative stress might be involved in neurodegenerative disease, and in migraine, two fields where the positive effects of CoQ10 have been documented. CoQ10 is synthesized by our body but is also present in food and can be taken as a nutritional supplement. The main source of industrially produced CoQ10 is yeast fermentation. The process results in CoQ10 which is identical to the naturally occurring molecule. Ubiquinol, the reduced form of CoQ10, has recently become available.

  12. Fatty Acid Synthase Inhibitor Cytotoxicity: Depletion of the Coenzyme-A Pool

    National Research Council Canada - National Science Library

    Kuhajda, Francis

    2003-01-01

    .... In light of recent data that showed a marked increase in malonyl-CoA following FAS inhibition, this grant was focused on coenzyme-A depletion as a key mechanism of action leading to cytotoxicity...

  13. Supplementation of Coenzyme Q10 among Patients with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Qiuhua Shen

    2015-05-01

    Full Text Available Type 2 diabetes mellitus (T2DM is a major cause of morbidity and mortality with ever increasing prevalence in the United States and worldwide. There is growing body of evidence suggesting that mitochondrial dysfunction secondary to oxidative stress plays a critical role in the pathogenesis of T2DM. Coenzyme Q10 is an important micronutrient acting on the electron transport chain of the mitochondria with two major functions: (1 synthesis of adenosine triphosphate (ATP; and (2 a potent antioxidant. Deficiency in coenzyme Q10 is often seen in patients with T2DM. Whether restoration of coenzyme Q10 will help alleviate oxidative stress, preserve mitochondrial function, and thus improve glycemic control in T2DM is unclear. This article reviews the relationships among oxidative stress, mitochondrial dysfunction, and T2DM and examines the evidence for potential use of coenzyme Q10 as a supplement for the treatment of T2DM.

  14. Effect of coenzyme q10 on myopathic symptoms in patients treated with statins.

    Science.gov (United States)

    Caso, Giuseppe; Kelly, Patricia; McNurlan, Margaret A; Lawson, William E

    2007-05-15

    Treatment of hypercholesterolemia with statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) is effective in the primary and secondary prevention of cardiovascular disease. However, statin use is often associated with a variety of muscle-related symptoms or myopathies. Myopathy may be related in part to statin inhibition of the endogenous synthesis of coenzyme Q10, an essential cofactor for mitochondrial energy production. The aim of this study is to determine whether coenzyme Q10 supplementation would reduce the degree of muscle pain associated with statin treatment. Patients with myopathic symptoms were randomly assigned in a double-blinded protocol to treatment with coenzyme Q10 (100 mg/day, n = 18) or vitamin E (400 IU/day, n = 14) for 30 days. Muscle pain and pain interference with daily activities were assessed before and after treatment. After a 30-day intervention, pain severity decreased by 40% (p pain interference with daily activities decreased by 38% (p pain severity (+9%, p = NS) or pain interference with daily activities (-11%, p = NS) was observed in the group treated with vitamin E. In conclusion, results suggest that coenzyme Q10 supplementation may decrease muscle pain associated with statin treatment. Thus, coenzyme Q10 supplementation may offer an alternative to stopping treatment with these vital drugs.

  15. Electron addition to alkyl cobalamins, coenzyme B12 and vitamin B12

    International Nuclear Information System (INIS)

    Rao, D.N.R.; Symons, M.C.R.

    1983-01-01

    Exposure of dilute solutions of methyl and ethyl cobalamins and coenzyme B 12 in dilute solutions (D 2 O+CD 3 OD) to 60 Co #betta#-rays at 77 K gave a single broad feature in the free-spin region assigned to electron-capture species with the excess electron largely confined to a π* corrin orbital. On warming above 77 K the methyl derivative gave a novel species with spectral features characteristic of an unpaired electron in the Co(dsub(x 2 -y 2 )) orbital. The other two substrates gave spectra due to Cosup(II)Bsub(12r) both on warming and after photolyses with visible light. The acetyl derivative gave an electron-capture species whose e.s.r. spectrum was characteristic of an electron in the Co(dsub(z 2 )) orbital, which on warming above 77 K changed to the normal Cosup(II)Bsub(12r) spectrum. The cyano derivative (vitamin B 12 ) gave electron addition into the Co(dsub(z 2 )) orbital, as evidenced by the large hyperfine coupling to 13 C from 13 CN ligands. On annealing, cyanide ions were lost irreversibly, Bsub(12r) being detected by e.s.r. spectroscopy. In contrast, the dicyano derivative on electron addition at 77 K gave a species containing only one 13 CN ligand. Hence in this case one CN - ligand was lost at 77 K, with no return of the dimethylbenzimidazole ligand. These results are discussed in terms of a new mechanism for electron-addition to alkyl cobalamins. (author)

  16. Coenzyme Q10 Supplementation Decreases Statin-Related Mild-to-Moderate Muscle Symptoms: A Randomized Clinical Study

    OpenAIRE

    Skarlovnik, Ajda; Janić, Miodrag; Lunder, Mojca; Turk, Martina; Šabovič, Mišo

    2014-01-01

    Background Statin use is frequently associated with muscle-related symptoms. Coenzyme Q10 supplementation has yielded conflicting results in decreasing statin myopathy. Herein, we tested whether coenzyme Q10 supplementation could decrease statin-associated muscular pain in a specific group of patients with mild-to-moderate muscle symptoms. Material/Methods Fifty patients treated with statins and reporting muscle pain were recruited. The Q10 group (n=25) received coenzyme Q10 supplementation o...

  17. Hormonal Influence on Coenzyme Q10 Levels in Blood Plasma

    Directory of Open Access Journals (Sweden)

    Alfredo Pontecorvi

    2011-12-01

    Full Text Available Coenzyme Q10 (CoQ10, also known as ubiquinone for its presence in all body cells, is an essential part of the cell energy-producing system. However, it is also a powerful lipophilic antioxidant protecting lipoproteins and cell membranes. Due to these two actions, CoQ10 is commonly used in clinical practice in chronic heart failure, male infertility, and neurodegenerative disease. However, it is also taken as an anti-aging substance by healthy people aiming for long-term neuroprotection and by sportsmen to improve endurance. Many hormones are known to be involved in body energy regulation, in terms of production, consumption and dissipation, and their influence on CoQ10 body content or blood values may represent an important pathophysiological mechanism. We summarize the main findings of the literature about the link between hormonal systems and circulating CoQ10 levels. In particular the role of thyroid hormones, directly involved in the regulation of energy homeostasis, is discussed. There is also a link with gonadal and adrenal hormones, partially due to the common biosynthetic pathway with CoQ10, but also to the increased oxidative stress found in hypogonadism and hypoadrenalism.

  18. Coenzyme Q10 Supplementation in Aging and Disease

    Directory of Open Access Journals (Sweden)

    Juan D. Hernández-Camacho

    2018-02-01

    Full Text Available Coenzyme Q (CoQ is an essential component of the mitochondrial electron transport chain and an antioxidant in plasma membranes and lipoproteins. It is endogenously produced in all cells by a highly regulated pathway that involves a mitochondrial multiprotein complex. Defects in either the structural and/or regulatory components of CoQ complex or in non-CoQ biosynthetic mitochondrial proteins can result in a decrease in CoQ concentration and/or an increase in oxidative stress. Besides CoQ10 deficiency syndrome and aging, there are chronic diseases in which lower levels of CoQ10 are detected in tissues and organs providing the hypothesis that CoQ10 supplementation could alleviate aging symptoms and/or retard the onset of these diseases. Here, we review the current knowledge of CoQ10 biosynthesis and primary CoQ10 deficiency syndrome, and have collected published results from clinical trials based on CoQ10 supplementation. There is evidence that supplementation positively affects mitochondrial deficiency syndrome and the symptoms of aging based mainly on improvements in bioenergetics. Cardiovascular disease and inflammation are alleviated by the antioxidant effect of CoQ10. There is a need for further studies and clinical trials involving a greater number of participants undergoing longer treatments in order to assess the benefits of CoQ10 treatment in metabolic syndrome and diabetes, neurodegenerative disorders, kidney diseases, and human fertility.

  19. Coenzyme Q10 protects hair cells against aminoglycoside.

    Directory of Open Access Journals (Sweden)

    Kazuma Sugahara

    Full Text Available It is well known that the production of free radicals is associated with sensory cell death induced by an aminoglycoside. Many researchers have reported that antioxidant reagents protect sensory cells in the inner ear, and coenzyme Q10 (CoQ10 is an antioxidant that is consumed as a health food in many countries. The purpose of this study was to investigate the role of CoQ10 in mammalian vestibular hair cell death induced by aminoglycoside. Cultured utricles of CBA/CaN mice were divided into three groups (control group, neomycin group, and neomycin + CoQ10 group. In the neomycin group, utricles were cultured with neomycin (1 mM to induce hair cell death. In the neomycin + CoQ10 group, utricles were cultured with neomycin and water-soluble CoQ10 (30-0.3 µM. Twenty-four hours after exposure to neomycin, the cultured tissues were fixed, and vestibular hair cells were labeled using an anti-calmodulin antibody. Significantly more hair cells survived in the neomycin + CoQ10 group than in the neomycin group. These data indicate that CoQ10 protects sensory hair cells against neomycin-induced death in the mammalian vestibular epithelium; therefore, CoQ10 may be useful as a protective drug in the inner ear.

  20. Determination of hydrophobic coenzyme a esters and other lipids using a biosensor comprising a modified coenzyme a- and acyl-coa binding protein (acbp)

    DEFF Research Database (Denmark)

    2002-01-01

    , food and feed preparations, tissue extracts, acyl-CoA synthetase reaction media and various laboratory conditions using a modified Coenzyme A- and acyl-CoA binding protein (ACBP) is provided. Furthermore the invention relates to a construct comprising a peptide and a signal moiety for performing...

  1. The antioxidant status of coenzyme Q10 and vitamin E in children with type 1 diabetes.

    Science.gov (United States)

    Alkholy, Usama M; Abdalmonem, Nermin; Zaki, Ahmed; Elkoumi, Mohamed A; Hashim, Mustafa I Abu; Basset, Maha A A; Salah, Hossam E

    2018-02-07

    The purpose of this study was to evaluate the antioxidant status of plasma vitamin E and plasma and intracellular coenzyme Q10 in children with type 1 diabetes. This case-control study was conducted on 72 children with type 1 diabetes and compared to 48 healthy children, who were age, sex, and ethnicity-matched. The diabetic children were divided according to their glycosylated hemoglobin (A1c %) into two groups: poor and good glycemic control groups. All children underwent full history taking, clinical examination, and laboratory measurement of complete blood count, A1c %, plasma cholesterol, triglycerides, and vitamin E levels and coenzyme Q10 levels in plasma, erythrocytes, and platelets. Children with poor glycemic control showed significantly higher plasma vitamin E, coenzyme Q10, triglycerides, low-density lipoproteins, waist circumference/height ratio, cholesterol levels, and lower high-density lipoproteins and platelet coenzyme Q10 redox status in comparison to those with good glycemic control and the control group (p<0.05). Plasma coenzyme Q10 showed a positive correlation with the duration of type 1 diabetes, triglycerides, cholesterol, vitamin E, and A1c %, and negative correlation with the age of the diabetic group (p<0.05). The platelet redox status showed a negative correlation with the A1c % levels (r=-0.31; p=0.022) and the duration of type 1 diabetes (r=-0.35, p=0.012). Patients with type 1 diabetes, especially poorly controlled, had elevation of plasma vitamin E and coenzyme Q10 levels and decreased platelet redox status of coenzyme Q10, which may be an indicator of increased oxidative stress. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  2. Active-site-directed inhibition of 3-hydroxy-3-methylglutaryl coenzyme A synthase by 3-chloropropionyl coenzyme A

    International Nuclear Information System (INIS)

    Miziorko, H.M.; Behnke, C.E.

    1985-01-01

    3-Chloropropionyl coenzyme A (3-chloropropionyl-CoA) irreversibly inhibits avian liver 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase). Enzyme inactivation follows pseudo-first-order kinetics and is retarded in the presence of substrates, suggesting that covalent labeling occurs at the active site. A typical rate saturation effect is observed when inactivation kinetics are measured as a function of 3-chloropropionyl-CoA concentration. These data indicate a Ki = 15 microM for the inhibitor and a limiting kinact = 0.31 min-1. [1- 14 C]-3-Chloropropionyl-CoA binds covalently to the enzyme with a stoichiometry (0.7 per site) similar to that measured for acetylation of the enzyme by acetyl-CoA. While the acetylated enzyme formed upon incubation of HMG-CoA synthase with acetyl-CoA is labile to performic acid oxidation, the adduct formed upon 3-chloropropionyl-CoA inactivation is stable to such treatment. Therefore, such an adduct cannot solely involve a thio ester linkage. Exhaustive Pronase digestion of [ 14 C]-3-chloropropionyl-CoA-labeled enzyme produces a radioactive compound which cochromatographs with authentic carboxyethylcysteine using reverse-phase/ion-pairing high-pressure liquid chromatography and both silica and cellulose thin-layer chromatography systems. This suggests that enzyme inactivation is due to alkylation of an active-site cysteine residue

  3. The Antioxidant Status and Concentrations of Coenzyme Q10 and Vitamin E in Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Chi-Hua Yen

    2013-01-01

    Full Text Available The purpose of this study was to investigate the levels of coenzyme Q10 and vitamin E and the antioxidant status in subjects with metabolic syndrome (MS. Subjects with MS (n=72 were included according to the criteria for MS. The non-MS group (n=105 was comprised of healthy individuals with normal blood biochemical values. The plasma coenzyme Q10, vitamin E concentrations, lipid profiles, and antioxidant enzymes levels (catalase, superoxide dismutase, and glutathione peroxidase were measured. The subjects with MS had significantly higher concentrations of plasma coenzyme Q10 and vitamin E than those in the non-MS group, but these differences were not significant after being normalized for triglyceride level. The levels of antioxidant enzymes were significantly lower in the MS group than in the non-MS group. The subjects with the higher antioxidant enzymes activities had significant reductions in the risk of MS (P<0.01 after being adjusted for coenzyme Q10 and vitamin E. In conclusion, the subjects with MS might be under higher oxidative stress resulting in low levels of antioxidant enzyme activities. A higher level of antioxidant enzymes activities was significantly associated with a reduction in the risk of MS independent of the levels of coenzyme Q10 and vitamin E.

  4. Altered fatty acid metabolism and reduced stearoyl-coenzyme a desaturase activity in asthma.

    Science.gov (United States)

    Rodriguez-Perez, N; Schiavi, E; Frei, R; Ferstl, R; Wawrzyniak, P; Smolinska, S; Sokolowska, M; Sievi, N A; Kohler, M; Schmid-Grendelmeier, P; Michalovich, D; Simpson, K D; Hessel, E M; Jutel, M; Martin-Fontecha, M; Palomares, O; Akdis, C A; O'Mahony, L

    2017-11-01

    Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely underexplored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and nonobese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models. Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS. Changes in stearoyl-coenzyme A desaturase (SCD) expression and activity were evaluated in the ovalbumin (OVA) and house dust mite (HDM) murine models. Primary human bronchial epithelial cells from asthma patients and controls were evaluated for SCD expression and activity. The serum desaturation index (an indirect measure of SCD) was significantly reduced in nonobese asthma patients and in the OVA murine model. SCD1 gene expression was significantly reduced within the lungs following OVA or HDM challenge. Inhibition of SCD in mice promoted airway hyper-responsiveness. SCD1 expression was suppressed in bronchial epithelial cells from asthma patients. IL-4 and IL-13 reduced epithelial cell SCD1 expression. Inhibition of SCD reduced surfactant protein C expression and suppressed rhinovirus-induced IP-10 secretion, which was associated with increased viral titers. This is the first study to demonstrate decreased fatty acid desaturase activity in humans with asthma. Experimental models in mice and human epithelial cells suggest that inhibition of desaturase activity leads to airway hyper-responsiveness and reduced antiviral defense. SCD may represent a new target for therapeutic intervention in asthma patients. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  5. Promotion of growth by Coenzyme Q10 is linked to gene expression in C. elegans.

    Science.gov (United States)

    Fischer, Alexandra; Niklowitz, Petra; Menke, Thomas; Döring, Frank

    2014-10-03

    Coenzyme Q (CoQ, ubiquinone) is an essential component of the respiratory chain, a cofactor of pyrimidine biosynthesis and acts as an antioxidant in extra mitochondrial membranes. More recently CoQ has been identified as a modulator of apoptosis, inflammation and gene expression. CoQ deficient Caenorhabditis elegans clk-1 mutants show several phenotypes including a delayed postembryonic growth. Using wild type and two clk-1 mutants, here we established an experimental set-up to study the consequences of endogenous CoQ deficiency or exogenous CoQ supply on gene expression and growth. We found that a deficiency of endogenous CoQ synthesis down-regulates a cluster of genes that are important for growth (i.e., RNA polymerase II, eukaryotic initiation factor) and up-regulates oxidation reactions (i.e., cytochrome P450, superoxide dismutase) and protein interactions (i.e., F-Box proteins). Exogenous CoQ supply partially restores the expression of these genes as well as the growth retardation of CoQ deficient clk-1 mutants. On the other hand exogenous CoQ supply does not alter the expression of a further sub-set of genes. These genes are involved in metabolism (i.e., succinate dehydrogenase complex), cell signalling or synthesis of lectins. Thus, our work provides a comprehensive overview of genes which can be modulated in their expression by endogenous or exogenous CoQ. As growth retardation in CoQ deficiency is linked to the gene expression profile we suggest that CoQ promotes growth via gene expression. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Very long-chain acyl-coenzyme A dehydrogenase deficiency

    Directory of Open Access Journals (Sweden)

    A. V. Degtyareva

    2014-01-01

    Full Text Available The paper describes a case of a baby with a severe infant form of very long-chain acyl-coenzyme A dehydrogenase deficiency, a very rare genetic disorder. The basis for the disease is a disorder of mitochondrial β-oxidation of long-chain fatty acids. Accumulation of acyl-CoA-derived fatty acids causes a toxic effect on the myocardium and cardiac conduction system, liver, skeletal muscles, and other organs. The development of hypoglycemia is typical. Treatment in the acute period involves the immediately ceased delivery of long-chain triglycerides, the provision of the body with medium-chain triglycerides, and the correction of glycemia. In our observation the baby was born at term with a satisfactory condition in a family with a poor history (the first baby had suddenly died at the age of 3,5 months. The disease manifested itself as bradyarrhythmia and cardiac arrest on day 2 of life. The clinical symptom complex also included hepatomegalia, hypoglycemic episodes, lactate acidosis, and elevated blood levels of cytolytic enzymes and creatine phosphokinase. The diagnosis was suspected on the basis of the high blood values of acylcarnitines (primarily C14:1 and verified by a molecular genetic examination. Syndrome therapy and dietotherapy resulted in the abolishment of the abnormality. At the age of 2 years of life, the infant’s physical, motor, mental, and speech development corresponded to his age although he had mild right-sided hemiparesis. Thus, timely therapy determines the favorable prognosis of the disease even in its severe infant forms. 

  7. Biochemistry of methyl-coenzyme M reductase: the nickel metalloenzyme that catalyzes the final step in synthesis and the first step in anaerobic oxidation of the greenhouse gas methane.

    Science.gov (United States)

    Ragsdale, Stephen W

    2014-01-01

    Methane, the major component of natural gas, has been in use in human civilization since ancient times as a source of fuel and light. Methanogens are responsible for synthesis of most of the methane found on Earth. The enzyme responsible for catalyzing the chemical step of methanogenesis is methyl-coenzyme M reductase (MCR), a nickel enzyme that contains a tetrapyrrole cofactor called coenzyme F430, which can traverse the Ni(I), (II), and (III) oxidation states. MCR and methanogens are also involved in anaerobic methane oxidation. This review describes structural, kinetic, and computational studies aimed at elucidating the mechanism of MCR. Such studies are expected to impact the many ramifications of methane in our society and environment, including energy production and greenhouse gas warming.

  8. Continuous recording of long-chain acyl-coenzyme A synthetase activity using fluorescently labeled bovine serum albumin

    DEFF Research Database (Denmark)

    Demant, Erland J.F.; Nystrøm, Birthe T.

    2001-01-01

    acyl-Coenzyme A, synthetase, activity assay, fluorescence recording, fatty acid probe, serum albumin, hydroxycoumarin, detergent, micelles, Pseudomonas fragi, rat liver microsomes......acyl-Coenzyme A, synthetase, activity assay, fluorescence recording, fatty acid probe, serum albumin, hydroxycoumarin, detergent, micelles, Pseudomonas fragi, rat liver microsomes...

  9. Synthesis of coenzyme A and nicotineamide-adenine dinucleotide labelled with tritium

    International Nuclear Information System (INIS)

    Sidorov, G.V.; Zverkov, Yu.B.; Myasoedov, N.F.

    1999-01-01

    Isotopic exchange in solution with tritium water and with gaseous tritium and solid-phase reaction of isotopic exchange of NAD with tritium were investigated. For synthesis of labelled with tritium coenzyme A solid-phase reaction of isotopic exchange with gaseous tritium was used. It was determined that 98% of tritium was contained in nicotineamide part of molecule of NAD. In the case of coenzyme A studying of intramolecular distribution of tritium demonstrated that 90% of tritium were localized in adenine fragment [ru

  10. Modeling the reactions catalyzed by coenzyme B12-dependent enzymes.

    Science.gov (United States)

    Sandala, Gregory M; Smith, David M; Radom, Leo

    2010-05-18

    Enzymes accelerate chemical reactions with an exceptional selectivity that makes life itself possible. Understanding the factors responsible for this efficient catalysis is of utmost importance in our quest to harness the tremendous power of enzymes. Computational chemistry has emerged as an important adjunct to experimental chemistry and biochemistry in this regard, because it provides detailed insights into the relationship between structure and function in a systematic and straightforward manner. In this Account, we highlight our recent high-level theoretical investigations toward this end in studying the radical-based reactions catalyzed by enzymes dependent on coenzyme B(12) (or adenosylcobalamin, AdoCbl). In addition to their fundamental position in biology, the AdoCbl-dependent enzymes represent a valuable framework within which to understand Nature's method of efficiently handling high-energy species to execute very specific reactions. The AdoCbl-mediated reactions are characterized by the interchange of a hydrogen atom and a functional group on adjacent carbon atoms. Our calculations are consistent with the conclusion that the main role of AdoCbl is to provide a source of radicals, thus moving the 1,2-rearrangements onto the radical potential energy surface. Our studies also show that the radical rearrangement step is facilitated by partial proton transfer involving the substrate. Specifically, we observe that the energy requirements for radical rearrangement are reduced dramatically with appropriate partial protonation or partial deprotonation or sometimes (synergistically) both. Such interactions are particularly relevant to enzyme catalysis, because it is likely that the local amino acid environment in the active site of an enzyme can function in this capacity through hydrogen bonding. Finally, our calculations indicate that the intervention of a very stable radical along the reaction pathway may inactivate the enzyme, demonstrating that sustained

  11. A coenzyme-independent decarboxylase/oxygenase cascade for the efficient synthesis of vanillin.

    Science.gov (United States)

    Furuya, Toshiki; Miura, Misa; Kino, Kuniki

    2014-10-13

    Vanillin is one of the most widely used flavor compounds in the world as well as a promising versatile building block. The biotechnological production of vanillin from plant-derived ferulic acid has attracted much attention as a new alternative to chemical synthesis. One limitation of the known metabolic pathway to vanillin is its requirement for expensive coenzymes. Here, we developed a novel route to vanillin from ferulic acid that does not require any coenzymes. This artificial pathway consists of a coenzyme-independent decarboxylase and a coenzyme-independent oxygenase. When Escherichia coli cells harboring the decarboxylase/oxygenase cascade were incubated with ferulic acid, the cells efficiently synthesized vanillin (8.0 mM, 1.2 g L(-1) ) via 4-vinylguaiacol in one pot, without the generation of any detectable aromatic by-products. The efficient method described here might be applicable to the synthesis of other high-value chemicals from plant-derived aromatics. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Concentrations in beef and lamb of taurine, carnosine, coenzyme Q(10), and creatine.

    Science.gov (United States)

    Purchas, R W; Rutherfurd, S M; Pearce, P D; Vather, R; Wilkinson, B H P

    2004-03-01

    Levels of taurine, carnosine, coenzyme Q(10), and creatine were measured in beef liver and several muscles of beef and lamb and in cooked and uncooked meat. The amino acid taurine has numerous biological functions, the dipeptide carnosine is a buffer as well as an antioxidant, coenzyme Q(10) is also an antioxidant present within mitochondria, and creatine along with creatine phosphate is involved with energy metabolism in muscle. Large differences were shown for all compounds between beef cheek muscle (predominantly red fibres) and beef semitendinosus muscle (mainly white fibres), with cheek muscle containing 9.9 times as much taurine, and 3.2 times as much coenzyme Q(10), but only 65% as much creatine and 9% as much carnosine. Levels in lamb relative to beef semitendinosus muscles were higher for taurine but slightly lower for carnosine, coenzyme Q(10) and creatine. Values for all the compounds varied significantly between eight lamb muscles, possibly due in part to differences in the proportion of muscle fibre types. Slow cooking (90 min at 70 °C) of lamb longissimus and semimembranosus muscles led to significant reductions in the content of taurine, carnosine, and creatine (Plamb, but that these levels vary between muscles, between animals, and with cooking.

  13. Plasma coenzyme Q10 concentrations are not decreased in male patients with coronary atherosclerosis

    NARCIS (Netherlands)

    Vijver, L.P.L. van de; Weber, C.; Kardinaal, A.F.M.; Grobbee, D.E.; Princen, H.M.G.; Poppel, G. van

    1999-01-01

    Coenzyme Q10 (CoQ10) is an important mitochondrial electron transfer component and has been postulated to function as a powerful antioxidant protecting LDL from oxidative damage. It could thus reduce the risk of cardiovascular disease. Thus far, beneficial effects of supplementation with CoQ10 have

  14. Effects of ubiquinone (coenzyme Q10) on myopathy in statin users.

    NARCIS (Netherlands)

    Schaars, C.F.; Stalenhoef, A.F.H.

    2008-01-01

    PURPOSE OF REVIEW: Statins are associated with muscle complaints, including myositis. The mechanism through which statin use causes muscle toxicity is unknown. One of the theories is that statin therapy reduces coenzyme Q10 levels in muscle mitochondria, which leads to muscle injury and myopathy.

  15. Decreased coenzyme Q10 concentration in plasma of children with cystic fibrosis

    NARCIS (Netherlands)

    Oudshoorn, J.H.; Lecluse, A.L.Y.; Berg, R. van den; Vaes, W.H.J.; Laag, J. van der; Houwen, R.H.J.

    2006-01-01

    OBJECTIVES: Coenzyme Q10 (CoQ10) is an effective lipophilic antioxidant and protects against lipid peroxidation by scavenging radicals. Patients with cystic fibrosis generally have fat malabsorption; thus, we hypothesized that overall plasma CoQ10 concentration in pediatric patients with cystic

  16. A possible prebiotic synthesis of pantetheine, a precursor to coenzyme A

    Science.gov (United States)

    Keefe, A. D.; Newton, G. L.; Miller, S. L.

    1995-01-01

    The involvement of coenzyme A in many enzyme reactions suggests that it acted in this capacity very early in the development of life on Earth. Particularly relevant in this regard is its role in the activation of amino acids and hydroxy acids in the biosynthesis of some peptide antibiotics--a mechanism of peptide synthesis that forms the basis for the proposal that a thioester world could have preceded the RNA world. The components of coenzyme A have been shown to be probable prebiotic compounds: beta-alanine, pantoyl lactone and cysteamine and possibly adenosine. We show here that the pantetheine moiety of coenzyme A (which also occurs in a number of enzymes) can be synthesized in yields of several per cent by heating pantoyl lactone, beta-alanine and cysteamine at temperatures as low as 40 degrees C. These components are extremely soluble and so would have been preferentially concentrated in evaporating bodies of water, for example on beaches and at lagoon margins. Our results show that amide bonds can be formed at temperatures as low as 40 degrees C, and provide circumstantial support for the suggestion that pantetheine and coenzyme A were important in the earliest metabolic systems.

  17. Coenzyme protection of lactic dehydrogenase against inactivation by gamma-rays

    International Nuclear Information System (INIS)

    Saito, M.

    1978-01-01

    A comparison has been made of the radiation sensitivities of the ternary complexes, oxamate-LDH-NADH and pyruvate-LDH-NAD with those of free LDH molecules and the intermediate binary complexes LDH-NAD and LDH-NADH. The enzyme solutions were 60 Co γirradiated and the rate of pyruvate reduction then measured. At doses of more than 10 krad the coenzymes afforded considerable protection to LDH against inactivation, and the dose-effect curves deviated from the curve for the unprotected enzyme, implying very specific protection. Coenzyme protection for a 30 krad dose at various concentrations of NAD and NADH reached a saturation level at about 4.0 x 10 -4 M for both NAD and NADH; protection by pyruvate alone was slight in comparison. Pyruvate and NAD (or oxamate and NADH) together at 1.0 x 10 -3 M protected the enzyme in a cooperative way. The results suggest that the major events of protection occur on the substrate and coenzyme binding sites, and support the view that coenzyme binding protects the enzyme by altering its conformation. (U.K.)

  18. Induction of Cytosolic Acetyl-Coenzyme A Carboxylase in Pea Leaves by Ultraviolet-B Irradiation

    OpenAIRE

    Tomokazu, Konishi; Takahiro, Kamoi; Ryuichi, Matsuno; Yukiko, Sasaki; Department of Food Science and Technology, Faculty of Agriculture, Kyoto University:(Present)Laboratory of Molecular Genetics, Biotechnology Institute, Akita Prefectural College of Agriculture; Department of Food Science and Technology, Faculty of Agriculture, Kyoto University; Department of Food Science and Technology, Faculty of Agriculture, Kyoto University; Department of Food Science and Technology, Faculty of Agriculture, Kyoto University:(Present)Laboratory of Plant Molecular Biology, School of Agricultural Sciences, Nagoya University

    1996-01-01

    Levels of subunits of two acetyl-coenzyme A carboxylases were high in small leaves of Pisum sativum, decreased with growth, and remained constant in fully expanded leaves. Irradiation of fully expanded leaves induced the cytosolic isozyme only. This result suggests a key role for the cytosolic enzyme in protection against UV-B.

  19. Coenzyme Q blocks biochemical but not receptor-mediated apoptosis by increasing mitochondrial antioxidant protection

    Czech Academy of Sciences Publication Activity Database

    Alleva, R.; Tomasetti, M.; Anděra, Ladislav; Gellert, N.; Borghi, B.; Weber, C.; Murphy, M. P.; Neužil, J.

    2001-01-01

    Roč. 503, č. 1 (2001), s. 46-50 ISSN 0014-5793 R&D Projects: GA ČR GA301/99/0350 Institutional research plan: CEZ:AV0Z5052915 Keywords : coenzyme Q * apoptosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.644, year: 2001

  20. Coenzyme B12 model studies: Equilibrium constants for the pH ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences; Volume 114; Issue 1. Coenzyme B12 model studies: Equilibrium constants for the H-dependent axial ligation of benzyl(aquo)cobaloxime by various N- and S-donor ligands. D Sudarshan Reddy N Ravi Kumar Reddy V Sridhar S Satyanarayana. Inorganic and Analytical ...

  1. A STD-NMR Study of the Interaction of the Anabaena Ferredoxin-NADP+ Reductase with the Coenzyme

    Directory of Open Access Journals (Sweden)

    Lara V. Antonini

    2014-01-01

    Full Text Available Ferredoxin-NADP+ reductase (FNR catalyzes the electron transfer from ferredoxin to NADP+ via its flavin FAD cofactor. To get further insights in the architecture of the transient complexes produced during the hydride transfer event between the enzyme and the NADP+ coenzyme we have applied NMR spectroscopy using Saturation Transfer Difference (STD techniques to analyze the interaction between FNRox and the oxidized state of its NADP+ coenzyme. We have found that STD NMR, together with the use of selected mutations on FNR and of the non-FNR reacting coenzyme analogue NAD+, are appropriate tools to provide further information about the the interaction epitope.

  2. Antioxidant vitamins C, E and coenzyme Q10 vs Dexamethasone: comparisons of their effects in pulmonary contusion model

    Directory of Open Access Journals (Sweden)

    Gokce Mertol

    2012-09-01

    Full Text Available Abstract Background The goal of our study is to evaluate the effects of antioxidant vitamins (vitamin C and E, Coenzyme Q10 (CoQ10 and dexamethasone (Dxm in experimental rat models with pulmonary contusion (PC. Methods Rats were randomly divided into six groups. Except for the control, all subgroups had a moderate pulmonary contusion. Animals in the group I and group II received intraperitoneal saline, group III received 10mg.kg-1 CoQ10 group IV received 100mg.kg-1 vitamin C, group V received 150mg.kg-1 vitamin E, and group VI received 10mg.kg-1 Dxm. Blood gas analysis, serum nitric oxide (NO and malondialdehyde (MDA levels as well as superoxide dismutase (SOD activity assays, bronchoalveolar lavage (BAL fluid and histopathological examination were performed. Results Administration of CoQ10 resulted in a significant increase in PaO2 values compared with the group I (p = 0.004. Levels of plasma MDA in group II were significantly higher than those in the group I (p = 0.01. Early administration of vitamin C, CoQ10, and Dxm significantly decreased the levels of MDA (p = 0.01. Lung contusion due to blunt trauma significantly decreased SOD activities in rat lung tissue compared with group I (p = 0.01. SOD levels were significantly elevated in animals treated with CoQ10, Vitamin E, or Dxm compared with group II (p = 0.01. Conclusions In our study, CoQ10, vitamin C, vitamin E and Dxm had a protective effect on the biochemical and histopathological outcome of PC after experimental blunt thorax trauma.

  3. Thermophilic Coenzyme B12-Dependent Acyl Coenzyme A (CoA) Mutase from Kyrpidia tusciae DSM 2912 Preferentially Catalyzes Isomerization of (R)-3-Hydroxybutyryl-CoA and 2-Hydroxyisobutyryl-CoA.

    Science.gov (United States)

    Weichler, Maria-Teresa; Kurteva-Yaneva, Nadya; Przybylski, Denise; Schuster, Judith; Müller, Roland H; Harms, Hauke; Rohwerder, Thore

    2015-07-01

    The recent discovery of a coenzyme B12-dependent acyl-coenzyme A (acyl-CoA) mutase isomerizing 3-hydroxybutyryl- and 2-hydroxyisobutyryl-CoA in the mesophilic bacterium Aquincola tertiaricarbonis L108 (N. Yaneva, J. Schuster, F. Schäfer, V. Lede, D. Przybylski, T. Paproth, H. Harms, R. H. Müller, and T. Rohwerder, J Biol Chem 287:15502-15511, 2012, http://dx.doi.org/10.1074/jbc.M111.314690) could pave the way for a complete biosynthesis route to the building block chemical 2-hydroxyisobutyric acid from renewable carbon. However, the enzyme catalyzes only the conversion of the stereoisomer (S)-3-hydroxybutyryl-CoA at reasonable rates, which seriously hampers an efficient combination of mutase and well-established bacterial poly-(R)-3-hydroxybutyrate (PHB) overflow metabolism. Here, we characterize a new 2-hydroxyisobutyryl-CoA mutase found in the thermophilic knallgas bacterium Kyrpidia tusciae DSM 2912. Reconstituted mutase subunits revealed highest activity at 55°C. Surprisingly, already at 30°C, isomerization of (R)-3-hydroxybutyryl-CoA was about 7,000 times more efficient than with the mutase from strain L108. The most striking structural difference between the two mutases, likely determining stereospecificity, is a replacement of active-site residue Asp found in strain L108 at position 117 with Val in the enzyme from strain DSM 2912, resulting in a reversed polarity at this binding site. Overall sequence comparison indicates that both enzymes descended from different prokaryotic thermophilic methylmalonyl-CoA mutases. Concomitant expression of PHB enzymes delivering (R)-3-hydroxybutyryl-CoA (beta-ketothiolase PhaA and acetoacetyl-CoA reductase PhaB from Cupriavidus necator) with the new mutase in Escherichia coli JM109 and BL21 strains incubated on gluconic acid at 37°C led to the production of 2-hydroxyisobutyric acid at maximal titers of 0.7 mM. Measures to improve production in E. coli, such as coexpression of the chaperone MeaH and repression of

  4. Coenzyme Q-responsive Leigh's encephalopathy in two sisters.

    NARCIS (Netherlands)

    Maldergem, L. van; Trijbels, J.M.F.; Mauro, S. Di; Sindelar, P.J.; Musumeci, O.; Janssen, A.J.M.; Delberghe, X.; Martin, J.J.; Gillerot, Y.

    2002-01-01

    A 31-year-old woman had encephalopathy, growth retardation, infantilism, ataxia, deafness, lactic acidosis, and increased signals of caudate and putamen on brain magnetic resonance imaging. Muscle biochemistry showed succinate:cytochrome c oxidoreductase (complex II-III) deficiency. Both clinical

  5. Compound Heterozygous Inheritance of Mutations in Coenzyme Q8A Results in Autosomal Recessive Cerebellar Ataxia and Coenzyme Q10 Deficiency in a Female Sib-Pair.

    Science.gov (United States)

    Jacobsen, Jessie C; Whitford, Whitney; Swan, Brendan; Taylor, Juliet; Love, Donald R; Hill, Rosamund; Molyneux, Sarah; George, Peter M; Mackay, Richard; Robertson, Stephen P; Snell, Russell G; Lehnert, Klaus

    2017-11-21

    Autosomal recessive ataxias are characterised by a fundamental loss in coordination of gait with associated atrophy of the cerebellum. There is significant clinical and genetic heterogeneity amongst inherited ataxias; however, an early molecular diagnosis is essential with low-risk treatments available for some of these conditions. We describe two female siblings who presented early in life with unsteady gait and cerebellar atrophy. Whole exome sequencing revealed compound heterozygous inheritance of two pathogenic mutations (p.Leu277Pro, c.1506+1G>A) in the coenzyme Q8A gene (COQ8A), a gene central to biosynthesis of coenzyme Q (CoQ). The paternally derived p.Leu277Pro mutation is predicted to disrupt a conserved motif in the substrate-binding pocket of the protein, resulting in inhibition of CoQ 10 production. The maternal c.1506+1G>A mutation destroys a canonical splice donor site in exon 12 affecting transcript processing and subsequent protein translation. Mutations in this gene can result in primary coenzyme Q 10 deficiency type 4, which is characterized by childhood onset of cerebellar ataxia and exercise intolerance, both of which were observed in this sib-pair. Muscle biopsies revealed unequivocally low levels of CoQ 10, and the siblings were subsequently established on a therapeutic dose of CoQ 10 with distinct clinical evidence of improvement after 1 year of treatment. This case emphasises the importance of an early and accurate molecular diagnosis for suspected inherited ataxias, particularly given the availability of approved treatments for some subtypes.

  6. Exogenous coenzyme Q10 modulates MMP-2 activity in MCF-7 cell line as a breast cancer cellular model

    Directory of Open Access Journals (Sweden)

    Mirmiranpour Hossein

    2010-11-01

    Full Text Available Abstract Background/Aims Matrix Metalloproteinases 2 is a key molecule in cellular invasion and metastasis. Mitochondrial ROS has been established as a mediator of MMP activity. Coenzyme Q10 contributes to intracellular ROS regulation. Coenzyme Q10 beneficial effects on cancer are still in controversy but there are indications of Coenzyme Q10 complementing effect on tamoxifen receiving breast cancer patients. Methods In this study we aimed to investigate the correlation of the effects of co-incubation of coenzyme Q10 and N-acetyl-L-cysteine (NAC on intracellular H2O2 content and Matrix Metalloproteinase 2 (MMP-2 activity in MCF-7 cell line. Results and Discussion Our experiment was designed to assess the effect in a time and dose related manner. Gelatin zymography and Flowcytometric measurement of H2O2 by 2'7',-dichlorofluorescin-diacetate probe were employed. The results showed that both coenzyme Q10 and N-acetyl-L-cysteine reduce MMP-2 activity along with the pro-oxidant capacity of the MCF-7 cell in a dose proportionate manner. Conclusions Collectively, the present study highlights the significance of Coenzyme Q10 effect on the cell invasion/metastasis effecter molecules.

  7. Electron addition to alkyl cobalamins, coenzyme B/sub 12/ and vitamin B/sub 12/. [Gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Rao, D N.R.; Symons, M C.R. [Leicester Univ. (UK). Dept. of Chemistry

    1983-01-01

    Exposure of dilute solutions of methyl and ethyl cobalamins and coenzyme B/sub 12/ in dilute solutions (D/sub 2/O+CD/sub 3/OD) to /sup 60/Co ..gamma..-rays at 77 K gave a single broad feature in the free-spin region assigned to electron-capture species with the excess electron largely confined to a ..pi..* corrin orbital. On warming above 77 K the methyl derivative gave a novel species with spectral features characteristic of an unpaired electron in the Co(dsub(x/sup 2/-y/sup 2/)) orbital. The other two substrates gave spectra due to Cosup(II)Bsub(12r) both on warming and after photolyses with visible light. The acetyl derivative gave an electron-capture species whose e.s.r. spectrum was characteristic of an electron in the Co(dsub(z/sup 2/)) orbital, which on warming above 77 K changed to the normal Cosup(II)Bsub(12r) spectrum. The cyano derivative (vitamin B/sub 12/) gave electron addition into the Co(dsub(z/sup 2/)) orbital, as evidenced by the large hyperfine coupling to /sup 13/C from /sup 13/CN ligands. On annealing, cyanide ions were lost irreversibly, Bsub(12r) being detected by e.s.r. spectroscopy. In contrast, the dicyano derivative on electron addition at 77 K gave a species containing only one /sup 13/CN ligand. Hence in this case one CN/sup -/ ligand was lost at 77 K, with no return of the dimethylbenzimidazole ligand. These results are discussed in terms of a new mechanism for electron-addition to alkyl cobalamins.

  8. Coenzyme Q10 defects may be associated with a deficiency of Q10-independent mitochondrial respiratory chain complexes

    Directory of Open Access Journals (Sweden)

    Konstantina Fragaki

    Full Text Available BACKGROUND: Coenzyme Q10 (CoQ10 or ubiquinone deficiency can be due either to mutations in genes involved in CoQ10 biosynthesis pathway, or to mutations in genes unrelated to CoQ10 biosynthesis. CoQ10 defect is the only oxidative phosphorylation disorder that can be clinically improved after oral CoQ10 supplementation. Thus, early diagnosis, first evoked by mitochondrial respiratory chain (MRC spectrophotometric analysis, then confirmed by direct measurement of CoQ10 levels, is of critical importance to prevent irreversible damage in organs such as the kidney and the central nervous system. It is widely reported that CoQ10 deficient patients present decreased quinone-dependent activities (segments I + III or G3P + III and II + III while MRC activities of complexes I, II, III, IV and V are normal. We previously suggested that CoQ10 defect may be associated with a deficiency of CoQ10-independent MRC complexes. The aim of this study was to verify this hypothesis in order to improve the diagnosis of this disease. RESULTS: To determine whether CoQ10 defect could be associated with MRC deficiency, we quantified CoQ10 by LC-MSMS in a cohort of 18 patients presenting CoQ10-dependent deficiency associated with MRC defect. We found decreased levels of CoQ10 in eight patients out of 18 (45 %, thus confirming CoQ10 disease. CONCLUSIONS: Our study shows that CoQ10 defect can be associated with MRC deficiency. This could be of major importance in clinical practice for the diagnosis of a disease that can be improved by CoQ10 supplementation.

  9. Enzymic Dehalogenation of 4-Chlorobenzoyl Coenzyme A in Acinetobacter sp. Strain 4-CB1

    OpenAIRE

    Copley, Shelley D.; Crooks, Gwen P.

    1992-01-01

    4-Chlorobenzoate degradation in cell extracts of Acinetobacter sp. strain 4-CB1 occurs by initial synthesis of 4-chlorobenzoyl coenzyme A (4-chlorobenzoyl CoA) from 4-chlorobenzoate, CoA, and ATP. 4-Chlorobenzoyl CoA is dehalogenated to 4-hydroxybenzoyl CoA. Following the dehalogenation reaction, 4-hydroxybenzoyl CoA is hydrolyzed to 4-hydroxybenzoate and CoA. Possible roles for the CoA moiety in the dehalogenation reaction are discussed.

  10. Enzymic Dehalogenation of 4-Chlorobenzoyl Coenzyme A in Acinetobacter sp. Strain 4-CB1

    Science.gov (United States)

    Copley, Shelley D.; Crooks, Gwen P.

    1992-01-01

    4-Chlorobenzoate degradation in cell extracts of Acinetobacter sp. strain 4-CB1 occurs by initial synthesis of 4-chlorobenzoyl coenzyme A (4-chlorobenzoyl CoA) from 4-chlorobenzoate, CoA, and ATP. 4-Chlorobenzoyl CoA is dehalogenated to 4-hydroxybenzoyl CoA. Following the dehalogenation reaction, 4-hydroxybenzoyl CoA is hydrolyzed to 4-hydroxybenzoate and CoA. Possible roles for the CoA moiety in the dehalogenation reaction are discussed. PMID:16348702

  11. Metal plasmon-coupled fluorescence imaging and label free coenzyme detection in cells

    International Nuclear Information System (INIS)

    Zhang, Jian; Fu, Yi; Li, Ge; Zhao, Richard Y.

    2012-01-01

    Highlights: ► Metal nanoparticle for fluorescence cell imaging. ► Non-invasive emission detection of coenzyme in cell on time-resolved confocal microscope. ► Near-field interaction of flavin adenine dinucleotide with silver substrate. ► Isolation of emissions by coenzymes from cellular autofluorescence on fluorescence cell imaging. -- Abstract: Flavin adenine dinucleotide (FAD) is a key metabolite in cellular energy conversion. Flavin can also bind with some enzymes in the metabolic pathway and the binding sites may be changed due to the disease progression. Thus, there is interest on studying its expression level, distribution, and redox state within the cells. FAD is naturally fluorescent, but it has a modest extinction coefficient and quantum yield. Hence the intrinsic emission from FAD is generally too weak to be isolated distinctly from the cellular backgrounds in fluorescence cell imaging. In this article, the metal nanostructures on the glass coverslips were used as substrates to measure FAD in cells. Particulate silver films were fabricated with an optical resonance near the absorption and the emission wavelengths of FAD which can lead to efficient coupling interactions. As a result, the emission intensity and quantum yield by FAD were greatly increased and the lifetime was dramatically shortened resulting in less interference from the longer lived cellular background. This feature may overcome the technical limits that hinder the direct observation of intrinsically fluorescent coenzymes in the cells by fluorescence microscopy. Fluorescence cell imaging on the metallic particle substrates may provide a non-invasive strategy for collecting the information of coenzymes in cells.

  12. Metal plasmon-coupled fluorescence imaging and label free coenzyme detection in cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jian, E-mail: jian@cfs.bioment.umaryland.edu [Center for Fluorescence Spectroscopy, University of Maryland School of Medicine, Department of Biochemistry and Molecular Biology, 725 West Lombard Street, Baltimore, MD 21201 (United States); Fu, Yi [Center for Fluorescence Spectroscopy, University of Maryland School of Medicine, Department of Biochemistry and Molecular Biology, 725 West Lombard Street, Baltimore, MD 21201 (United States); Li, Ge [Division of Molecular Pathology, Department of Pathology, University of Maryland School of Medicine, 10 South Pine Street, Baltimore, MD 21201 (United States); Zhao, Richard Y. [Division of Molecular Pathology, Department of Pathology, University of Maryland School of Medicine, 10 South Pine Street, Baltimore, MD 21201 (United States); Department of Microbiology-Immunology, University of Maryland School of Medicine, 10 South Pine Street, Baltimore, MD 21201 (United States); Institute of Human Virology, University of Maryland School of Medicine, 10 South Pine Street, Baltimore, MD 21201 (United States)

    2012-08-31

    Highlights: Black-Right-Pointing-Pointer Metal nanoparticle for fluorescence cell imaging. Black-Right-Pointing-Pointer Non-invasive emission detection of coenzyme in cell on time-resolved confocal microscope. Black-Right-Pointing-Pointer Near-field interaction of flavin adenine dinucleotide with silver substrate. Black-Right-Pointing-Pointer Isolation of emissions by coenzymes from cellular autofluorescence on fluorescence cell imaging. -- Abstract: Flavin adenine dinucleotide (FAD) is a key metabolite in cellular energy conversion. Flavin can also bind with some enzymes in the metabolic pathway and the binding sites may be changed due to the disease progression. Thus, there is interest on studying its expression level, distribution, and redox state within the cells. FAD is naturally fluorescent, but it has a modest extinction coefficient and quantum yield. Hence the intrinsic emission from FAD is generally too weak to be isolated distinctly from the cellular backgrounds in fluorescence cell imaging. In this article, the metal nanostructures on the glass coverslips were used as substrates to measure FAD in cells. Particulate silver films were fabricated with an optical resonance near the absorption and the emission wavelengths of FAD which can lead to efficient coupling interactions. As a result, the emission intensity and quantum yield by FAD were greatly increased and the lifetime was dramatically shortened resulting in less interference from the longer lived cellular background. This feature may overcome the technical limits that hinder the direct observation of intrinsically fluorescent coenzymes in the cells by fluorescence microscopy. Fluorescence cell imaging on the metallic particle substrates may provide a non-invasive strategy for collecting the information of coenzymes in cells.

  13. Reversal of statin-induced memory dysfunction by co-enzyme Q10: a case report

    Directory of Open Access Journals (Sweden)

    Okeahialam BN

    2015-11-01

    Full Text Available Basil N Okeahialam Cardiology Sub-Unit 1, Department of Medicine, Jos University Teaching Hospital, Jos, Nigeria Abstract: Statins are useful in the armamentarium of the clinician dealing with dyslipidemia, which increases cardiovascular morbi-mortality in hypertensive and diabetic patients among others. Dyslipidemia commonly exists as a comorbidity factor in the development of atherosclerotic cardiovascular disease. Use of statins is however associated with side effects which at times are so disabling as to interfere with activities of daily living. There are various ways of dealing with this, including use of more water-soluble varieties, intermittent dosing, or use of statin alternatives. Of late, use of co-enzyme Q10 has become acceptable for the muscle side effects. Only one report of any benefit on the rarely reported memory side effect was encountered by the author in the search of English medical literature. This is a report of a documented case of a Nigerian woman with history of statin intolerance in this case, memory dysfunction despite persisting dyslipidemia comorbidity. Her memory dysfunction side effect which interfered with activities of daily living and background muscle pain cleared when coenzyme Q10 was administered alongside low dose statin. Her lipid profile normalized and has remained normal. It is being recommended for use when statin side effects (muscle- and memory-related impair quality of life and leave patient at dyslipidemia-induced cardiovascular morbi-mortality. Keywords: statin, memory dysfunction, co-enzyme Q10, improvement

  14. Coenzyme Q10 and alpha-tocopherol protect against amitriptyline toxicity

    International Nuclear Information System (INIS)

    Cordero, Mario D.; Moreno-Fernandez, Ana Maria; Gomez-Skarmeta, Jose Luis; Miguel, Manuel de; Garrido-Maraver, Juan; Oropesa-Avila, Manuel; Rodriguez-Hernandez, Angeles; Navas, Placido; Sanchez-Alcazar, Jose Antonio

    2009-01-01

    Since amitriptyline is a very frequently prescribed antidepressant drug, it is not surprising that amitriptyline toxicity is relatively common. Amitriptyline toxic systemic effects include cardiovascular, autonomous nervous, and central nervous systems. To understand the mechanisms of amitriptyline toxicity we studied the cytotoxic effects of amitriptyline treatment on cultured primary human fibroblasts and zebrafish embryos, and the protective role of coenzyme Q 10 and alpha-tocopherol, two membrane antioxidants. We found that amitriptyline treatment induced oxidative stress and mitochondrial dysfunction in primary human fibroblasts. Mitochondrial dysfunction in amitriptyline treatment was characterized by reduced expression levels of mitochondrial proteins and coenzyme Q 10 , decreased NADH:cytochrome c reductase activity, and a drop in mitochondrial membrane potential. Moreover, and as a consequence of these toxic effects, amitriptyline treatment induced a significant increase in apoptotic cell death activating mitochondrial permeability transition. Coenzyme Q 10 and alpha-tocopherol supplementation attenuated ROS production, lipid peroxidation, mitochondrial dysfunction, and cell death, suggesting that oxidative stress affecting cell membrane components is involved in amitriptyline cytotoxicity. Furthermore, amitriptyline-dependent toxicity and antioxidant protection were also evaluated in zebrafish embryos, a well established vertebrate model to study developmental toxicity. Amitriptyline significantly increased embryonic cell death and apoptosis rate, and both antioxidants provided a significant protection against amitriptyline embryotoxicity

  15. Probing the cob(II)alamin Cond UctorHhypothesis with Glutamate ...

    African Journals Online (AJOL)

    It had been proposed that during reversible coenzyme B12 dependent rearrangements, cob(II)alamin is not merely present as a spectator but also acts as a conductor by stabilizing the methylene radical intermediates. Density functional theory (DFT) calculations suggested a hydrogen bond between C19-H of the corrin ring ...

  16. Thermodynamics of various F420 coenzyme models as sources of electrons, hydride ions, hydrogen atoms and protons in acetonitrile.

    Science.gov (United States)

    Xia, Ke; Shen, Guang-Bin; Zhu, Xiao-Qing

    2015-06-14

    32 F420 coenzyme models with alkylation of the three different N atoms (N1, N3 and N10) in the core structure (XFH(-)) were designed and synthesized and the thermodynamic driving forces (defined in terms of the molar enthalpy changes or the standard redox potentials in this work) of the 32 XFH(-) releasing hydride ions, hydrogen atoms and electrons, the thermodynamic driving forces of the 32 XFH˙ releasing protons and hydrogen atoms and the thermodynamic driving forces of XF(-)˙ releasing electrons in acetonitrile were determined using titration calorimetry and electrochemical methods. The effects of the methyl group at N1, N3 and N10 and a negative charge on N1 and N10 atoms on the six thermodynamic driving forces of the F420 coenzyme models and their related reaction intermediates were examined; the results show that seating arrangements of the methyl group and the negative charge have remarkably different effects on the thermodynamic properties of the F420 coenzyme models and their related reaction intermediates. The effects of the substituents at C7 and C8 on the six thermodynamic driving forces of the F420 coenzyme models and their related reaction intermediates were also examined; the results show that the substituents at C7 and C8 have good Hammett linear free energy relationships with the six thermodynamic parameters. Meanwhile, a reasonable determination of possible reactions between members of the F420 family and NADH family in vivo was given according to a thermodynamic analysis platform constructed using the elementary step thermodynamic parameter of F420 coenzyme model 2FH(-) and NADH model MNAH releasing hydride ions in acetonitrile. The information disclosed in this work can not only fill a gap in the chemical thermodynamics of F420 coenzyme models as a class of very important organic sources of electrons, hydride ions, hydrogen atoms and protons, but also strongly promote the fast development of the chemistry and applications of F420 coenzyme.

  17. Methyl-coenzyme M reductase from methanogenic archaea: isotope effects on label exchange and ethane formation with the homologous substrate ethyl-coenzyme M.

    Science.gov (United States)

    Scheller, Silvan; Goenrich, Meike; Thauer, Rudolf K; Jaun, Bernhard

    2013-10-09

    Ethyl-coenzyme M (CH3CH2-S-CH2CH2-SO3(-), Et-S-CoM) serves as a homologous substrate for the enzyme methyl-coenzyme M reductase (MCR) resulting in the product ethane instead of methane. The catalytic reaction proceeds via an intermediate that already contains all six C-H bonds of the product. Because product release occurs after a second, rate-limiting step, many cycles of intermediate formation and reconversion to substrate occur before a substantial amount of ethane is released. In deuterated buffer, the intermediate becomes labeled, and C-H activation in the back reaction rapidly leads to labeled Et-S-CoM, which enables intermediate formation to be detected. Here, we present a comprehensive analysis of this pre-equilibrium. (2)H- and (13)C-labeled isotopologues of Et-S-CoM were used as the substrates, and the time course of each isotopologue was followed by NMR spectroscopy. A kinetic simulation including kinetic isotope effects allowed determination of the primary and α- and β-secondary isotope effects for intermediate formation and for the C-H/C-D bond activation in the ethane-containing intermediate. The values obtained are in accordance with those found for the native substrate Me-S-CoM (see preceding publication, Scheller, S.; Goenrich, M.; Thauer, R. K.; Jaun, B. J. Am. Chem. Soc. 2013, 135, DOI: 10.1021/ja406485z) and thus imply the same catalytic mechanism for both substrates. The experiment by Floss and co-workers, demonstrating a net inversion of configuration to chiral ethane with CH3CDT-S-CoM as the substrate, is compatible with the observed rapid isotope exchange if the isotope effects measured here are taken into account.

  18. The use of coenzyme Q0 as a template in the development of a molecularly imprinted polymer for the selective recognition of coenzyme Q10.

    Science.gov (United States)

    Contin, Mario; Flor, Sabrina; Martinefski, Manuela; Lucangioli, Silvia; Tripodi, Valeria

    2014-01-07

    In this work, a novel molecularly imprinted polymer (MIP) for use as a solid phase extraction sorbent was developed for the determination of coenzyme Q10 (CoQ10) in liver extract. CoQ10 is an essential cofactor in mitochondrial oxidative phosphorylation and a powerful antioxidant agent found in low concentrations in biological samples. This fact and its high hydrophobicity make the analysis of CoQ10 technically challenging. Accordingly, a MIP was synthesised using coenzyme Q0 as the template, methacrylic acid as the functional monomer, acetonitrile as the porogen, ethylene glycol dimethacrylate as the crosslinker and benzoyl peroxide as the initiator. Various parameters affecting the polymer preparation and extraction efficiency were evaluated. Morphological characterisation of the MIP and its proper comparison with C18 as a sorbent in solid phase extraction were performed. The optimal conditions for the molecularly imprinted solid phase extraction (MISPE) consisted of 400 μL of sample mixed with 30 mg of MIP and 600 μL of water to reach the optimum solution loading. The loading was followed by a washing step consisting of 1 mL of a 1-propanol solution (1-propanol:water, 30:70,v/v) and elution with 1 mL of 1-propanol. After clean-up, the CoQ10 in the samples was analysed by high performance liquid chromatography. The extraction recoveries were higher than 73.7% with good precision (3.6-8.3%). The limits of detection and quantification were 2.4 and 7.5 μg g(-1), respectively, and a linear range between 7.5 and 150 μg g(-1) of tissue was achieved. The new MISPE procedure provided a successful clean-up for the determination of CoQ10 in a complex matrix. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Potential Cardiovascular and Renal Protective Effects of Vitamin D and Coenzyme Q10 in l-NAME-Induced Hypertensive Rats.

    Science.gov (United States)

    Shamardl, Hanan A; El-Ashmony, Sahar M; Kamel, Hala F; Fatani, Sameer H

    2017-08-01

    Hypertension is one of the primary modifiable risk factors for cardiovascular disease. Adequate vitamin D (vit D) levels have been shown to reduce vascular smooth muscle contraction and to increase arterial compliance, which may be beneficial in hypertension. Further, coenzyme Q10 (COQ10) through its action to lower oxidative stress has been reported to have beneficial effects on hypertension and heart failure. This study examined the possible cardiac and renal protective effects of vit D and COQ10 both separately and in combination with an angiotensin II receptor blocker, valsartan (vals) in l-NAME hypertensive rats. Hypertension was induced in rats by l-NAME administration. Following induction of hypertension, the rats were assigned into the following 6 subgroups: an l-NAME alone group and treated groups receiving the following drugs intraperitoneally for 6 weeks; vals, vit D, COQ10 and combination of vals with either vit D or COQ10. A group of normotensive rats were used as negative controls. At the end of the treatment period, blood pressure, serum creatinine, blood urea nitrogen, lipids and serum, cardiac and renal parameters of oxidative stress were measured. Compared to the l-NAME only group, all treatments lowered systolic, diastolic, mean arterial pressure, total cholesterol, low-density lipoprotein cholesterol, and creatinine levels as well as TNF-α and malondialdehyde. Further, the agents increased serum, cardiac and renal total antioxidant capacity. Interestingly, the combination of agents had further effects on all the parameters compared to treatment with each single agent. The study suggests that the additive protective effects of vit D and COQ10 when used alone or concurrent with vals treatment in hypertensive rats may be due to their effects as antioxidants, anticytokines and blood pressure conservers. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  20. Design, optimization and characterization of coenzyme Q10- and D-panthenyl triacetate-loaded liposomes

    Directory of Open Access Journals (Sweden)

    Çelik B

    2017-07-01

    Full Text Available Burak Çelik,1 Ali Asram Sağıroğlu,1 Samet Özdemir2 1Department of Pharmaceutical Technology, Faculty of Pharmacy, Bezmialem Vakif University, 2Department of Pharmaceutical Technology, Faculty of Pharmacy, Yeditepe University, Istanbul, Turkey Abstract: Coenzyme Q10 (CoQ10 is a lipid-soluble molecule found naturally in many eukaryotic cells and is essential for electron transport chain and energy generation in mitochondria. D-Panthenyl triacetate (PTA is an oil-soluble derivative of D-panthenol, which is essential for coenzyme A synthesis in the epithelium. Liposomal formulations that encapsulate both ingredients were prepared and optimized by applying response surface methodology for increased stability and skin penetration. The optimum formulation comprised 4.17 mg CoQ10, 4.22 mg PTA and 13.95 mg cholesterol per 100 mg of soy phosphatidylcholine. The encapsulation efficiency of the optimized formulation for CoQ10 and PTA was found to be 90.89%±3.61% and 87.84%±4.61%, respectively. Narrow size distribution was achieved with an average size of 161.6±3.6 nm, while a spherical and uniform shape was confirmed via scanning electron microscopy and transmission electron microscopy images. Cumulative release of 90.93% for PTA and 24.41% for CoQ10 was achieved after 24 hours of in vitro release study in sink conditions. Physical stability tests indicated that the optimized liposomes were suitable for storage at 4°C for at least 60 days. The results suggest that the optimized liposomal formulation would be a promising delivery system for both ingredients in various topical applications. Keywords: coenzyme Q10, D-panthenyl triacetate, liposomes, response surface methodology, stability

  1. Protection of dichlorvos induced oxidative stress and nigrostriatal neuronal death by chronic Coenzyme Q10 pretreatment

    International Nuclear Information System (INIS)

    Binukumar, BK; Gupta, Nidhi; Bal, Amanjit; Gill, Kiran Dip

    2011-01-01

    Numerous epidemiological studies have shown an association between pesticide exposure and increased risk of developing Parkinson's diseases. Oxidative stress generated as a result of mitochondrial dysfunction has been implicated as an important factor in the etiology of Parkinson's disease. Previously, we reported that chronic dichlorvos exposure causes mitochondrial impairments and nigrostriatal neuronal death in rats. The present study was designed to test whether Coenzyme Q 10 (CoQ 10 ) administration has any neuroprotective effect against dichlorvos mediated nigrostriatal neuronal death, α-synuclein aggregation, and motor dysfunction. Male albino rats were administered dichlorvos by subcutaneous injection at a dose of 2.5 mg/kg body weight over a period of 12 weeks. Results obtained there after showed that dichlorvos exposure leads to enhanced mitochondrial ROS production, α-synuclein aggregation, decreased dopamine and its metabolite levels resulting in nigrostriatal neurodegeneration. Pretreatment by Coenzyme Q 10 (4.5 mg/kg ip for 12 weeks) to dichlorvos treated animals significantly attenuated the extent of nigrostriatal neuronal damage, in terms of decreased ROS production, increased dopamine and its metabolite levels, and restoration of motor dysfunction when compared to dichlorvos treated animals. Thus, the present study shows that Coenzyme Q 10 administration may attenuate dichlorvos induced nigrostriatal neurodegeneration, α-synuclein aggregation and motor dysfunction by virtue of its antioxidant action. - Highlights: → CoQ 10 administration attenuates dichlorvos induced nigrostriatal neurodegenaration. → CoQ 10 pre treatment leads to preservation of TH-IR neurons. → CoQ 10 may decrease oxidative damage and α-synuclin aggregation. → CoQ 10 treatment enhances motor function and protects rats from catalepsy.

  2. [Effect of phlebodium decumanum and coenzyme Q10 on sports performance in professional volleyball players].

    Science.gov (United States)

    García Verazaluce, Juan José; Vargas Corzo, María Del Carmen; Aguilar Cordero, María José; Ocaña Peinado, Francisco; Sarmiento Ramírez, Álvaro; Guisado Barrilao, Rafael

    2014-10-03

    Physical training programmes are based on provoking transitory states of fatigue in order to induce super compensation by the biological systems involved in the activity, in order to improve the athlete's medium-long term performance. The administration of nutritional supplements with antioxidant and immunomodulatory properties, such as Phlebodium decumanum and coenzyme Q10, can be a very advantageous means of achieving recovery from the inflammation and tissue damage caused by the stress of prolonged, intense exercise. An experimental, longitudinal, double- blind experiment was conducted, with three randomised groups obtained from a sample of 30 male volleyball players (aged 22-32 years) at the University of Granada, with a high level of training (17 hours a week during the 6 months preceding the study). The effects were then evaluated of a month-long physical training programme, common to all the study groups, associated with the simultaneous administration of the following nutritional supplements: Phlebodium decumanum (4 capsules of 400 mg/capsule, daily), Experimental Group 1; Phlebodium decumanum (same dose and schedule as Group 1) plus coenzyme Q10 (4 capsules of 30 mg/ capsule, daily), Experimental Group 2; a placebo substance, Control Group. The following dependent blood variables were examined to assess the effects of the intervention on the basal immune and endocrine-metabolic profile: cortisol and interleukin-6, both related to the axis of exercise-induced stress; and lactic acid and ammonium, related essentially to the anaerobic metabolism of energy. All the study groups presented favourable adaptive changes with respect to the endocrine-metabolic and immune profile, as reflected by a significant decrease in the post-test concentrations of cortisol, interleukin 6, lactic acid and ammonium, compared to the values recorded before the physical activity with/without nutritional supplement, per protocol. The groups that achieved the most favourable profile

  3. Inhibition of Coenzyme Qs Accumulation in Engineered Escherichia coli by High Concentration of Farnesyl Diphosphate

    OpenAIRE

    Samoudi, Mojtaba; Omid Yeganeh, Negar; Shahbani Zahiri, Hossein; Shariati, Parvin; Hajhosseini, Reza

    2015-01-01

    Background: Coenzyme Q 10 (CoQ 10 ) is an isoprenoid component used widely in nutraceutical industries. Farnesyl diphosphate synthase (FPPS) is a responsible enzyme for biosynthesis of farnesyl diphosphate (FPP), a key precursor for CoQs production. This research involved investigating the effect of FPPS over-expression on CoQs production in engineered CoQ 10 -producing Escherichia coli (E. coli). Methods: Two CoQ 10 -producing strains, as referred to E. coli Ba and E. coli Br, were transform...

  4. [Coenzyme Q10 (Q-ter) in treatment of functional voice disorders].

    Science.gov (United States)

    Sensini, M; Corvino, A; Passeri, L; Gallone, G O; Landolfo, V; Raimondo, L; Giordano, C

    2011-01-01

    Aim of this study was to evaluate the effectivness of Coenzyme Q-Ter and Vitamin A in functional voice disorders. Twenty two patients were treated with CoQ10-ter and vitamin A twice a day for ten days. A general otolaryngological/foniatric and logopedic examination were performed. Videolaringostroboscopy, GIRBAS, Voice Handicap Index questionnaire and Multi-Dimensional Voice analysis were carried out before and after treatment. In all patients an improvement was observed in almost all parameters considered after treatment. CoQ10-ter and Vitamin A risulted effective in treatment of patients with functional voice disorders (caused by vocal "malmenage" or "surmenage").

  5. Coenzyme Q10 supplementation and exercise-induced oxidative stress in humans

    DEFF Research Database (Denmark)

    Östman, Bengt; Sjödin, Anders Mikael; Michaëlsson, Karl

    2012-01-01

    Objective: The theoretically beneficial effects of coenzyme Q10 (Q10) on exercise-related oxidative stress and physical capacity have not been confirmed to our knowledge by interventional supplementation studies. Our aim was to investigate further whether Q10 supplementation at a dose recommended...... the groups were detected for hypoxanthine or uric acid (serum markers of oxidative stress) or creatine kinase (a marker of skeletal muscle damage). Conclusion: Although in theory Q10 could be beneficial for exercise capacity and in decreasing oxidative stress, the present study could not demonstrate...

  6. Effects of Oral, Vaginal, and Transdermal Hormonal Contraception on Serum Levels of Coenzyme Q10, Vitamin E, and Total Antioxidant Activity

    Directory of Open Access Journals (Sweden)

    Prabhudas R. Palan

    2010-01-01

    coenzyme Q10 levels compared with normal subjects. Serum TAOC levels were significantly lower (P<.05 among the contraceptive user groups. Alterations in coenzyme Q10 and α-tocopherol induced by hormonal contraception and the potential effect(s of exogenous ovarian hormones should be taken into consideration in future antioxidant research.

  7. A randomized controlled trial of coenzyme Q10 for fatigue in the late-onset sequelae of poliomyelitis.

    Science.gov (United States)

    Peel, Margaret M; Cooke, Marie; Lewis-Peel, Helen J; Lea, Rodney A; Moyle, Wendy

    2015-12-01

    To determine if coenzyme Q(10) alleviates fatigue in the late-onset sequelae of poliomyelitis. Parallel-group, randomized, placebo-controlled trial. Coenzyme Q(10) has been shown to boost muscle energy metabolism in post-polio subjects but it does not promote muscle strength, endurance or function in polio survivors with post-poliomyelitis syndrome. However, the collective increased energy metabolism might contribute to a reduction in post-polio fatigue. Polio survivors from the Australian post-polio networks in Queensland and New South Wales who attribute a moderate to high level of fatigue to their diagnosed late-onset sequelae of poliomyelitis. Those with fatigue-associated comorbidities of diabetes, anaemia, hypothyroidism and fibromyalgia were excluded. Participants were assigned (1:1), with stratification of those who use energy-saving mobility aids, to receive 100 mg coenzyme Q(10) or matching placebo daily for 60 days. Participants and investigators were blinded to group allocation. Fatigue was assessed by the Multidimensional Assessment of Fatigue as the primary outcome and the Fatigue Severity Scale as secondary outcome. Of 103 participants, 54 were assigned to receive coenzyme Q(10) and 49 to receive the placebo. The difference in the mean score reductions between the two groups was not statistically significant for either fatigue measure. Oral supplementation with coenzyme Q(10) was safe and well-tolerated. A daily dose of 100 mg coenzyme Q(10) for 60 days does not alleviate the fatigue of the late-onset sequelae of poliomyelitis. The registration number for the clinical trial is ACTRN 12612000552886. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Antiatherogenic, hepatoprotective, and hypolipidemic effects of coenzyme Q10 in alloxan-induced type 1 diabetic rats

    Directory of Open Access Journals (Sweden)

    Hassan Ahmadvand

    2014-07-01

    Full Text Available BACKGROUND: Diabetes mellitus, one of the leading metabolic syndromes, accounts for highest morbidity and mortality worldwide. In this study, we examined possible protective effect of coenzyme Q10 on lipid profile, atherogenic index, and liver enzyme markers in alloxan-induced type 1 diabetic rats. METHODS: A total of 30 male rats were randomly divided into three groups; group 1 as control, group 2 diabetic untreatment, and group 3 treatments with coenzyme Q10 by 15 mg/kg i.p. daily, respectively .Diabetes was induced in the second and third groups by alloxan injection subcutaneously. After 8 weeks, the levels of fasting blood glucose (FBG, triglyceride (TG, total cholesterol (TC, low density lipoprotein (LDL, very low-density lipoprotein (VLDL, high density lipoprotein (HDL, atherogenic index, atherogenic coefficient, cardiac risk ratio, and the activities of alanine aminotransferase (ALT, aspartate aminotransferase (AST, and alkaline phosphatase (ALP of all groups were analyzed. Data were analyzed using non-parametric Mann-Whitney test (using SPSS and P < 0.05 was considered as significant. RESULTS: Coenzyme Q10 inhibited significantly the activities of ALT (11.17%, AST (19.35% and ALP (36.67% and decreased FBG (21.19%, TG (37.24%, TC (17.15%, LDL (30.44%, VLDL (37.24%, atherogenic index (44.24%, atherogenic coefficient (49.69%, and cardiac risk ratio (37.97%, HDL level was significantly (33.38% increased when treated with coenzyme Q10. CONCLUSION: The findings of this study suggest that coenzyme Q10 exert beneficial effects on the lipid profile, atherogenic index, and liver enzymes activity in alloxan-induced type 1 diabetic rats.   Keywords: Diabetes, Lipid Profile, Atherogenic Index, Rats, Liver Enzymes, Coenzyme Q10 

  9. A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit.

    Science.gov (United States)

    Beal, M Flint; Oakes, David; Shoulson, Ira; Henchcliffe, Claire; Galpern, Wendy R; Haas, Richard; Juncos, Jorge L; Nutt, John G; Voss, Tiffini Smith; Ravina, Bernard; Shults, Clifford M; Helles, Karen; Snively, Victoria; Lew, Mark F; Griebner, Brian; Watts, Arthur; Gao, Shan; Pourcher, Emmanuelle; Bond, Louisette; Kompoliti, Katie; Agarwal, Pinky; Sia, Cherissa; Jog, Mandar; Cole, Linda; Sultana, Munira; Kurlan, Roger; Richard, Irene; Deeley, Cheryl; Waters, Cheryl H; Figueroa, Angel; Arkun, Ani; Brodsky, Matthew; Ondo, William G; Hunter, Christine B; Jimenez-Shahed, Joohi; Palao, Alicia; Miyasaki, Janis M; So, Julie; Tetrud, James; Reys, Liza; Smith, Katharine; Singer, Carlos; Blenke, Anita; Russell, David S; Cotto, Candace; Friedman, Joseph H; Lannon, Margaret; Zhang, Lin; Drasby, Edward; Kumar, Rajeev; Subramanian, Thyagarajan; Ford, Donna Stuppy; Grimes, David A; Cote, Diane; Conway, Jennifer; Siderowf, Andrew D; Evatt, Marian Leslie; Sommerfeld, Barbara; Lieberman, Abraham N; Okun, Michael S; Rodriguez, Ramon L; Merritt, Stacy; Swartz, Camille Louise; Martin, W R Wayne; King, Pamela; Stover, Natividad; Guthrie, Stephanie; Watts, Ray L; Ahmed, Anwar; Fernandez, Hubert H; Winters, Adrienna; Mari, Zoltan; Dawson, Ted M; Dunlop, Becky; Feigin, Andrew S; Shannon, Barbara; Nirenberg, Melissa Jill; Ogg, Mattson; Ellias, Samuel A; Thomas, Cathi-Ann; Frei, Karen; Bodis-Wollner, Ivan; Glazman, Sofya; Mayer, Thomas; Hauser, Robert A; Pahwa, Rajesh; Langhammer, April; Ranawaya, Ranjit; Derwent, Lorelei; Sethi, Kapil D; Farrow, Buff; Prakash, Rajan; Litvan, Irene; Robinson, Annette; Sahay, Alok; Gartner, Maureen; Hinson, Vanessa K; Markind, Samuel; Pelikan, Melisa; Perlmutter, Joel S; Hartlein, Johanna; Molho, Eric; Evans, Sharon; Adler, Charles H; Duffy, Amy; Lind, Marlene; Elmer, Lawrence; Davis, Kathy; Spears, Julia; Wilson, Stephanie; Leehey, Maureen A; Hermanowicz, Neal; Niswonger, Shari; Shill, Holly A; Obradov, Sanja; Rajput, Alex; Cowper, Marilyn; Lessig, Stephanie; Song, David; Fontaine, Deborah; Zadikoff, Cindy; Williams, Karen; Blindauer, Karen A; Bergholte, Jo; Propsom, Clara Schindler; Stacy, Mark A; Field, Joanne; Mihaila, Dragos; Chilton, Mark; Uc, Ergun Y; Sieren, Jeri; Simon, David K; Kraics, Lauren; Silver, Althea; Boyd, James T; Hamill, Robert W; Ingvoldstad, Christopher; Young, Jennifer; Thomas, Karen; Kostyk, Sandra K; Wojcieszek, Joanne; Pfeiffer, Ronald F; Panisset, Michel; Beland, Monica; Reich, Stephen G; Cines, Michelle; Zappala, Nancy; Rivest, Jean; Zweig, Richard; Lumina, L Pepper; Hilliard, Colette Lynn; Grill, Stephen; Kellermann, Marye; Tuite, Paul; Rolandelli, Susan; Kang, Un Jung; Young, Joan; Rao, Jayaraman; Cook, Maureen M; Severt, Lawrence; Boyar, Karyn

    2014-05-01

    Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit. To examine whether CoQ10 could slow disease progression in early PD. A phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation. The remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E. Participants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo. The baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants

  10. Probing Reversible Chemistry in Coenzyme B12-Dependent Ethanolamine Ammonia Lyase with Kinetic Isotope Effects

    Science.gov (United States)

    Jones, Alex R; Rentergent, Julius; Scrutton, Nigel S; Hay, Sam

    2015-01-01

    Coenzyme B12-dependent enzymes such as ethanolamine ammonia lyase have remarkable catalytic power and some unique properties that enable detailed analysis of the reaction chemistry and associated dynamics. By selectively deuterating the substrate (ethanolamine) and/or the β-carbon of the 5′-deoxyadenosyl moiety of the intrinsic coenzyme B12, it was possible to experimentally probe both the forward and reverse hydrogen atom transfers between the 5′-deoxyadenosyl radical and substrate during single-turnover stopped-flow measurements. These data are interpreted within the context of a kinetic model where the 5′-deoxyadenosyl radical intermediate may be quasi-stable and rearrangement of the substrate radical is essentially irreversible. Global fitting of these data allows estimation of the intrinsic rate constants associated with CoC homolysis and initial H-abstraction steps. In contrast to previous stopped-flow studies, the apparent kinetic isotope effects are found to be relatively small. PMID:25950663

  11. Free radical scavenging activity of coenzyme Q measured by a chemiluminescent assay

    International Nuclear Information System (INIS)

    Battino, Maurizio; Ferri, Elida; Girotti, Stefano; Lenaz, Giorgio

    1991-01-01

    Involvement of coenzyme Q (CoQ) in anti-oxydant activities, in addition to its major redox role, has frequently been suggested in recent years. In order to elucidate if CoQ could really be engaged in scavenging free radicals produced endogenously in a biological system, an experimental system was developed in which beef heart mitochondria in the presence of a saturating NADH concentration and of rotenone produce free radicals. The presence of oxygen-reactive forms was easily detected by a luminol-dependent chemiluminescence process. The chemi-luminescence assay showed that short-chain CoQ homologues can act as pro-oxidants, enhancing free radical effects, while exogenous coenzyme Q 10 could scavenge free radicals, especially at very low concentration. In this system, exogenous CoQ 10 was more effective than α-tocopherol at the same concentration in scavenging free radicals. The molecular mechanism that leads to this activity is still unclear, but these results are of biochemical importance because they indicate that CoQ may act as an anti=oxidant in situations mimicking physiopathological conditions. This direct chemiluminescent method is promising for studies of biochemical processes which involve active oxygen species. (author). 24 refs.; 4 figs

  12. Characterization of acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) enzyme of human small intestine.

    Science.gov (United States)

    Hiramine, Yasushi; Tanabe, Toshizumi

    2011-06-01

    Acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) enzyme plays a significant role in dietary triacylglycerol (TAG) absorption in the small intestine. However, the characteristics of human intestinal DGAT enzyme have not been examined in detail. The aim of our study was to characterize the human intestinal DGAT enzyme by examining acyl-CoA specificity, temperature dependency, and selectivity for 1,2-diacylglycerol (DAG) or 1,3-DAG. We detected DGAT activity of human intestinal microsome and found that the acyl-CoA specificity and temperature dependency of intestinal DGAT coincided with those of recombinant human DGAT1. To elucidate the selectivity of human intestinal DGAT to 1,2-DAG or 1,3-DAG, we conducted acyl-coenzyme A:monoacylglycerol acyltransferase assays using 1- or 2-monoacylglycerol (MAG) as substrates. When 2-MAG was used as acyl acceptor, both 1,2-DAG and TAG were generated; however, when 1-MAG was used, 1,3-DAG was predominantly observed and little TAG was detected. These findings suggest that human small intestinal DGAT, which is mainly encoded by DGAT1, utilizes 1,2-DAG as the substrate to form TAG. This study will contribute to understand the lipid absorption profile in the small intestine.

  13. Plasma coenzyme Q10 levels in type 2 diabetic patients with retinopathy

    Science.gov (United States)

    Ates, Orhan; Bilen, Habip; Keles, Sadullah; Alp, H. Hakan; Keleş, Mevlüt Sait; Yıldırım, Kenan; Öndaş, Osman; Pınar, L. Can; Civelekler, Mustafa; Baykal, Orhan

    2013-01-01

    AIM To determine the relationship between proliferative diabetic retinopathy (PDRP) and plasma coenzyme Q10(CoQ10) concentration. METHODS Patients with type 2 diabetes and PDRP were determined to be the case group (n=50). The control group was consist of healthy individuals (n=50). Plasma CoQ10 and malondialdehyde (MDA) levels were measured in both groups. RESULTS Ubiquinone-10 (Coenzyme Q10) levels in PDRP and control subjects are 3.81±1.19µmol/L and 1.91±0.62µmol/L, respectively. Plasma MDA levels in PDRP and control subjects were 8.16±2µmol/L and 3.44±2.08µmol/L, respectively. Ratio of Ubiquinol-10/ubiquinone-10 in PDRP and control subjects were 0.26±0.16 and 1.41±0.68, respectively. CONCLUSION The ratio of ubiquinol-10/ubiquinone-10 is found lower in patients with PDRP. High levels of plasma ubiquinol-10/ubiquinone-10 ratio indicate the protective effect on diabetic retinopathy. PMID:24195048

  14. Very long chain acyl-coenzyme A dehydrogenase deficiency with adult onset

    DEFF Research Database (Denmark)

    Smelt, A H; Poorthuis, B J; Onkenhout, W

    1998-01-01

    Very long chain acyl-coenzyme A (acyl-CoA) dehydrogenase (VLCAD) deficiency is a severe disorder of mitochondrial beta-oxidation in infants. We report adult onset of attacks of painful rhabdomyolysis. Gas chromatography identified strongly elevated levels of tetradecenoic acid, 14:1(n-9), tetrade......Very long chain acyl-coenzyme A (acyl-CoA) dehydrogenase (VLCAD) deficiency is a severe disorder of mitochondrial beta-oxidation in infants. We report adult onset of attacks of painful rhabdomyolysis. Gas chromatography identified strongly elevated levels of tetradecenoic acid, 14:1(n-9......), tetradecadienoic acid, 14:2(n-6), and hexadecadienoic acid, 16:2(n-6). Palmitoyl-CoA and behenoyl-CoA dehydrogenase in fibroblasts were deficient. Muscle VLCAD activity was very low. DNA analysis revealed compound heterozygosity for two missense mutations in the VLCAD gene. The relatively mild clinical course may...... be due to residual enzyme activity as a consequence of the two missense mutations. Treatment with L-carnitine and medium chain triglycerides in the diet did not reduce the attacks of rhabdomyolysis....

  15. Plasma coenzyme Q10 levels in type 2 diabetic patients with retinopathy

    Directory of Open Access Journals (Sweden)

    Orhan Ates

    2013-10-01

    Full Text Available AIM: To determine the relationship between proliferative diabetic retinopathy (PDRP and plasma coenzyme Q10(CoQ10 concentration.METHODS: Patients with type 2 diabetes and PDRP were determined to be the case group (n=50. The control group was consist of healthy individuals (n=50. Plasma CoQ10 and malondialdehyde (MDA levels were measured in both groups.RESULTS: Ubiquinone-10 (Coenzyme Q10 levels in PDRP and control subjects are 3.81±1.19µmol/L and 1.91±0.62µmol/L, respectively. Plasma MDA levels in PDRP and control subjects were 8.16±2µmol/L and 3.44±2.08µmol/L, respectively. Ratio of Ubiquinol-10/ubiquinone-10 in PDRP and control subjects were 0.26±0.16 and 1.41±0.68, respectively.CONCLUSION:The ratio of ubiquinol-10/ubiquinone-10 is found lower in patients with PDRP. High levels of plasma ubiquinol-10/ubiquinone-10 ratio indicate the protective effect on diabetic retinopathy.

  16. Substitution of arginine for histidine-47 in the coenzyme binding site of yeast alcohol dehydrogenase I

    International Nuclear Information System (INIS)

    Gould, R.M.; Plapp, B.V.

    1990-01-01

    Molecular modeling of alcohol dehydrogenases suggests that His-47 in the yeast enzyme (His-44 in the protein sequence, corresponding to Arg-47 in the horse liver enzyme) binds the pyrophosphate of the NAD coenzyme. His-47 in the Saccharomyces cerevisiae isoenzyme I was substituted with an arginine by a directed mutation. Steady-state kinetic results at pH 7.3 and 30 degree C of the mutant and wild-type enzymes were consistent with an ordered Bi-Bi mechanism. The substitution decreased dissociation constants by 4-fold for NAD + and 2-fold for NADH while turnover numbers were decreased by 4-fold for ethanol oxidation and 6-fold for acetaldehyde reduction. The magnitudes of these effects are smaller than those found for the same mutation in the human liver β enzyme, suggesting that other amino acid residues in the active site modulate the effects of the substitution. The pH dependencies of dissociation constants and other kinetic constants were similar in the two yeast enzymes. Thus, it appears that His-47 is not solely responsible for a pK value near 7 that controls activity and coenzyme binding rates in the wild-type enzyme. The small substrate deuterium isotope effect above pH 7 and the single exponential phase of NADH production during the transient oxidation of ethanol by the Arg-47 enzyme suggest that the mutation makes an isomerization of the enzyme-NAD + complex limiting for turnover with ethanol

  17. Conserved residues and their role in the structure, function, and stability of acyl-coenzyme A binding protein

    DEFF Research Database (Denmark)

    Kragelund, B B; Poulsen, K; Andersen, K V

    1999-01-01

    In the family of acyl-coenzyme A binding proteins, a subset of 26 sequence sites are identical in all eukaryotes and conserved throughout evolution of the eukaryotic kingdoms. In the context of the bovine protein, the importance of these 26 sequence positions for structure, function, stability...

  18. Beneficial Effects of Coenzyme Q10 in Reduction of Testicular Tissue Alteration Following Induction of Diabetes in Adult Rats

    Directory of Open Access Journals (Sweden)

    Kianifard Davoud

    2015-03-01

    Full Text Available Background and Aims: Various types of infertility are associated with uncontrolled hyperglycemia and diabetes. Development of oxidative stress is one the most important factors in the alteration of spermatogenesis in diabetic conditions. Consequently, the reduction of oxidative stress with antioxidant compounds can be effective in the reduction of tissue alterations. The aim of this study was to evaluate the efficacy of coenzyme Q10 in improvement of spermatogenesis in adult diabetic rats. Material and Methods: 32 adult rats were divided into four groups of control and treatment. Coenzyme Q10 (10 mg/kg body weight - b.w. was administrated to one control and one diabetic (intraperitoneal injection of 45 mg/kg b.w. of Streptozotocin groups. Blood concentrations of FSH, LH and Testosterone were measured. Histology of testicular tissue and sperm analysis were considered for evaluation of spermatogenesis. Results: Administration of Coenzyme Q10 led to increase of pituitary gonadotropins levels in diabetic rats. Testosterone levels were not changed significantly. Testicular morphology, spermatogenic indices and sperm analysis were improved in treated diabetic rats. Conclusions: The results of this study suggest that the use of Coenzyme Q10 has positive effects in reduction of spermatogenic alterations following induction of experimental diabetes in rats.

  19. Lithium carbonate and coenzyme Q10 reduce cell death in a cell model of Machado-Joseph disease

    Directory of Open Access Journals (Sweden)

    C.M. Lopes-Ramos

    Full Text Available Machado-Joseph disease (MJD or spinocerebellar ataxia type 3 (SCA3 is an autosomal dominant neurodegenerative disorder caused by expansion of the polyglutamine domain of the ataxin-3 (ATX3 protein. MJD/SCA3 is the most frequent autosomal dominant ataxia in many countries. The mechanism underlying MJD/SCA3 is thought to be mainly related to protein misfolding and aggregation leading to neuronal dysfunction followed by cell death. Currently, there are no effective treatments for patients with MJD/SCA3. Here, we report on the potential use of lithium carbonate and coenzyme Q10 to reduce cell death caused by the expanded ATX3 in cell culture. Cell viability and apoptosis were evaluated by MTT assay and by flow cytometry after staining with annexin V-FITC/propidium iodide. Treatment with lithium carbonate and coenzyme Q10 led to a significant increase in viability of cells expressing expanded ATX3 (Q84. In addition, we found that the increase in cell viability resulted from a significant reduction in the proportion of apoptotic cells. Furthermore, there was a significant change in the expanded ATX3 monomer/aggregate ratio after lithium carbonate and coenzyme Q10 treatment, with an increase in the monomer fraction and decrease in aggregates. The safety and tolerance of both drugs are well established; thus, our results indicate that lithium carbonate and coenzyme Q10 are good candidates for further in vivo therapeutic trials.

  20. Rosuvastatin lowers coenzyme Q10 levels, but not mitochondrial adenosine triphosphate synthesis, in children with familial hypercholesterolemia

    NARCIS (Netherlands)

    Avis, Hans J.; Hargreaves, Ian P.; Ruiter, Jos P. N.; Land, John M.; Wanders, Ronald J.; Wijburg, Frits A.

    2011-01-01

    To investigate whether statin therapy affects coenzyme Q10 (CoQ10) status in children with heterozygous familial hypercholesterolemia (FH). Samples were obtained at baseline (treatment naïve) and after dose titration with rosuvastatin, aiming for a low-density lipoprotein cholesterol level of 110

  1. Coenzyme Q10 and pro-inflammatory markers in children with Down syndrome: clinical and biochemical aspects

    Directory of Open Access Journals (Sweden)

    Moushira E. Zaki

    2017-01-01

    Conclusion: Interleukin 6 and tumor necrosis factor α levels in young children with Down syndrome may be used as biomarkers reflecting the neurodegenerative process in them. Coenzyme Q10 might have a role as a good supplement in young children with Down syndrome to ameliorate the neurological symptoms.

  2. Rotational barriers of 1,3-substitute pyridines and benzenes as models for the NAD+/NADH coenzyme

    NARCIS (Netherlands)

    Vanhommerig, S.A.M.; Meier, R.J.; Sluyterman, L.A.A.E.; Meijer, E.M.

    1994-01-01

    The NAD+/NADH coenzyme is involved in many enzyme-catalysed oxidation-reduction reactions. In order to obtain better insight in the catalytic mechanism of NAD+/NADH dependent dehydrogenases, conformational studies of 1,3-substituted pyridines and benzenes were carried out, using ab initio,

  3. Coenzyme Q10 does not prevent oral dyskinesias induced by long-term haloperidol treatment of rats

    DEFF Research Database (Denmark)

    OA, Andreassen; Weber, Christine; HA, Jorgensen

    1999-01-01

    dyskinesias in rats, a putative analogue to human TD, could be prevented by the antioxidant coenzyme Q10 (CoQ10). Rats received 16 weeks of treatment with haloperidol decanoate (HAL) IM alone or together with orally administered CoQ10, and the behavior was recorded during and after treatment. HAL...

  4. Coenzyme Q10 supplementation decreases statin-related mild-to-moderate muscle symptoms: a randomized clinical study.

    Science.gov (United States)

    Skarlovnik, Ajda; Janić, Miodrag; Lunder, Mojca; Turk, Martina; Šabovič, Mišo

    2014-11-06

    Statin use is frequently associated with muscle-related symptoms. Coenzyme Q10 supplementation has yielded conflicting results in decreasing statin myopathy. Herein, we tested whether coenzyme Q10 supplementation could decrease statin-associated muscular pain in a specific group of patients with mild-to-moderate muscle symptoms. Fifty patients treated with statins and reporting muscle pain were recruited. The Q10 group (n=25) received coenzyme Q10 supplementation over a period of 30 days (50 mg twice daily), and the control group (n=25) received placebo. The Brief Pain Inventory (BPI) questionnaire was used and blood testing was performed at inclusion in the study and after 30 days of supplementation. The intensity of muscle pain, measured as the Pain Severity Score (PSS), in the Q10 group was reduced from 3.9±0.4 to 2.9±0.4 (PPain Interference Score (PIS) after Q10 supplementation was reduced from 4.0±0.4 to 2.6±0.4 (Pstatin-related muscle symptoms in 75% of patients. The relative values of PSS and PIS significantly decreased (-33.1% and -40.3%, respectively) in the Q10 group compared to placebo group (both Pmuscle enzymes or cholesterol values were found. The present results show that coenzyme Q10 supplementation (50 mg twice daily) effectively reduced statin-related mild-to-moderate muscular symptoms, causing lower interference of statin-related muscular symptoms with daily activities.

  5. Clinical presentation and outcome in a series of 32 patients with 2-methylacetoacetyl-coenzyme A thiolase (MAT) deficiency

    NARCIS (Netherlands)

    Grünert, Sarah Catharina; Schmitt, Robert Niklas; Schlatter, Sonja Marina; Gemperle-Britschgi, Corinne; Balci, Mehmet Cihan; Berg, Volker; Çoker, Mahmut; Das, Anibh M; Demirkol, Mübeccel; Derks, Terry G J; Gökçay, Gülden; Uçar, Sema Kalkan; Konstantopoulou, Vassiliki; Christoph Korenke, G.; Lotz-Havla, Amelie Sophia; Schlune, Andrea; Staufner, Christian; Tran, Christel; Visser, Gepke; Schwab, Karl Otfried; Fukao, Toshiyuki; Sass, Jörn Oliver

    2-methylacetoacetyl-coenzyme A thiolase (MAT) deficiency, also known as beta-ketothiolase deficiency, is an inborn error of ketone body utilization and isoleucine catabolism. It is caused by mutations in the ACAT1 gene and may present with metabolic ketoacidosis. In order to obtain a more

  6. Protective Effect of Coenzyme Q10 on Methamphetamine-Induced Apoptosis in Adult Male Rats

    Directory of Open Access Journals (Sweden)

    Fatemeh Gholipour

    2017-06-01

    Full Text Available Background: The negative consequence of methamphetamine abuse is due to neuropathologic changes in the brain, which reduces dopaminergic neurons and result in damage to different brain areas. Neurotoxicity induced by methamphetamine increases the oxidative stress and associated with neuronal apoptosis. The role of the antioxidant coenzyme Q10 probably produces its neuroprotective effects. Therefore, the purpose of the present study was to examine the protective effect of coenzyme Q10 on methamphetamine-induced apoptosis in adult male rats.Materials and Methods: Fifty Wistar eight-week adult rats randomly divided into 5 groups: Healthy control, methamphetamine injection (Meth, methamphetamine injection and CoQ10 5mg/kg treatment (Meth+Post CoQ10 5mg/kg, methamphetamine injection and CoQ10 10mg/kg treatment (Meth+Post CoQ10 10mg/kg, methamphetamine injection and CoQ10 20mg/kg treatment (Meth+Post CoQ10 20mg/kg. Methamphetamine with a purity of 96% with a dosage of 20 mg/kg was injected Intraperitoneal. Coenzyme Q10 for three treatment groups was injected intraperitoneally for 14 days in a dosage of 5, 10 and 20 mg/kg/day. The protein expressions of Baxand Bcl2 were evaluated by western blotting technique.Results: Bax protein expression was significantly lower in Meth+Post CoQ10 5mg/kg (p=0.010 and so Meth+Post CoQ10 10mg/kg (p=0.004 comparing to Meth group. In addition, Bcl2 protein expression was significantly higher in Meth+Post CoQ10 5mg/kg comparing to Meth group (p=0.018. However, there were no significant differences between control and CoQ10 treatment groups. Bax/Bcl2 ratio was significantly lower in Meth+Post CoQ10 5mg/kg (p=0.005, Meth+Post CoQ10 10mg/kg (p=0.008 and Meth+Post CoQ10 20mg/kg (p=0.044 comparing to Meth group.Conclusion: We suggest that CoQ10 reduces the methamphetamine-induced apoptosis in the striatum of the rats through the reduction of apoptotic factors and increase of anti-apoptotic pathways.

  7. Synthesis, solution and crystal structure of the coenzyme B(12) analogue Co(β)-2'-fluoro-2',5'-dideoxyadenosylcobalamin.

    Science.gov (United States)

    Hunger, Miriam; Wurst, Klaus; Kräutler, Bernhard

    2015-07-01

    Crystal structure analyses have helped to decipher the mode of binding of coenzyme B12 (AdoCbl) in the active site of AdoCbl-dependent enzymes. However, the question of how such enzymes perform their radical reactions is still incompletely answered. A pioneering study by Gruber and Kratky of AdoCbl-dependent glutamate mutase (GLM) laid out a path for the movement of the catalytically active 5'-deoxyadenosyl radical, in which H-bonds between the protein and the 2'- and 3'-OH groups of the protein bound AdoCbl would play a decisive role. Studies with correspondingly modified coenzyme B12-analogues are of interest to gain insights into cofactor binding and enzyme mechanism. Here we report the preparation of Coβ-2'-fluoro-2',5'-dideoxyadenosylcobalamin (2'FAdoCbl), which lacks the 2'-OH group critical for the interaction in enzymes. 2'FAdoCbl was prepared by alkylation of cob(I)alamin, obtained from the electrochemical reduction of aquocobalamin. Spectroscopic data and a single crystal X-ray analysis of 2'FAdoCbl established its structure, which was very similar to that one of coenzyme B12. 2'FAdoCbl is a (19)F NMR active mimic of coenzyme B12 that may help to gain insights into binding interactions of coenzyme B12 with AdoCbl-dependent enzymes, proteins of B12 transport and of AdoCbl-biosynthesis, as well as with B12-riboswitches. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Coenzyme Q10 and pro-inflammatory markers in children with Down syndrome: clinical and biochemical aspects.

    Science.gov (United States)

    Zaki, Moushira E; El-Bassyouni, Hala T; Tosson, Angie M S; Youness, Eman; Hussein, Jihan

    Evidence of oxidative stress was reported in individuals with Down syndrome. There is a growing interest in the contribution of the immune system in Down syndrome. The aim of this study is to evaluate the coenzyme Q10 and selected pro-inflammatory markers such as interleukin 6 and tumor necrosis factor α in children with Down syndrome. Eighty-six children (5-8 years of age) were enrolled in this case-control study from two public institutions. At the time of sampling, the patients and controls suffered from no acute or chronic illnesses and received no therapies or supplements. The levels of interleukin 6, tumor necrosis factor α, coenzyme Q10, fasting blood glucose, and intelligence quotient were measured. Forty-three young Down syndrome children and forty-three controls were included over a period of eight months (January-August 2014). Compared with the control group, the Down syndrome patients showed significant increase in interleukin 6 and tumor necrosis factor α (p=0.002), while coenzyme Q10 was significantly decreased (p=0.002). Also, body mass index and fasting blood glucose were significantly increased in patients. There was a significantly positive correlation between coenzyme Q10 and intelligence quotient levels, as well as between interleukin 6 and tumor necrosis factor α. Interleukin 6 and tumor necrosis factor α levels in young children with Down syndrome may be used as biomarkers reflecting the neurodegenerative process in them. Coenzyme Q10 might have a role as a good supplement in young children with Down syndrome to ameliorate the neurological symptoms. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  9. Coenzyme Q10 and pro-inflammatory markers in children with Down syndrome: clinical and biochemical aspects

    Directory of Open Access Journals (Sweden)

    Moushira E. Zaki

    Full Text Available Abstract: Objective: Evidence of oxidative stress was reported in individuals with Down syndrome. There is a growing interest in the contribution of the immune system in Down syndrome. The aim of this study is to evaluate the coenzyme Q10 and selected pro-inflammatory markers such as interleukin 6 and tumor necrosis factor α in children with Down syndrome. Methods: Eighty-six children (5-8 years of age were enrolled in this case-control study from two public institutions. At the time of sampling, the patients and controls suffered from no acute or chronic illnesses and received no therapies or supplements. The levels of interleukin 6, tumor necrosis factor α, coenzyme Q10, fasting blood glucose, and intelligence quotient were measured. Results: Forty-three young Down syndrome children and forty-three controls were included over a period of eight months (January-August 2014. Compared with the control group, the Down syndrome patients showed significant increase in interleukin 6 and tumor necrosis factor α (p = 0.002, while coenzyme Q10 was significantly decreased (p = 0.002. Also, body mass index and fasting blood glucose were significantly increased in patients. There was a significantly positive correlation between coenzyme Q10 and intelligence quotient levels, as well as between interleukin 6 and tumor necrosis factor α. Conclusion: Interleukin 6 and tumor necrosis factor α levels in young children with Down syndrome may be used as biomarkers reflecting the neurodegenerative process in them. Coenzyme Q10 might have a role as a good supplement in young children with Down syndrome to ameliorate the neurological symptoms.

  10. How Chain Length and Charge Affect Surfactant Denaturation of Acyl Coenzyme A Binding Protein (ACBP)

    DEFF Research Database (Denmark)

    Andersen, Kell Kleiner; Otzen, Daniel

    2009-01-01

    maltoside (DDM). The aim has been to determine how surfactant chain length and micellar charge affect the denaturation mechanism. ACBP denatures in two steps irrespective of surfactant chain length, but with increasing chain length, the potency of the denaturant rises more rapidly than the critical micelle......Using intrinsic tryptophan fluorescence, equilibria and kinetics of unfolding of acyl coenzyme A binding protein (ACBP) have been investigated in sodium alkyl sulfate surfactants of different chain length (8-16 carbon atoms) and with different proportions of the nonionic surfactant dodecyl...... constants increases linearly with denaturant concentration below the cmc but declines at higher concentrations. Both shortening chain length and decreasing micellar charge reduce the overall kinetics of unfolding and makes the dependence of unfolding rate constants on surfactant concentration more complex...

  11. Application of coenzyme Q10 for accelerating soft tissue wound healing after tooth extraction in rats.

    Science.gov (United States)

    Yoneda, Toshiki; Tomofuji, Takaaki; Kawabata, Yuya; Ekuni, Daisuke; Azuma, Tetsuji; Kataoka, Kota; Kunitomo, Muneyoshi; Morita, Manabu

    2014-12-10

    Accelerating wound healing after tooth extraction is beneficial in dental treatment. Application of antioxidants, such as reduced coenzyme Q10 (rCoQ10), may promote wound healing after tooth extraction. In this study, we examined the effects of topical application of rCoQ10 on wound healing after tooth extraction in rats. After maxillary first molars were extracted, male Fischer 344 rats (8 weeks old) (n = 27) received topical application of ointment containing 5% rCoQ10 (experimental group) or control ointment (control group) to the sockets for 3 or 8 days (n = 6-7/group). At 3 days after extraction, the experimental group showed higher collagen density and lower numbers of polymorphonuclear leukocytes in the upper part of socket, as compared to the control group (p healing in the soft tissue of the alveolar socket, but that rCoQ10 has a limited effect on bone remodeling in rats.

  12. Effects of aeration on formation and localization of the acetyl coenzyme A synthetases of Saccharomyces cerevisiae

    Science.gov (United States)

    Klein, H. P.; Jahnke, L.

    1979-01-01

    Previous studies on the yeast Saccharomyces cerevisiae have shown that two different forms of the enzyme acetyl coenzyme A synthetase (ACS) are present, depending on the conditions under which the cells are grown. The paper evaluates the usefulness of a method designed to assay both synthetases simultaneously in yeast homogenates. The data presented confirm the possibility of simultaneous detection and estimation of the amount of both ACSs of S. cerevisiae in crude homogenates of this strain, making possible the study of physiological factors involved in the formation of these isoenzymes. One important factor for specifying which of the two enzymes is found in these yeast cells is the presence or absence of oxygen in their environment. Aeration not only affects the ratio of the two ACSs but also appears to affect the cellular distribution of these enzymes. Most of the data presented suggest the possibility that the nonaerobic ACS may serve as a precursor to the aerobic form.

  13. Factors affecting the palmitoyl-coenzyme A desaturase of Saccharomyces cerevisiae

    Science.gov (United States)

    Klein, H. P.; Volkmann, C. M.

    1975-01-01

    The activity and stability of the palmitoyl-coenzyme A (CoA) desaturase complex of Saccharomyces cerevisiae was influenced by several factors. Cells, grown nonaerobically and then incubated with glucose, either in air or under N2, showed a marked increase in desaturase activity. Cycloheximide, added during such incubations, prevented the increase in activity, suggesting de novo synthesis. The stability of the desaturase from cells grown nonaerobically was affected by subsequent treatment of the cells; enzyme from freshly harvested cells, or from cells that were then shaken under nitrogen, readily lost activity upon washing or during density gradient analysis, whereas aerated cells, in the presence or absence of glucose, yielded stable enzyme preparations. The loss of activity in nonaerobic preparations could be reversed by adding soluble supernatant from these homogenates and could be prevented by growing the cells in the presence of palmitoleic acid and ergosterol, but not with several other lipids tested.

  14. Fulminant lipid storage myopathy due to multiple acyl-coenzyme a dehydrogenase deficiency.

    Science.gov (United States)

    Whitaker, Charles H; Felice, Kevin J; Silvers, David; Wu, Qian

    2015-08-01

    The lipid storage myopathies, primary carnitine deficiency, neutral lipid storage disease, and multiple acyl coenzyme A dehydrogenase deficiency (MADD), are progressive disorders that cause permanent weakness. These disorders of fatty acid metabolism and intracellular triglyceride degradation cause marked fat deposition and damage to muscle cells. We describe a rapidly progressive myopathy in a previously healthy 33-year-old woman. Over 4 months, she developed a proximal and axial myopathy associated with diffuse myalgia and dysphagia, ultimately leading to respiratory failure and death. Muscle biopsy showed massive accumulation of lipid. Plasma acylcarnitine and urine organic acid analysis was consistent with MADD. This was confirmed by molecular genetic testing, which revealed 2 pathogenic mutations in the ETFDH gene. This report illustrates a late-onset case of MADD and reviews the differential diagnosis and evaluation of patients with proximal myopathy and excessive accumulation of lipid on muscle biopsy. © 2014 Wiley Periodicals, Inc.

  15. Acyl coenzyme A thioesterase 7 regulates neuronal fatty acid metabolism to prevent neurotoxicity.

    Science.gov (United States)

    Ellis, Jessica M; Wong, G William; Wolfgang, Michael J

    2013-05-01

    Numerous neurological diseases are associated with dysregulated lipid metabolism; however, the basic metabolic control of fatty acid metabolism in neurons remains enigmatic. Here we have shown that neurons have abundant expression and activity of the long-chain cytoplasmic acyl coenzyme A (acyl-CoA) thioesterase 7 (ACOT7) to regulate lipid retention and metabolism. Unbiased and targeted metabolomic analysis of fasted mice with a conditional knockout of ACOT7 in the nervous system, Acot7(N-/-), revealed increased fatty acid flux into multiple long-chain acyl-CoA-dependent pathways. The alterations in brain fatty acid metabolism were concomitant with a loss of lean mass, hypermetabolism, hepatic steatosis, dyslipidemia, and behavioral hyperexcitability in Acot7(N-/-) mice. These failures in adaptive energy metabolism are common in neurodegenerative diseases. In agreement, Acot7(N-/-) mice exhibit neurological dysfunction and neurodegeneration. These data show that ACOT7 counterregulates fatty acid metabolism in neurons and protects against neurotoxicity.

  16. Coenzyme Q10 Supplementation Modulates NFκB and Nrf2 Pathways in Exercise Training

    Directory of Open Access Journals (Sweden)

    Ragip Pala, Cemal Orhan, Mehmet Tuzcu, Nurhan Sahin, Shakir Ali, Vedat Cinar, Mustafa Atalay, Kazim Sahin

    2016-03-01

    Full Text Available This study reports the effects of Q10, coenzyme Q10 or ubiquinone, a component of the electron transport chain in mitochondria, on nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB, inhibitors of kappa B (IκB, nuclear factor (erythroid-derived 2-like 2 (Nrf2 and hemeoxygenase 1 (HO-1 in rats after chronic exercise training for 6 weeks. 8-week old male Wistar rats were assigned randomly to one of four treatments planned in a 2 x 2 factorial arrangement of two condition (sedentary vs. exercise training, and two coenzyme Q10 levels (0 and 300 mg/kg per day for 6 weeks. The expression levels of the target proteins were determined in the heart, liver and muscle, and biochemical parameters including creatinine, urea, glucose and lipid profile were investigated in plasma. When compared with sedentary group, significant decreases in heart, liver and muscle NFκB levels by 45%, 26% and 44% were observed in Q10 supplemented rats after exercise training, respectively, while the inhibitory protein IκB increased by 179%, 111% and 127% in heart, liver and muscle tissues. Q10 supplementation caused an increase in Nrf2 (167%, 165% and 90% and HO-1 (107%, 156% and 114% after exercise training in heart, liver and muscle tissues (p < 0.05. No significant change was observed in any of the parameters associated with protein, carbohydrate and lipid metabolism, except that exercise caused a decrease in plasma triglyceride, which was further decreased by Q10. In conclusion, these results suggest that Q10 modulates the expression of NFκB, IκB, Nrf2 and HO-1 in exercise training, indicating an anti-inflammatory effect of Q10 and emphasizes its role in antioxidant defense.

  17. Coenzyme Q10 plus Multivitamin Treatment Prevents Cisplatin Ototoxicity in Rats.

    Directory of Open Access Journals (Sweden)

    Laura Astolfi

    Full Text Available Cisplatin (Cpt is known to induce a high level of oxidative stress, resulting in an increase of reactive oxygen species damaging the inner ear and causing hearing loss at high frequencies. Studies on animal models show that antioxidants may lower Cpt-induced ototoxicity. The aim of this study is to evaluate the ototoxic effects of two different protocols of Cpt administration in a Sprague-Dawley rat model, and to test in the same model the synergic protective effects of a solution of coenzyme Q10 terclatrate and Acuval 400®, a multivitamin supplement containing antioxidant agents and minerals (Acu-Qter. The Cpt was administered intraperitoneally in a single dose (14 mg/kg or in three daily doses (4.6 mg/kg/day to rats orally treated or untreated with Acu-Qter for 5 days. The auditory function was assessed by measuring auditory brainstem responses from 2 to 32 kHz at day 0 and 5 days after treatment. Similar hearing threshold and body weight alterations were observed in both Cpt administration protocols, but mortality reduced to zero when Cpt was administered in three daily doses. The Acu-Qter treatment was able to prevent and completely neutralize ototoxicity in rats treated with three daily Cpt doses, supporting the synergic protective effects of coenzyme Q terclatrate and Acuval 400® against Cpt-induced oxidative stress. The administration protocol involving three Cpt doses is more similar to common human chemotherapy protocols, therefore it appears more useful for long-term preclinical studies on ototoxicity prevention.

  18. Sensitive non-radioactive determination of aminotransferase stereospecificity for C-4' hydrogen transfer on the coenzyme.

    Science.gov (United States)

    Jomrit, Juntratip; Summpunn, Pijug; Meevootisom, Vithaya; Wiyakrutta, Suthep

    2011-02-25

    A sensitive non-radioactive method for determination of the stereospecificity of the C-4' hydrogen transfer on the coenzymes (pyridoxal phosphate, PLP; and pyridoxamine phosphate, PMP) of aminotransferases has been developed. Aminotransferase of unknown stereospecificity in its PLP form was incubated in (2)H(2)O with a substrate amino acid resulted in PMP labeled with deuterium at C-4' in the pro-S or pro-R configuration according to the stereospecificity of the aminotransferase tested. The [4'-(2)H]PMP was isolated from the enzyme protein and divided into two portions. The first portion was incubated in aqueous buffer with apo-aspartate aminotransferase (a reference si-face specific enzyme), and the other was incubated with apo-branched-chain amino acid aminotransferase (a reference re-face specific enzyme) in the presence of a substrate 2-oxo acid. The (2)H at C-4' is retained with the PLP if the aminotransferase in question transfers C-4' hydrogen on the opposite face of the coenzyme compared with the reference aminotransferase, but the (2)H is removed if the test and reference aminotransferases catalyze hydrogen transfer on the same face. PLP formed in the final reactions was analyzed by LC-MS/MS for the presence or absence of (2)H. The method was highly sensitive that for the aminotransferase with ca. 50 kDa subunit molecular weight, only 2mg of the enzyme was sufficient for the whole test. With this method, the use of radioactive substances could be avoided without compromising the sensitivity of the assay. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. TD-DFT Insight into Photodissociation of Co-C Bond in Coenzyme B12

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    Pawel Michal Kozlowski

    2014-02-01

    Full Text Available Coenzyme B12 (AdoCbl is one of the most biologically active forms of vitamin B12, and continues to be a topic of active research interest. The mechanism of Co-C bond cleavage in AdoCbl, and the corresponding enzymatic reactions are however, not well understood at the molecular level. In this work, time-dependent density functional theory (TD-DFT has been applied to investigate the photodissociation of coenzyme B12. To reduce computational cost, while retaining the major spectroscopic features of AdoCbl, a truncated model based on ribosylcobalamin (RibCbl was used to simulate Co-C photodissociation. Equilibrium geometries of RibCbl were obtained by optimization at the DFT/BP86/TZVP level of theory, and low-lying excited states were calculated by TD-DFT using the same functional and basis set. The calculated singlet states, and absorption spectra were simulated in both the gas phase, and water, using the polarizable continuum model (PCM. Both spectra were in reasonable agreement with experimental data, and potential energy curves based on vertical excitations were plotted to explore the nature of Co-C bond dissociation. It was found that a repulsive 3(σCo-C → σ*Co-C triplet state became dissociative at large Co-C bond distance, similar to a previous observation for methylcobalamin (MeCbl. Furthermore, potential energy surfaces (PESs obtained as a function of both Co-CRib and Co-NIm distances, identify the S1 state as a key intermediate generated during photoexcitation of RibCbl, attributed to a mixture of a MLCT (metal-to-ligand charge transfer and a σ bonding-ligand charge transfer (SBLCT states.

  20. Potential role of coenzyme Q10 in health and disease conditions

    Directory of Open Access Journals (Sweden)

    Rodick TC

    2018-02-01

    Full Text Available Taylor C Rodick,1 Donna R Seibels,2 Jeganathan Ramesh Babu,1 Kevin W Huggins,1 Guang Ren,3 Suresh T Mathews2 1Department of Nutrition, Dietetics, & Hospitality Management, Auburn University, Auburn, 2Department of Nutrition and Dietetics, Samford University, 3Medicine-Endocrinology, Diabetes & Metabolism, University of Alabama at Birmingham, Birmingham, AL, USA Abstract: Coenzyme Q10 (CoQ10, an endogenously produced compound, is found in all human cells. Within the mitochondria, it plays a substantial role in energy production by acting as a mobile electron carrier in the electron transport chain. Outside the mitochondria, it acts as an excellent antioxidant by sequestering free radicals and working synergistically with other antioxidants, including vitamin E. Dietary contribution is limited, making endogenous production the primary source for optimal function. Now widely available as an over-the-counter supplement, CoQ10 has gained attention for its possible therapeutic use in minimizing the outcomes of certain metabolic diseases, notably cardiovascular disease, diabetes, neurodegenerative disease, and cancer. Research has shown positive results in subjects supplemented with CoQ10, especially in relation to upregulating antioxidant capability. Emerging research suggests beneficial effects of CoQ10 supplementation in individuals on statin medications. CoQ10 supplementation in individuals participating in strenuous exercise seems to exert some beneficial effects, although the data are conflicting with other types of physical activity. This broad review of current CoQ10 literature, while outlining its physiological/functional significance in health and disease conditions, also offers a dietitian’s perspective on its potential use as a supplement in the promotion of health and management of disease conditions. Keywords: coenzyme Q, antioxidant, oxidative stress, dietary supplement, statin

  1. Altered bacterial metabolism, not coenzyme Q content, is responsible for the lifespan extension in Caenorhabditis elegans fed an Escherichia coli diet lacking coenzyme Q.

    Science.gov (United States)

    Saiki, Ryoichi; Lunceford, Adam L; Bixler, Tarra; Dang, Peter; Lee, Wendy; Furukawa, Satoru; Larsen, Pamela L; Clarke, Catherine F

    2008-06-01

    Coenzyme Q(n) is a fully substituted benzoquinone containing a polyisoprene tail of distinct numbers (n) of isoprene groups. Caenorhabditis elegans fed Escherichia coli devoid of Q(8) have a significant lifespan extension when compared to C. elegans fed a standard 'Q-replete'E. coli diet. Here we examine possible mechanisms for the lifespan extension caused by the Q-less E. coli diet. A bioassay for Q uptake shows that a water-soluble formulation of Q(10) is effectively taken up by both clk-1 mutant and wild-type nematodes, but does not reverse lifespan extension mediated by the Q-less E. coli diet, indicating that lifespan extension is not due to the absence of dietary Q per se. The enhanced longevity mediated by the Q-less E. coli diet cannot be attributed to dietary restriction, different Qn isoforms, reduced pathogenesis or slowed growth of the Q-less E. coli, and in fact requires E. coli viability. Q-less E. coli have defects in respiratory metabolism. C. elegans fed Q-replete E. coli mutants with similarly impaired respiratory metabolism due to defects in complex V also show a pronounced lifespan extension, although not as dramatic as those fed the respiratory deficient Q-less E. coli diet. The data suggest that feeding respiratory incompetent E. coli, whether Q-less or Q-replete, produces a robust life extension in wild-type C. elegans. We believe that the fermentation-based metabolism of the E. coli diet is an important parameter of C. elegans longevity.

  2. Expressions of the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase genes are stimulated by recombinant platelet-derived growth factor isomers

    International Nuclear Information System (INIS)

    Roth, M.; Emmons, L.R.; Perruchoud, A.; Block, L.H.

    1991-01-01

    The plausible role that platelet-derived growth factor (PDGF) has in the localized pathophysiological changes that occur in the arterial wall during development of atherosclerotic lesions led the authors to investigate the influence of recombinant (r)PDGF isomers -AA, -AB, and -BB on the expression of low density lipoprotein receptor (LDL-R) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG0CoA) reductase [(S)-mevalonate:NAD + oxidoreductase (CoA-acylating), EC 1.1.1.88] genes. In addition, they clarified the role of protein kinase C (PKC) in expression of the two genes in human skin fibroblasts and vascular smooth muscle cells. The various rPDGF isoforms are distinct in their ability to activate transcription of both genes: (i) both rPDGF-AA and -BB stimulate transcription of the LDL-R gene; in contrast, rPDGF-BB but not -AA, activates transcription of the HMG-CoA reductase gene; (ii) all recombinant isoforms of PDGF activate transcription of the c-fos gene; (iii) while rPDGF-dependent transcription of the lDL-R gene occurs independently of PKC, transcription of the HMG-CoA reductase gene appears to involve the action of that enzyme

  3. cobalt (ii), nickel (ii)

    African Journals Online (AJOL)

    DR. AMINU

    Department of Chemistry Bayero University, P. M. B. 3011, Kano, Nigeria. E-mail: hnuhu2000@yahoo.com. ABSTRACT. The manganese (II), cobalt (II), nickel (II) and .... water and common organic solvents, but are readily soluble in acetone. The molar conductance measurement [Table 3] of the complex compounds in.

  4. Coenzyme Q10 prevented full blown splenomegaly and decreased melarsoprol-induced reactive encephalopathy in mice infected with Trypanosoma brucei rhodesiense

    Directory of Open Access Journals (Sweden)

    James Nyabuga Nyariki

    2015-03-01

    Full Text Available Objective: To establish the modulatory effects of coenzyme Q10 on experimental trypanosome infections in mice and evaluate the risk of occurrence and severity of melarsoprol-induced post treatment reactive encephalopathy (PTRE. Methods: Female Swiss white mice were orally administered with 200 mg/kg of coenzyme Q10 after which they were intraperitoneally inoculated with Trypanasoma brucei rhodesiense (T. b. rhodesiense. The resultant infection was allowed to develop and simulate all phases of human African trypanosomiasis and PTRE. Parasitaemia development, packed cell volume, haematological and pathological changes were determined. Results: A histological study in the brain tissue of T. b. rhodesiense infected mice demonstrated neuroinflammatory pathology which was highly amplified in the PTRE-induced groups. A prominent reduction in the severity of the neuroinflammatory response was detected when coenzyme-Q10 was administered. Furthermore, the mean tissue weight of spleen to body ratio in coenzyme Q10 supplemented group was significantly (P<0.05 different compared to un-supplemented groups, and clearly indicated that coenzyme Q10 prevented full blown splenomegaly pathogenesis by T. b. rhodesiense. A significant (P<0.05 increase in hemoglobin levels and red blood cells was observed in coenzyme Q10 mice compared to those infected and un-supplemented with coenzyme Q10. Conclusions: The capacity of coenzyme Q10 to alter the pathogenesis of T. b. rhodesiense infection in mice and following treatment with melarsoprol, may find application by rendering humans and animals less susceptible to deleterious effects of trypanosome infection such as splenomegaly and melarsoprol-induced PTRE and neurotoxicity.

  5. The Protective Effects of Alpha-Lipoic Acid and Coenzyme Q10 Combination on Ovarian Ischemia-Reperfusion Injury: An Experimental Study

    Directory of Open Access Journals (Sweden)

    Ahmet Ali Tuncer

    2016-01-01

    Full Text Available Objective. This study aims to evaluate whether alpha-lipoic acid and/or coenzyme Q10 can protect the prepubertal ovarian tissue from ischemia-reperfusion injury in an experimental rat model of ovarian torsion. Materials and Methods. Forty-two female preadolescent Wistar-Albino rats were divided into 6 equal groups randomly. The sham group had laparotomy without torsion; the other groups had torsion/detorsion procedure. After undergoing torsion, group 2 received saline, group 3 received olive oil, group 4 received alpha-lipoic acid, group 5 received coenzyme Q10, and group 6 received both alpha-lipoic acid and coenzyme Q10 orally. The oxidant-antioxidant statuses of these groups were compared using biochemical measurement of oxidized/reduced glutathione, glutathione peroxidase and malondialdehyde, pathological evaluation of damage and apoptosis within the ovarian tissue, and immunohistochemical assessment of nitric oxide synthase. Results. The left ovaries of the alpha-lipoic acid + coenzyme Q10 group had significantly lower apoptosis scores and significantly higher nitric oxide synthase content than the left ovaries of the control groups. The alpha-lipoic acid + coenzyme Q10 group had significantly higher glutathione peroxidase levels and serum malondialdehyde concentrations than the sham group. Conclusions. The combination of alpha-lipoic acid and coenzyme Q10 has beneficial effects on oxidative stress induced by ischemia-reperfusion injury related to ovarian torsion.

  6. Acyl-coenzyme A oxidases 1 and 3 in brown trout (Salmo trutta f. fario): Can peroxisomal fatty acid β-oxidation be regulated by estrogen signaling?

    Science.gov (United States)

    Madureira, Tânia Vieira; Castro, L Filipe C; Rocha, Eduardo

    2016-02-01

    Acyl-coenzyme A oxidases 1 (Acox1) and 3 (Acox3) are key enzymes in the regulation of lipid homeostasis. Endogenous and exogenous factors can disrupt their normal expression/activity. This study presents for the first time the isolation and characterization of Acox1 and Acox3 in brown trout (Salmo trutta f. fario). Additionally, as previous data point to the existence of a cross-talk between two nuclear receptors, namely peroxisome proliferator-activated receptors and estrogen receptors, it was here evaluated after in vitro exposures of trout hepatocytes the interference caused by ethynylestradiol in the mRNA levels of an inducible (by peroxisome proliferators) and a non-inducible oxidase. The isolated Acox1 and Acox3 show high levels of sequence conservation compared to those of other teleosts. Additionally, it was found that Acox1 has two alternative splicing isoforms, corresponding to 3I and 3II isoforms of exon 3 splicing variants. Both isoforms display tissue specificity, with Acox1-3II presenting a more ubiquitous expression in comparison with Acox1-3I. Acox3 was expressed in almost all brown trout tissues. According to real-time PCR data, the highest estrogenic stimulus was able to cause a down-regulation of Acox1 and an up-regulation of Acox3. So, for Acox1 we found a negative association between an estrogenic input and a directly activated PPARα target gene. In conclusion, changes in hormonal estrogenic stimulus may impact the mobilization of hepatic lipids to the gonads, with ultimate consequences in reproduction. Further studies using in vivo assays will be fundamental to clarify these issues.

  7. Effect of particle size on solubility, dissolution rate, and oral bioavailability: evaluation using coenzyme Q10 as naked nanocrystals

    Directory of Open Access Journals (Sweden)

    Sun J

    2012-11-01

    Full Text Available Jiao Sun,1 Fan Wang,1,2 Yue Sui,1 Zhennan She,1 Wenjun Zhai,1 Chunling Wang,1 Yihui Deng11College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China; 2Beijing Zhijianjinrui Applied Pharmaceutical Science Inc, Beijing, ChinaAbstract: In this paper work, four naked nanocrystals (size range 80–700 nm were prepared without any surfactant or polymer using the solvent/nonsolvent method. The effects of particle size on their solubility, dissolution, and oral bioavailability were investigated. Solubility and dissolution testing were performed in three types of dissolution medium, and the studies demonstrated that the equilibrium solubilities of coenzyme Q10 nanocrystals and bulk drugs were not affected by the dissolution media but the kinetic solubilities were. Kinetic solubility curves and changes in particle size distribution were determined and well explained by the proposed solubilization model for the nanocrystals and bulk drugs. The particle size effect on dissolution was clearly influenced by the diffusion coefficients of the various dissolution media, and the dissolution velocity of coenzyme Q10 increased as particle size decreased. The bioavailability of coenzyme Q10 after oral administration in beagle dogs was improved by reducing the particle size. For 700 nm nanocrystals, the AUC0–48 was 4.4-fold greater than that for the coarse suspensions, but a further decrease in particle size from 700 nm to 120 nm did not contribute to improvement in bioavailability until the particle size was reduced to 80 nm, when bioavailability was increased by 7.3-fold.Keywords: particle size, solubility, dissolution, nanocrystal, bioavailability, coenzyme Q10

  8. Effect of the additives on clouding behavior and thermodynamics of coenzyme Q10-Kolliphor HS15 micelle aqueous solutions

    Science.gov (United States)

    Hu, Li; Zhang, Jing; Zhu, Chao; Pan, Hong-chun; Liu, Hong

    2017-11-01

    Herein we investigate the effect of different additives (electrolytes, amino acids, PEG, and sugars) on the cloud points (CP) of coenzyme Q10 (CoQ10) - Kolliphor HS15 (HS15) micelle aqueous solutions. The CP values were decreased with the increase of electrolytes and sugars, following: CPAl3+ reduced the CP. A depression of CP for CoQ10-HS15 micelle solution with PEG was molecular weight of PEG dependent. The significant thermodynamic parameters were also evaluated and discussed.

  9. ORF Sequence: NC_003103 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available etoacid-coenzyme A transferase [Rickettsia conorii str. Malish 7] MGIPAFYTKTGIGTIVEEGKATKEFNGKKYIMETALQADLAIIKGFKADKSSNVIYNKTARNFNAVM...AGAAKVTVCEVEEIVKVGELDPNNIHTPNIFIQRLIVGEKYEKRIEQLTVREK

  10. A randomized trial of coenzyme Q10 in patients with confirmed statin myopathy.

    Science.gov (United States)

    Taylor, Beth A; Lorson, Lindsay; White, C Michael; Thompson, Paul D

    2015-02-01

    Coenzyme Q10 (CoQ10) supplementation is the most popular therapy for statin myalgia among both physicians and patients despite limited and conflicting evidence of its efficacy. This study examined the effect of coenzyme Q10 (CoQ10) supplementation on simvastatin-associated muscle pain, muscle strength and aerobic performance in patients with confirmed statin myalgia. Statin myalgia was confirmed in 120 patients with prior symptoms of statin myalgia using an 8-week randomized, double-blind crossover trial of simvastatin 20 mg/d and placebo. Forty-one subjects developed muscle pain with simvastatin but not with placebo and were randomized to simvastatin 20 mg/d combined with CoQ10 (600 mg/d ubiquinol) or placebo for 8 weeks. Muscle pain (Brief Pain Inventory [BPI]), time to pain onset, arm and leg muscle strength, and maximal oxygen uptake (VO2max) were measured before and after each treatment. Serum CoQ10 increased from 1.3 ± 0.4 to 5.2 ± 2.3 mcg/mL with simvastatin and CoQ10, but did not increase with simvastatin and placebo (1.3 ± 0.3 to 0.8 ± 0.2) (p pain severity and interference scores increased with simvastatin therapy (both p muscle strength or VO2max with simvastatin with or without CoQ10 (all p > 0.10). Marginally more subjects reported pain with CoQ10 (14 of 20 vs 7 of 18; p = 0.05). There was no difference in time to pain onset in the CoQ10 (3.0 ± 2.0 weeks) vs. placebo (2.4 ± 2.1 wks) groups (p = 0.55). A similar lack of CoQ10 effect was observed in 24 subjects who were then crossed over to the alternative treatment. Only 36% of patients complaining of statin myalgia develop symptoms during a randomized, double-blind crossover of statin vs placebo. CoQ10 supplementation does not reduce muscle pain in patients with statin myalgia. Trial RegistrationNCT01140308; www.clinicaltrials.gov. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Nanoencapsulation of coenzyme Q10 and vitamin E acetate protects against UVB radiation-induced skin injury in mice.

    Science.gov (United States)

    Pegoraro, Natháli S; Barbieri, Allanna V; Camponogara, Camila; Mattiazzi, Juliane; Brum, Evelyne S; Marchiori, Marila C L; Oliveira, Sara M; Cruz, Letícia

    2017-02-01

    This study aimed to investigate the feasibility of producing semisolid formulations based on nanocapsule suspensions containing the association of the coenzyme Q10 and vitamin E acetate by adding gellan gum (2%) to the suspensions. Furthermore, we studied their application as an alternative for the treatment of inflammation induced by ultraviolet B (UVB) radiation. For this, an animal model of injury induced by UVB-radiation was employed. All semisolids presented pH close to 5.5, drug content above 95% and mean diameter on the nanometric range, after redispersion in water. Besides, the semisolids presented non-Newtonian flow with pseudoplastic behavior and suitable spreadability factor values. The results also showed that the semisolid containing coenzyme Q10-loaded nanocapsules with higher vitamin E acetate concentration reduced in 73±8% the UVB radiation-induced ear edema. Moreover, all formulations tested were able to reduce inflammation parameters evaluated through MPO activity and histological procedure on injured tissue and the semisolids containing the nanoencapsulated coenzyme Q10 reduced oxidative parameters assessment through the non-protein thiols levels and lipid peroxidation. This way, the semisolids based on nanocapsules may be considered a promising approach for the treatment and prevention of skin inflammation diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. High-Throughput Screening of Coenzyme Preference Change of Thermophilic 6-Phosphogluconate Dehydrogenase from NADP(+) to NAD(.).

    Science.gov (United States)

    Huang, Rui; Chen, Hui; Zhong, Chao; Kim, Jae Eung; Zhang, Yi-Heng Percival

    2016-09-02

    Coenzyme engineering that changes NAD(P) selectivity of redox enzymes is an important tool in metabolic engineering, synthetic biology, and biocatalysis. Here we developed a high throughput screening method to identify mutants of 6-phosphogluconate dehydrogenase (6PGDH) from a thermophilic bacterium Moorella thermoacetica with reversed coenzyme selectivity from NADP(+) to NAD(+). Colonies of a 6PGDH mutant library growing on the agar plates were treated by heat to minimize the background noise, that is, the deactivation of intracellular dehydrogenases, degradation of inherent NAD(P)H, and disruption of cell membrane. The melted agarose solution containing a redox dye tetranitroblue tetrazolium (TNBT), phenazine methosulfate (PMS), NAD(+), and 6-phosphogluconate was carefully poured on colonies, forming a second semi-solid layer. More active 6PGDH mutants were examined via an enzyme-linked TNBT-PMS colorimetric assay. Positive mutants were recovered by direct extraction of plasmid from dead cell colonies followed by plasmid transformation into E. coli TOP10. By utilizing this double-layer screening method, six positive mutants were obtained from two-round saturation mutagenesis. The best mutant 6PGDH A30D/R31I/T32I exhibited a 4,278-fold reversal of coenzyme selectivity from NADP(+) to NAD(+). This screening method could be widely used to detect numerous redox enzymes, particularly for thermophilic ones, which can generate NAD(P)H reacted with the redox dye TNBT.

  13. Spectrofluorimetric determination of trace amount of coenzyme II using ciprofloxacin-terbium complex as a fluorescent probe

    International Nuclear Information System (INIS)

    Bian Weiwei; Wang Yusheng; Zhu Xiaojing; Jiang Chongqiu

    2006-01-01

    A new spectrofluorimetric method was developed for the determination of trace amount of nicotinamide adenine dinucleotide phosphate (NADP). Using terbium ion (Tb 3+ )-ciprofloxacin (CIP) complex as a fluorescent probe, in the buffer solution of pH=9.00, NADP can remarkably enhance the fluorescence intensity of the Tb 3+ -CIP complex at λ=545nm and the enhanced fluorescence intensity of Tb 3+ ion is in proportion to the concentration of NADP. Optimum conditions for the determination of NADP were also investigated. The dynamic range for the determination of NADP is 4.9x10 -7 -3.7x10 -6 molL -1 with detection limit of 1.3x10 -7 molL -1 . This method is simple, practical and relatively free interference from coexisting substances and can be successfully applied to determination of NADP in synthetic water samples. Moreover, the enhancement mechanisms of the fluorescence intensity in the Tb 3+ -CIP system and the Tb 3+ -CIP-NADP system have been also discussed

  14. Photoionization of oxidized coenzyme Q in microemulsion: laser flash photolysis study in biomembrane-like system.

    Science.gov (United States)

    Li, Kun; Wang, Mei; Wang, Jin; Zhu, Rongrong; Sun, Dongmei; Sun, Xiaoyu; Wang, Shi-Long

    2013-01-01

    Photoexcitation to generate triplet state has been proved to be the main photoreaction in homogeneous system for many benzoquinone derivatives, including oxidized coenzyme Q (CoQ) and its analogs. In the present study, microemulsion of CoQ, a heterogeneous system, is employed to mimic the distribution of CoQ in biomembrane. The photochemistry of CoQ(10) in microemulsion and cyclohexane is investigated and compared using laser flash photolysis and results show that CoQ(10) undergoes photoionization via a monophotonic process to generate radical cation of CoQ(10) in microemulsion and photoexcitation to generate excited triplet state in cyclohexane. Meanwhile, photoreactions of duroquinone (DQ) and CoQ(0) in microemulsion are also investigated to analyze the influence of molecular structure on the photochemistry of benzoquinone derivatives in microemulsion. Results suggest that photoexcitation, which is followed by excited state-involved hydrogen-abstraction reaction, is the main photoreaction for DQ and CoQ(0) in microemulsion. However, photoexcited CoQ(0) also leads to the formation of hydrated electrons. The isoprenoid side chain-involved high resonance stabilization is proposed to explain the difference in photoreactions of CoQ(0) and CoQ(10) in microemulsion. Considering that microemulsion is close to biomembrane system, its photoionization in microemulsion may be helpful to understand the real photochemistry of biological quinones in biomembrane system. © 2012 Tongji University. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

  15. Coenzyme Q10 partially restores pathological alterations in a macrophage model of Gaucher disease.

    Science.gov (United States)

    de la Mata, Mario; Cotán, David; Oropesa-Ávila, Manuel; Villanueva-Paz, Marina; de Lavera, Isabel; Álvarez-Córdoba, Mónica; Luzón-Hidalgo, Raquel; Suárez-Rivero, Juan M; Tiscornia, Gustavo; Sánchez-Alcázar, José A

    2017-02-06

    Gaucher disease (GD) is caused by mutations in the GBA1 gene which encodes lysosomal β-glucocerebrosidase (GCase). In GD, partial or complete loss of GCase activity causes the accumulation of the glycolipids glucosylceramide (GlcCer) and glucosylsphingosine in the lysosomes of macrophages. In this manuscript, we investigated the effects of glycolipids accumulation on lysosomal and mitochondrial function, inflammasome activation and efferocytosis capacity in a THP-1 macrophage model of Gaucher disease. In addition, the beneficial effects of coenzyme Q 10 (CoQ) supplementation on cellular alterations were evaluated. Chemically-induced Gaucher macrophages were developed by differentiateing THP-1 monocytes to macrophages by treatment with phorbol 12-myristate 13-acetate (PMA) and then inhibiting intracellular GCase with conduritol B-epoxide (CBE), a specific irreversible inhibitor of GCase activity, and supplementing the medium with exogenous GlcCer. This cell model accumulated up to 16-fold more GlcCer compared with control THP-1 cells. Chemically-induced Gaucher macrophages showed impaired autophagy flux associated with mitochondrial dysfunction and increased oxidative stress, inflammasome activation and impaired efferocytosis. All abnormalities were partially restored by supplementation with CoQ. These data suggest that targeting mitochondria function and oxidative stress by CoQ can ameliorate the pathological phenotype of Gaucher cells. Chemically-induced Gaucher macrophages provide cellular models that can be used to investigate disease pathogenesis and explore new therapeutics for GD.

  16. Bioavailability enhancement of coenzyme Q10: an extensive review of patents.

    Science.gov (United States)

    Beg, Sarwar; Javed, Shamama; Kohli, Kanchan

    2010-11-01

    Coenzyme Q10 (CoQ10) is a major antioxidant principle found in human body which plays a vital role in maintaining several biochemical pathways of body. It acts as a potential mediator in transferring electrons in oxidoreductive reactions of electron transport chain. Chemically, it is a basic quinone containing moiety having a large and high molecular weight structure. Deficiency of this in body leads to several potential disorders like dysfunctions in cellular energetics, neurological degeneration, higher oxidative stress induced damage, breast cancer etc. The high molecular weight and lipophilicity of CoQ10 makes it poorly water soluble and consequently leads to low systemic availability. Several advancements have been made to enhance the bioavailability of CoQ10 using various approaches like size reduction, solubility enhancement (by solid dispersion, prodrug, complexation, ionization) and use of novel drug carriers such as liposomes, microspheres, nanoparticles, nanoemulsions and self-emulsifying system. The primary objective of the present review is to assemble patents representing the various approaches used for enhancement of CoQ10 bioavailability.

  17. Coenzyme B12 synthesis as a baseline to study metabolite contribution of animal microbiota.

    Science.gov (United States)

    Danchin, Antoine; Braham, Sherazade

    2017-07-01

    Microbial communities thrive in a number of environments. Exploration of their microbiomes - their global genome - may reveal metabolic features that contribute to the development and welfare of their hosts, or chemical cleansing of environments. Yet we often lack final demonstration of their causal role in features of interest. The reason is that we do not have proper baselines that we could use to monitor how microbiota cope with key metabolites in the hosting environment. Here, focusing on animal gut microbiota, we describe the fate of cobalamins - metabolites of the B12 coenzyme family - that are essential for animals but synthesized only by prokaryotes. Microbiota produce the vitamin used in a variety of animals (and in algae). Coprophagy plays a role in its management. For coprophobic man, preliminary observations suggest that the gut microbial production of vitamin B12 plays only a limited role. By contrast, the vitamin is key for structuring microbiota. This implies that it is freely available in the environment. This can only result from lysis of the microbes that make it. A consequence for biotechnology applications is that, if valuable for their host, B12-producing microbes should be sensitive to bacteriophages and colicins, or make spores. © 2017 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  18. Cofilin/Twinstar phosphorylation levels increase in response to impaired coenzyme a metabolism.

    Directory of Open Access Journals (Sweden)

    Katarzyna Siudeja

    Full Text Available Coenzyme A (CoA is a pantothenic acid-derived metabolite essential for many fundamental cellular processes including energy, lipid and amino acid metabolism. Pantothenate kinase (PANK, which catalyses the first step in the conversion of pantothenic acid to CoA, has been associated with a rare neurodegenerative disorder PKAN. However, the consequences of impaired PANK activity are poorly understood. Here we use Drosophila and human neuronal cell cultures to show how PANK deficiency leads to abnormalities in F-actin organization. Cells with reduced PANK activity are characterized by abnormally high levels of phosphorylated cofilin, a conserved actin filament severing protein. The increased levels of phospho-cofilin coincide with morphological changes of PANK-deficient Drosophila S2 cells and human neuronal SHSY-5Y cells. The latter exhibit also markedly reduced ability to form neurites in culture--a process that is strongly dependent on actin remodeling. Our results reveal a novel and conserved link between a metabolic biosynthesis pathway, and regulation of cellular actin dynamics.

  19. Coenzyme Q10 Levels Are Decreased in the Cerebellum of Multiple-System Atrophy Patients.

    Directory of Open Access Journals (Sweden)

    Lucia V Schottlaender

    Full Text Available The objective of this study was to evaluate whether the levels of coenzyme Q10 (CoQ10 in brain tissue of multiple system atrophy (MSA patients differ from those in elderly controls and in patients with other neurodegenerative diseases.Flash frozen brain tissue of a series of 20 pathologically confirmed MSA patients [9 olivopontocerebellar atrophy (OPCA type, 6 striatonigral degeneration (SND type, and 5 mixed type] was used for this study. Elderly controls (n = 37 as well as idiopathic Parkinson's disease (n = 7, dementia with Lewy bodies (n = 20, corticobasal degeneration (n = 15 and cerebellar ataxia (n = 18 patients were used as comparison groups. CoQ10 was measured in cerebellar and frontal cortex tissue by high performance liquid chromatography.We detected a statistically significant decrease (by 3-5% in the level of CoQ10 in the cerebellum of MSA cases (P = 0.001, specifically in OPCA (P = 0.001 and mixed cases (P = 0.005, when compared to controls as well as to other neurodegenerative diseases [dementia with Lewy bodies (P<0.001, idiopathic Parkinson's disease (P<0.001, corticobasal degeneration (P<0.001, and cerebellar ataxia (P = 0.001].Our results suggest that a perturbation in the CoQ10 biosynthetic pathway is associated with the pathogenesis of MSA but the mechanism behind this finding remains to be elucidated.

  20. Effect of Coenzyme-Q10 on Doxorubicin-Induced Nephrotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Azza A. K. El-Sheikh

    2012-01-01

    Full Text Available Nephrotoxicity is one of the limiting factors for using doxorubicin (Dox as an anticancer chemotherapeutic. Here, we investigated possible protective effect of coenzyme-Q10 (CoQ10 on Dox-induced nephrotoxicity and the mechanisms involved. Two doses (10 and 100 mg/kg of CoQ10 were administered orally to rats for 8 days, in the presence or absence of nephrotoxicity induced by a single intraperitoneal injection of Dox (15 mg/kg at day 4 of the experiment. Our results showed that the low dose of CoQ10 succeeded in reversing Dox-induced nephrotoxicity to control levels (e.g., levels of blood urea nitrogen and serum creatinine, concentrations of renal reduced glutathione (GSH and malondialdehyde, catalase activity and caspase 3 expression, and renal histopathology. Alternatively, the high dose of CoQ10 showed no superior nephroprotection over the low dose, as there were no significant improvements in renal histopathology, catalase activity, or caspase 3 expression compared to the Dox-treated group. Interestingly, the high dose of CoQ10 alone significantly decreased renal GSH level as well as catalase activity and caused a mild induction of caspase 3 expression compared to control, probably due to a prooxidant effect at this dose of CoQ10. We conclude that CoQ10 protects from Dox-induced nephrotoxicity with a precaution to dosage adjustment.

  1. Preformed β-amyloid fibrils are destabilized by coenzyme Q10 in vitro

    International Nuclear Information System (INIS)

    Ono, Kenjiro; Hasegawa, Kazuhiro; Naiki, Hironobu; Yamada, Masahito

    2005-01-01

    Inhibition of the formation of β-amyloid fibrils (fAβ), as well as the destabilization of preformed fAβ in the CNS, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that nordihydroguaiaretic acid (NDGA) and wine-related polyphenol, myricetin (Myr), inhibit fAβ formation from Aβ and destabilize preformed fAβ in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of coenzyme Q 10 (CoQ 10 ) on the formation, extension, and destabilization of fAβ at pH 7.5 at 37 deg C in vitro. We next compared the anti-amyloidogenic activities of CoQ 10 with NDGA and Myr. CoQ 10 dose-dependently inhibited fAβ formation from amyloid β-peptide (Aβ), as well as their extension. Moreover, it destabilized preformed fAβs. The anti-amyloidogenic effects of CoQ 10 were slightly weaker than those of NDGA and Myr. CoQ 10 could be a key molecule for the development of therapeutics for AD

  2. Application of Coenzyme Q10 for Accelerating Soft Tissue Wound Healing after Tooth Extraction in Rats

    Directory of Open Access Journals (Sweden)

    Toshiki Yoneda

    2014-12-01

    Full Text Available Accelerating wound healing after tooth extraction is beneficial in dental treatment. Application of antioxidants, such as reduced coenzyme Q10 (rCoQ10, may promote wound healing after tooth extraction. In this study, we examined the effects of topical application of rCoQ10 on wound healing after tooth extraction in rats. After maxillary first molars were extracted, male Fischer 344 rats (8 weeks old (n = 27 received topical application of ointment containing 5% rCoQ10 (experimental group or control ointment (control group to the sockets for 3 or 8 days (n = 6–7/group. At 3 days after extraction, the experimental group showed higher collagen density and lower numbers of polymorphonuclear leukocytes in the upper part of socket, as compared to the control group (p < 0.05. Gene expression of interleukin-1β, tumor necrosis factor-α and nuclear factor-κB were also lower in the experimental group than in the control group (p < 0.05. At 8 days after tooth extraction, there were no significant differences in collagen density, number of polymorphonuclear leukocytes and bone fill between the groups. Our results suggest that topical application of rCoQ10 promotes wound healing in the soft tissue of the alveolar socket, but that rCoQ10 has a limited effect on bone remodeling in rats.

  3. Interaction of coenzyme Q10 with the intestinal drug transporter P-glycoprotein.

    Science.gov (United States)

    Itagaki, Shirou; Ochiai, Akiko; Kobayashi, Masaki; Sugawara, Mitsuru; Hirano, Takeshi; Iseki, Ken

    2008-08-27

    In clinical trials, patients usually take many kinds of drugs at the same time. Thus, drug-drug interactions can often directly affect the therapeutic safety and efficacy of many drugs. Oral delivery is the most desirable means of drug administration. Changes in the activity of drug transporters may substantially influence the absorption of administered drugs from the intestine. However, there have been a few studies on food-drug interactions involving transporters. It is important to be aware of the potential of food-drug interactions and to act in order to prevent undesirable and harmful clinical consequences. Coenzyme Q10 (CoQ10) is very widely consumed by humans as a food supplement because of its recognition by the public as an important nutrient in supporting human health. Since intestinal efflux transporter P-glycoprotein (P-gp) is one of the major factors in drug-drug interactions, we focused on this transporter. We report here for the first time that CoQ10, which is widely used as a food supplement, affects the transport activity of P-gp.

  4. Engineered Production of Short-Chain Acyl-Coenzyme A Esters in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Krink-Koutsoubelis, Nicolas; Loechner, Anne C.; Lechner, Anna

    2018-01-01

    Short-chain acyl-coenzyme A esters serve as intermediate compounds in fatty acid biosynthesis, and the production of polyketides, biopolymers and other value-added chemicals. S. cerevisiae is a model organism that has been utilized for the biosynthesis of such biologically and economically valuable...... compounds. However, its limited repertoire of short-chain acyl-CoAs effectively prevents its application as a production host for a plethora of natural products. Therefore, we introduced biosynthetic metabolic pathways to five different acyl-CoA esters into S. cerevisiae. Our engineered strains provide......-CoA at 0.5 μM; and isovaleryl-CoA, n-butyryl-CoA, and n-hexanoyl-CoA at 6 μM each. The acyl-CoAs produced in this study are common building blocks of secondary metabolites and will enable the engineered production of a variety of natural products in S. cerevisiae. By providing this toolbox of acyl...

  5. Acute Hypoglycemia Induces Painful Neuropathy and the Treatment of Coenzyme Q10

    Directory of Open Access Journals (Sweden)

    Yan Ping Zhang

    2016-01-01

    Full Text Available Diabetic neuropathic pain is reduced with tight glycemic control. However, strict control increases the risk of hypoglycemic episodes, which are themselves linked to painful neuropathy. This study explored the effects of hypoglycemia-related painful neuropathy. Pretreatment with coenzyme Q10 (CoQ10 was performed to explore the preventive effect of CoQ10 on hypoglycemia-related acute neuropathic pain. Two strains of mice were used and 1 unit/kg of insulin was given to induce hypoglycemia. Mechanical sensitivity of hindpaw withdrawal thresholds was measured using von Frey filaments. Blood glucose levels were clamped at normal levels by joint insulin and glucose injection to test whether insulin itself induced hypersensitivity. Results suggest that the increased mechanical sensitivity after insulin injection is related to decreased blood glucose levels. When blood glucose levels remained at a normal level by the linked administration of insulin and glucose, mice demonstrated no significant change in mechanical sensitivity. Pretreatment with CoQ10 prevented neuropathic pain and the expression of the stress factor c-Fos. These results support the concept that pain in the diabetic scenario can be the result of hypoglycemia and not insulin itself. Additionally, pretreatment with CoQ10 may be a potent preventive method for the development of neuropathic pain.

  6. Preparation, characterization and in silico modeling of biodegradable nanoparticles containing cyclosporine A and coenzyme Q10

    Energy Technology Data Exchange (ETDEWEB)

    Ankola, D D; Ravi Kumar, M N V [Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow, G4 0NR (United Kingdom); Durbin, E W [Department of Physics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106 (United States); Buxton, G A [Department of Sciences, Robert Morris University, 6001 University Boulevard, Moon Township, PA 15108 (United States); Schaefer, J; Bakowsky, U, E-mail: mnvrkumar@strath.ac.uk [Department of Pharmaceutics and Biopharmacy, Philipps Universitt, 35037 Marburg (Germany)

    2010-02-10

    Combination therapy will soon become a reality, particularly for those patients requiring poly-therapy to treat co-existing disease states. This becomes all the more important with the increasing cost, time and complexity of the drug discovery process prompting one to look at new delivery systems to increase the efficacy, safety and patient compliance of existing drugs. Along this line, we attempted to design nano-scale systems for simultaneous encapsulation of cyclosporine A (CsA) and coenzyme Q10 (CoQ10) and model their encapsulation and release kinetics. The in vitro characterization of the co-encapsulated nanoparticles revealed that the surfactant nature, concentration, external phase volume, droplet size reduction method and drug loading concentration can all influence the overall performance of the nanoparticles. The semi-quantitative solubility study indicates the strong influence of CoQ10 on CsA entrapment which was thought to be due to an increase in the lipophilicity of the overall system. The in vitro dissolution profile indicates the influence of CoQ10 on CsA release (64%) to that of individual particles of CsA, where the release is faster and higher (86%) on 18th day. The attempts to model the encapsulation and release kinetics were successful, offering a possibility to use such models leading to high throughput screening of drugs and their nature, alone or in combination for a particular polymer, if chi-parameters are understood.

  7. Serum Levels of Coenzyme Q10 in Patients with Multiple System Atrophy.

    Directory of Open Access Journals (Sweden)

    Takashi Kasai

    Full Text Available The COQ2 gene encodes an essential enzyme for biogenesis, coenzyme Q10 (CoQ10. Recessive mutations in this gene have recently been identified in families with multiple system atrophy (MSA. Moreover, specific heterozygous variants in the COQ2 gene have also been reported to confer susceptibility to sporadic MSA in Japanese cohorts. These findings have suggested the potential usefulness of CoQ10 as a blood-based biomarker for diagnosing MSA. This study measured serum levels of CoQ10 in 18 patients with MSA, 20 patients with Parkinson's disease and 18 control participants. Although differences in total CoQ10 (i.e., total levels of serum CoQ10 and its reduced form among the three groups were not significant, total CoQ10 level corrected by serum cholesterol was significantly lower in the MSA group than in the Control group. Our findings suggest that serum CoQ10 can be used as a biomarker in the diagnosis of MSA and to provide supportive evidence for the hypothesis that decreased levels of CoQ10 in brain tissue lead to an increased risk of MSA.

  8. Coenzyme Q10 and soyphosphatidylcholine in EK extender on preservation of Rhode Island Red poultry semen

    Directory of Open Access Journals (Sweden)

    Amit Kumar Nath

    2015-06-01

    Full Text Available The objective of this study was to evaluate the efficacy of EK extender alone or incorporation with CoenzymeQ10 (CoQ10 and/or soyphosphatidylcholine (SPC in poultry semen and their effects on seminal traits during temporal storage at 4⁰C for different time intervals (12 h, 24 h, and 36 h. Heterospermic pooled semen samples diluted (1:4 with EK, EK + SPC, EK+ CoQ10 and EK + SPC + CoQ10 extenders separately, preserved and different spermiogram were assessed. Various seminal traits within the same extender differ significantly (p<0.05 among different groups and with different time intervals of storage. CoQ10 and SPC in the EK extender exhibited favorable synergistic effect on sperm quality and were able to protect the male gametes against cold-stress up to 36h at 4⁰C. In this study, we concluded that incorporation of SPC and CoQ10 together in EK extender possess novel potentiality to maintain seminal quality during liquid storage of poultry semen at 4⁰C and for their safe transportation and further use for Artificial Reproductive technologies (ARTs.

  9. The TIP30 protein complex, arachidonic acid and coenzyme A are required for vesicle membrane fusion.

    Directory of Open Access Journals (Sweden)

    Chengliang Zhang

    Full Text Available Efficient membrane fusion has been successfully mimicked in vitro using artificial membranes and a number of cellular proteins that are currently known to participate in membrane fusion. However, these proteins are not sufficient to promote efficient fusion between biological membranes, indicating that critical fusogenic factors remain unidentified. We have recently identified a TIP30 protein complex containing TIP30, acyl-CoA synthetase long-chain family member 4 (ACSL4 and Endophilin B1 (Endo B1 that promotes the fusion of endocytic vesicles with Rab5a vesicles, which transport endosomal acidification enzymes vacuolar (H⁺-ATPases (V-ATPases to the early endosomes in vivo. Here, we demonstrate that the TIP30 protein complex facilitates the fusion of endocytic vesicles with Rab5a vesicles in vitro. Fusion of the two vesicles also depends on arachidonic acid, coenzyme A and the synthesis of arachidonyl-CoA by ACSL4. Moreover, the TIP30 complex is able to transfer arachidonyl groups onto phosphatidic acid (PA, producing a new lipid species that is capable of inducing close contact between membranes. Together, our data suggest that the TIP30 complex facilitates biological membrane fusion through modification of PA on membranes.

  10. Reduction and Methyl Transfer Kinetics of the Alpha Subunit from Acetyl-Coenzyme A Synthase

    Energy Technology Data Exchange (ETDEWEB)

    Xiangshi Tan; Christopher Sewell; Qingwu Yang; Paul A. Lindahl

    2003-01-15

    OAK-B135 Stopped-flow was used to evaluate the methylation and reduction kinetics of the isolated alpha subunit of acetyl-Coenzyme A synthase from Moorella thermoacetica. This catalytically active subunit contains a novel Ni-X-Fe4S4 cluster and a putative unidentified n =2 redox site called D. The D-site must be reduced for a methyl group to transfer from a corrinoid-iron-sulfur protein, a key step in the catalytic synthesis of acetyl-CoA. The Fe4S4 component of this cluster is also redox active, raising the possibility that it is the D-site or a portion thereof. Results presented demonstrate that the D-site reduces far faster than the Fe4S4 component, effectively eliminating this possibility. Rather, this component may alter catalytically important properties of the Ni center. The D-site is reduced through a pathway that probably does not involve the Fe4S4 component of this active-site cluster.

  11. Modeling of process parameters for enhanced production of coenzyme Q10 from Rhodotorula glutinis.

    Science.gov (United States)

    Balakumaran, Palanisamy Athiyaman; Meenakshisundaram, Sankaranarayanan

    2015-01-01

    Coenzyme Q10 (CoQ10) plays an indispensable role in ATP generation through oxidative phosphorylation and helps in scavenging superoxides generated during electron transfer reactions. It finds extensive applications specifically related to oxidative damage and metabolic dysfunctions. This article reports the use of a statistical approach to optimize the concentration of key variables for the enhanced production of CoQ10 by Rhodotorula glutinis in a lab-scale fermenter. The culture conditions that promote optimum growth and CoQ10 production were optimized and the interaction of significant variables para-hydroxybenzoic acid (PHB, 819.34 mg/L) and soybean oil (7.78% [v/v]) was studied using response surface methodology (RSM). CoQ10 production increased considerably from 10 mg/L (in control) to 39.2 mg/L in batch mode with RSM-optimized precursor concentration. In the fed-batch mode, PHB and soybean oil feeding strategy enhanced CoQ10 production to 78.2 mg/L.

  12. Dependence of Brown Adipose Tissue Function on CD36-Mediated Coenzyme Q Uptake

    Directory of Open Access Journals (Sweden)

    Courtney M. Anderson

    2015-02-01

    Full Text Available Brown adipose tissue (BAT possesses the inherent ability to dissipate metabolic energy as heat through uncoupled mitochondrial respiration. An essential component of the mitochondrial electron transport chain is coenzyme Q (CoQ. While cells synthesize CoQ mostly endogenously, exogenous supplementation with CoQ has been successful as a therapy for patients with CoQ deficiency. However, which tissues depend on exogenous CoQ uptake as well as the mechanism by which CoQ is taken up by cells and the role of this process in BAT function are not well understood. Here, we report that the scavenger receptor CD36 drives the uptake of CoQ by BAT and is required for normal BAT function. BAT from mice lacking CD36 displays CoQ deficiency, impaired CoQ uptake, hypertrophy, altered lipid metabolism, mitochondrial dysfunction, and defective nonshivering thermogenesis. Together, these data reveal an important new role for the systemic transport of CoQ to BAT and its function in thermogenesis.

  13. Water-soluble coenzyme Q10 formulation in presbycusis: long-term effects.

    Science.gov (United States)

    Guastini, Luca; Mora, Renzo; Dellepiane, Massimo; Santomauro, Valentina; Giorgio, Manini; Salami, Angelo

    2011-05-01

    These findings provide the basis for understanding the duration of the effect after the last use of the drug and encourage a larger clinical trial to collect additional evidence on the effect of coenzyme Q10 (CoQ10) in preventing the development of hearing loss in subjects with presbycusis. The aim of this study was to evaluate the long-term effects of a water-soluble formulation of CoQ10 (Q-TER) in subjects with presbycusis. Sixty patients with presbycusis were included and divided at random into three numerically equal groups. For 30 days, group A underwent therapy with Q-TER, group B underwent therapy with vitamin E, and group C received placebo. Before, at the end, and 6 months after the end of the treatment, all patients underwent evaluation of pure tone audiometry, transient evoked otoacoustic emissions and otoacoustic products of distortion, auditory brainstem response, and speech audiometry. Compared with group B, at the end of the treatment in group A the pure tone audiometry showed a significant (p < 0.05) improvement of the audiometric thresholds at 1000, 2000, 4000, and 8000 Hz. This improvement was confirmed by the speech audiometry and last check. We found no significant differences in the other parameters and in group C.

  14. Kaempferol increases levels of coenzyme Q in kidney cells and serves as a biosynthetic ring precursor.

    Science.gov (United States)

    Fernández-Del-Río, Lucía; Nag, Anish; Gutiérrez Casado, Elena; Ariza, Julia; Awad, Agape M; Joseph, Akil I; Kwon, Ohyun; Verdin, Eric; de Cabo, Rafael; Schneider, Claus; Torres, Jorge Z; Burón, María I; Clarke, Catherine F; Villalba, José M

    2017-09-01

    Coenzyme Q (Q) is a lipid-soluble antioxidant essential in cellular physiology. Patients with Q deficiencies, with few exceptions, seldom respond to treatment. Current therapies rely on dietary supplementation with Q 10 , but due to its highly lipophilic nature, Q 10 is difficult to absorb by tissues and cells. Plant polyphenols, present in the human diet, are redox active and modulate numerous cellular pathways. In the present study, we tested whether treatment with polyphenols affected the content or biosynthesis of Q. Mouse kidney proximal tubule epithelial (Tkpts) cells and human embryonic kidney cells 293 (HEK 293) were treated with several types of polyphenols, and kaempferol produced the largest increase in Q levels. Experiments with stable isotope 13 C-labeled kaempferol demonstrated a previously unrecognized role of kaempferol as an aromatic ring precursor in Q biosynthesis. Investigations of the structure-function relationship of related flavonols showed the importance of two hydroxyl groups, located at C3 of the C ring and C4' of the B ring, both present in kaempferol, as important determinants of kaempferol as a Q biosynthetic precursor. Concurrently, through a mechanism not related to the enhancement of Q biosynthesis, kaempferol also augmented mitochondrial localization of Sirt3. The role of kaempferol as a precursor that increases Q levels, combined with its ability to upregulate Sirt3, identify kaempferol as a potential candidate in the design of interventions aimed on increasing endogenous Q biosynthesis, particularly in kidney. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Bioavailability assessment of hydroxymethylglutaryl coenzyme A reductase inhibitor utilizing pulsatile drug delivery system: a pilot study.

    Science.gov (United States)

    Taha, Ehab I

    2016-09-01

    Chronotherapy or pulsatile drug delivery system could be achieved by increasing drug plasma concentration exactly at the time of disease incidence. Cholesterol synthesis shows a circadian rhythm being high at late night and early in the morning. Simvastatin (SIM) inhibits hydroxymethylglutaryl coenzyme A reductase, which is responsible for cholesterol synthesis. In this study, SIM lipid-based formulation filled in gelatin capsules and coated with aqueous Eudragit® S100 dispersion was prepared for chronotherapeutic treatment of hypercholesterolemia. The pharmacokinetic parameters of SIM capsules were studied in human volunteers after a single oral dose and compared with that of Zocor® tablets as a reference in a randomized cross-over study. Pharmacokinetic parameters such as AUC 0-∞ , C max , T max , t 1/2 and elimination rate constant were determined from plasma concentration-time profile for both formulations. The tested formulation had the ability to delay drug absorption and provide higher drug concentrations from 3 up to 10 h after oral administration compared to that of commercial tablets. The data in this study revealed that the prepared formulation could be effective in chronotherapeutic treatment of hypercholesterolemia. Moreover, the tested formulation was found to enhance SIM bioavailability by 29% over the reference tablets.

  16. Micronutrient special issue: Coenzyme Q10 requirements for DNA damage prevention

    International Nuclear Information System (INIS)

    Schmelzer, Constance; Döring, Frank

    2012-01-01

    Coenzyme Q 10 (CoQ 10 ) is an essential component for electron transport in the mitochondrial respiratory chain and serves as cofactor in several biological processes. The reduced form of CoQ 10 (ubiquinol, Q 10 H 2 ) is an effective antioxidant in biological membranes. During the last years, particular interest has been grown on molecular effects of CoQ 10 supplementation on mechanisms related to DNA damage prevention. This review describes recent advances in our understanding about the impact of CoQ 10 on genomic stability in cells, animals and humans. With regard to several in vitro and in vivo studies, CoQ 10 provides protective effects on several markers of oxidative DNA damage and genomic stability. In comparison to the number of studies reporting preventive effects of CoQ 10 on oxidative stress biomarkers, CoQ 10 intervention studies in humans with a direct focus on markers of DNA damage are limited. Thus, more well-designed studies in healthy and disease populations with long-term follow up results are needed to substantiate the reported beneficial effects of CoQ 10 on prevention of DNA damage.

  17. Micronutrient special issue: Coenzyme Q{sub 10} requirements for DNA damage prevention

    Energy Technology Data Exchange (ETDEWEB)

    Schmelzer, Constance, E-mail: schmelzer@fbn-dummerstorf.de [Leibniz Institute for Farm Animal Biology (FBN), Nutritional Physiology, Wilhelm-Stahl-Allee 2, 18196 Dummerstorf (Germany); Doering, Frank [University of Kiel, Institute of Human Nutrition and Food Science, Molecular Prevention, Heinrich-Hecht-Platz 10, 24118 Kiel (Germany)

    2012-05-01

    Coenzyme Q{sub 10} (CoQ{sub 10}) is an essential component for electron transport in the mitochondrial respiratory chain and serves as cofactor in several biological processes. The reduced form of CoQ{sub 10} (ubiquinol, Q{sub 10}H{sub 2}) is an effective antioxidant in biological membranes. During the last years, particular interest has been grown on molecular effects of CoQ{sub 10} supplementation on mechanisms related to DNA damage prevention. This review describes recent advances in our understanding about the impact of CoQ{sub 10} on genomic stability in cells, animals and humans. With regard to several in vitro and in vivo studies, CoQ{sub 10} provides protective effects on several markers of oxidative DNA damage and genomic stability. In comparison to the number of studies reporting preventive effects of CoQ{sub 10} on oxidative stress biomarkers, CoQ{sub 10} intervention studies in humans with a direct focus on markers of DNA damage are limited. Thus, more well-designed studies in healthy and disease populations with long-term follow up results are needed to substantiate the reported beneficial effects of CoQ{sub 10} on prevention of DNA damage.

  18. Oxidative stress correlates with headache symptoms in fibromyalgia: coenzyme Q₁₀ effect on clinical improvement.

    Science.gov (United States)

    Cordero, Mario D; Cano-García, Francisco Javier; Alcocer-Gómez, Elísabet; De Miguel, Manuel; Sánchez-Alcázar, José Antonio

    2012-01-01

    Fibromyalgia (FM) is a chronic pain syndrome with unknown etiology and a wide spectrum of symptoms such as allodynia, debilitating fatigue, joint stiffness and migraine. Recent studies have shown some evidences demonstrating that oxidative stress is associated to clinical symptoms in FM of fibromyalgia. We examined oxidative stress and bioenergetic status in blood mononuclear cells (BMCs) and its association to headache symptoms in FM patients. The effects of oral coenzyme Q(10) (CoQ(10)) supplementation on biochemical markers and clinical improvement were also evaluated. We studied 20 FM patients and 15 healthy controls. Clinical parameters were evaluated using the Fibromyalgia Impact Questionnaire (FIQ), visual analogues scales (VAS), and the Headache Impact Test (HIT-6). Oxidative stress was determined by measuring CoQ(10), catalase and lipid peroxidation (LPO) levels in BMCs. Bioenergetic status was assessed by measuring ATP levels in BMCs. We found decreased CoQ(10), catalase and ATP levels in BMCs from FM patients as compared to normal control (P headache parameters were observed (r  = -0.59, P headache symptoms (P stress in the headache symptoms associated with FM. CoQ10 supplementation should be examined in a larger placebo controlled trial as a possible treatment in FM.

  19. Comparision of Inhibitory effects of Satureja Khozistanica,vitamin E and coenzyme Q10 on LDL peroxidation induced-CuSO4 in vitro

    Directory of Open Access Journals (Sweden)

    hasan Ahmadvand

    2010-02-01

    Full Text Available Oxidation of low-density lipoprotein (LDL has been strongly suggested as a key factor in the pathogenesis of atherosclerosis. Thus the inclusion of some anti-oxidant compounds such as Satureja Khozistanica,vitamin E and coenzyme Q10 in daily dietary food stuff may inhibit the production of oxidized LDL and may decrease both the development and the progression of atherosclerosis. The present study investigated the inhibitory effects of Satureja Khozistanica, vitamin E and coenzyme Q10 on LDL peroxidation induced by CuSO4 quantitatively in vitro. Materials and Methods: LDL was incubated with CuSO4 and the formation of conjugated dienes and thiobarbituric acid reactive substances (TBARS of LDL were monitored as markers of LDL oxidation. Inhibition of this Cu-induced oxidation was studied in the presence of extracts of Satureja Khozistanica,vitamin E and coenzyme Q10. Results: It was demonstrated that Satureja Khozistanica like vitamin E and coenzyme Q10 is able to inhibit LDL oxidation and decrease the resistance of LDL against oxidation in vitro. Conclusion: This study showed that Satureja Khozistanica similar to vitamin E and coenzyme Q10 prevented the oxidation of LDL in vitro and it may suggest that they have the similar effect in vivo

  20. LC/MS/MS analysis of α-tocopherol and coenzyme Q10 content in lyophilized royal jelly, beebread and drone homogenate.

    Science.gov (United States)

    Hryniewicka, Marta; Karpinska, Agnieszka; Kijewska, Marta; Turkowicz, Monika Joanna; Karpinska, Joanna

    2016-11-01

    This study shows the results of application liquid chromatography-tandem mass spectrometry (LC/MS/MS) for assay of the content of α-tocopherol and coenzyme Q 10 in bee products of animal origin, i.e. royal jelly, beebread and drone homogenate. The biological matrix was removed using extraction with n-hexane. It was found that drone homogenate is a rich source of coenzyme Q 10 . It contains only 8 ± 1 µg/g of α-tocopherol and 20 ± 2 µg/g of coenzyme Q 10 . The contents of assayed compounds in royal jelly were 16 ± 3 and 8 ± 0.2 µg/g of α-tocopherol and coenzyme Q 10 , respectively. Beebread appeared to be the richest of α-tocopherol. Its level was 80 ± 30 µg/g, while the level of coenzyme Q 10 was only 11.5 ± 0.3 µg/g. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Paraquat induces oxidative stress and neuronal cell death; neuroprotection by water-soluble Coenzyme Q10

    International Nuclear Information System (INIS)

    McCarthy, S.; Somayajulu, M.; Sikorska, M.; Borowy-Borowski, H.; Pandey, S.

    2004-01-01

    Neuronal cell death induced by oxidative stress is correlated with numerous neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. The causes of sporadic forms of age-related neurodegenerative diseases are still unknown. Recently, a correlation between paraquat exposure and neurodegenerative diseases has been observed. Paraquat, a nonselective herbicide, was once widely used in North America and is still routinely used in Taiwan. We have used differentiated Human Neuroblastoma (SHSY-5Y) cells as an in vitro model to study the mechanism of cell death induced by paraquat. We observed that paraquat-induced oxidative stress in differentiated SHSY-5Y cells as indicated by an increase in the production of cellular reactive oxygen species (ROS). Furthermore, apoptosis was evident as indicated by cellular and nuclear morphology and DNA fragmentation. Interestingly, pretreatment of SHSY-5Y cells with water-soluble Coenzyme Q 10 (CoQ 10 ) before paraquat exposure inhibited ROS generation. Pretreatment with CoQ 10 also significantly reduced the number of apoptotic cells and DNA fragmentation. We also analyzed the effect of paraquat and CoQ 10 on isolated mitochondria. Our results indicated that treatment with paraquat induced the generation of ROS from isolated mitochondria and depolarization of the inner mitochondrial membrane. Pretreatment with CoQ 10 was able to inhibit ROS generation from isolated mitochondria as well as the collapse of mitochondrial membrane potential. Our results indicate that water-soluble CoQ 10 can prevent oxidative stress and neuronal damage induced by paraquat and therefore, can be used for the prevention and therapy of neurodegenerative diseases caused by environmental toxins

  2. Oxidative Stress Correlates with Headache Symptoms in Fibromyalgia: Coenzyme Q10 Effect on Clinical Improvement

    Science.gov (United States)

    Cordero, Mario D.; Cano-García, Francisco Javier; Alcocer-Gómez, Elísabet; De Miguel, Manuel; Sánchez-Alcázar, José Antonio

    2012-01-01

    Background Fibromyalgia (FM) is a chronic pain syndrome with unknown etiology and a wide spectrum of symptoms such as allodynia, debilitating fatigue, joint stiffness and migraine. Recent studies have shown some evidences demonstrating that oxidative stress is associated to clinical symptoms in FM of fibromyalgia. We examined oxidative stress and bioenergetic status in blood mononuclear cells (BMCs) and its association to headache symptoms in FM patients. The effects of oral coenzyme Q10 (CoQ10) supplementation on biochemical markers and clinical improvement were also evaluated. Methods We studied 20 FM patients and 15 healthy controls. Clinical parameters were evaluated using the Fibromyalgia Impact Questionnaire (FIQ), visual analogues scales (VAS), and the Headache Impact Test (HIT-6). Oxidative stress was determined by measuring CoQ10, catalase and lipid peroxidation (LPO) levels in BMCs. Bioenergetic status was assessed by measuring ATP levels in BMCs. Results We found decreased CoQ10, catalase and ATP levels in BMCs from FM patients as compared to normal control (P<0.05 and P<0.001, respectively) We also found increased level of LPO in BMCs from FM patients as compared to normal control (P<0.001). Significant negative correlations between CoQ10 or catalase levels in BMCs and headache parameters were observed (r = −0.59, P<0.05; r = −0.68, P<0.05, respectively). Furthermore, LPO levels showed a significant positive correlation with HIT-6 (r = 0.33, P<0.05). Oral CoQ10 supplementation restored biochemical parameters and induced a significant improvement in clinical and headache symptoms (P<0.001). Discussion The results of this study suggest a role for mitochondrial dysfunction and oxidative stress in the headache symptoms associated with FM. CoQ10 supplementation should be examined in a larger placebo controlled trial as a possible treatment in FM. PMID:22532869

  3. Characterisation and Skin Distribution of Lecithin-Based Coenzyme Q10-Loaded Lipid Nanocapsules

    Science.gov (United States)

    Zhou, Huafeng; Yue, Yang; Liu, Guanlan; Li, Yan; Zhang, Jing; Yan, Zemin; Duan, Mingxing

    2010-10-01

    The purpose of this study was to investigate the influence of the inner lipid ratio on the physicochemical properties and skin targeting of surfactant-free lecithin-based coenzyme Q10-loaded lipid nanocapsules (CoQ10-LNCs). The smaller particle size of CoQ10-LNCs was achieved by high pressure and a lower ratio of CoQ10/GTCC (Caprylic/capric triglyceride); however, the zeta potential of CoQ10-LNCs was above /- 60 mV/ with no distinct difference among them at different ratios of CoQ10/GTCC. Both the crystallisation point and the index decreased with the decreasing ratio of CoQ10/GTCC and smaller particle size; interestingly, the supercooled state of CoQ10-LNCs was observed at particle size below about 200 nm, as verified by differential scanning calorimetry (DSC) in one heating-cooling cycle. The lecithin monolayer sphere structure of CoQ10-LNCs was investigated by cryogenic transmission electron microscopy (Cryo-TEM). The skin penetration results revealed that the distribution of Nile red-loaded CoQ10-LNCs depended on the ratio of inner CoQ10/GTCC; moreover, epidermal targeting and superficial dermal targeting were achieved by the CoQ10-LNCs application. The highest fluorescence response was observed at a ratio of inner CoQ10/GTCC of 1:1. These observations suggest that lecithin-based LNCs could be used as a promising topical delivery vehicle for lipophilic compounds.

  4. Dependence of mitochondrial coenzyme A uptake on the membrane electrical gradient

    International Nuclear Information System (INIS)

    Tahiliani, A.G.

    1989-01-01

    Coenzyme A (CoA) transport was studied in isolated rat heart mitochondria. Uptake of CoA was assayed by determining [3H]CoA associated with mitochondria under various conditions. Various oxidizable substrates including alpha-ketoglutarate, succinate, or malate stimulated CoA uptake. The membrane proton (delta pH) and electrical (delta psi) gradients, which dissipated with time in the absence of substrate, were maintained at their initial levels throughout the incubation in the presence of substrate. Addition of phosphate caused a concentration-dependent decrease of both delta pH and CoA uptake. Nigericin also dissipated the proton gradient and prevented CoA uptake. Valinomycin also prevented CoA uptake into mitochondria. Although the proton gradient was unaffected, the electrical gradient was completely abolished in the presence of valinomycin. Addition of 5 mM phosphate 10 min after the start of incubation prevented further uptake of CoA into mitochondria. A rapid dissipation of the proton gradient upon addition of phosphate was observed. Addition of nigericin or valinomycin 10 min after the start of incubation also resulted in no further uptake of CoA into with mitochondria; valinomycin caused an apparent efflux of CoA from mitochondria. Uptake was found to be sensitive to external pH displaying a pH optimum at pHext 8.0. Although nigericin significantly inhibited CoA uptake over the pHext range of 6.75-8, maximal transport was observed around pHext 8.0-8.25. Valinomycin, on the other hand, abolished transport over the entire pH range. The results suggest that mitochondrial CoA transport is determined by the membrane electrical gradient. The apparent dependence of CoA uptake on an intact membrane pH gradient is probably the result of modulation of CoA transport by matrix pH

  5. Evidence against translational repression by the carboxyltransferase component of Escherichia coli acetyl coenzyme A carboxylase.

    Science.gov (United States)

    Smith, Alexander C; Cronan, John E

    2014-11-01

    In Escherichia coli, synthesis of the malonyl coenzyme A (malonyl-CoA) required for membrane lipid synthesis is catalyzed by acetyl-CoA carboxylase, a large complex composed of four subunits. The subunit proteins are needed in a defined stoichiometry, and it remains unclear how such production is achieved since the proteins are encoded at three different loci. Meades and coworkers (G. Meades, Jr., B. K. Benson, A. Grove, and G. L. Waldrop, Nucleic Acids Res. 38:1217-1227, 2010, doi:http://dx.doi.org/10.1093/nar/gkp1079) reported that coordinated production of the AccA and AccD subunits is due to a translational repression mechanism exerted by the proteins themselves. The AccA and AccD subunits form the carboxyltransferase (CT) heterotetramer that catalyzes the second partial reaction of acetyl-CoA carboxylase. Meades et al. reported that CT tetramers bind the central portions of the accA and accD mRNAs and block their translation in vitro. However, long mRNA molecules (500 to 600 bases) were required for CT binding, but such long mRNA molecules devoid of ribosomes seemed unlikely to exist in vivo. This, plus problematical aspects of the data reported by Meades and coworkers, led us to perform in vivo experiments to test CT tetramer-mediated translational repression of the accA and accD mRNAs. We report that increased levels of CT tetramer have no detectable effect on translation of the CT subunit mRNAs. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  6. Inhibition of Coenzyme Qs Accumulation in Engineered Escherichia coli by High Concentration of Farnesyl Diphosphate

    Science.gov (United States)

    Samoudi, Mojtaba; Omid Yeganeh, Negar; Shahbani Zahiri, Hossein; Shariati, Parvin; Hajhosseini, Reza

    2015-01-01

    Background: Coenzyme Q 10 (CoQ 10 ) is an isoprenoid component used widely in nutraceutical industries. Farnesyl diphosphate synthase (FPPS) is a responsible enzyme for biosynthesis of farnesyl diphosphate (FPP), a key precursor for CoQs production. This research involved investigating the effect of FPPS over-expression on CoQs production in engineered CoQ 10 -producing Escherichia coli (E. coli). Methods: Two CoQ 10 -producing strains, as referred to E. coli Ba and E. coli Br, were transformed by the encoding gene for FPPS (ispA) under the control of either the trc or P BAD promoters. Results: Over-expression of ispA under the control of P BAD promoter led to a relative increase in CoQ 10 production only in recombinant E. coli Br although induction by arabinose resulted in partial reduction of CoQ 10 production in both recombinant E. coli Ba and E. coli Br strains. Over-expression of ispA under the control of stronger trc promoter, however, led to a severe decrease in CoQ 10 production in both recombinant E. coli Ba and E. coli Br strains, as reflected by reductions from 629±40 to 30±13 and 564±28 to 80±14 μg/g Dried Cell Weight (DCW), respectively. The results showed high level of FPP reduces endogenous CoQ 8 production as well and that CoQs are produced in a complimentary manner, as the increase in production of one decreases the production of the other. Conclusion: The reduction in CoQ 10 production can be a result of Dds inhibition by high FPP concentration. Therefore, more effort is needed to verify the role of intermediate metabolite concentration and to optimize production of CoQ 10 . PMID:26306151

  7. Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and cholesterol biosynthesis by oxylanosterols

    Energy Technology Data Exchange (ETDEWEB)

    Panini, S.R.; Sexton, R.C.; Gupta, A.K.; Parish, E.J.; Chitrakorn, S.; Rudney, H.

    1986-11-01

    Treatment of rat intestinal epithelial cell cultures with the oxidosqualene cyclase inhibitor, 3 beta-(2-(diethylamino)-ethoxy)androst-5-en-17-one (U18666A), resulted in an accumulation of squalene 2,3:22,23-dioxide (SDO). When U18666A was withdrawn and the cells were treated with the sterol 14 alpha-demethylase inhibitor, ketoconazole, SDO was metabolized to a product identified as 24(S),25-epoxylanosterol. To test the biological effects and cellular metabolism of this compound, we prepared 24(RS),25-epoxylanosterol by chemical synthesis. The epimeric mixture of 24,25-epoxylanosterols could be resolved by high performance liquid chromatography on a wide-pore, non-endcapped, reverse phase column. Both epimers were effective suppressors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity of IEC-6 cells. The suppressive action of the natural epimer, 24(S),25-epoxylanosterol, but not that of 24(R),25-epoxylanosterol could be completely prevented by ketoconazole. IEC-6 cells could efficiently metabolize biosynthetic 24(S),25-epoxy(/sup 3/H)anosterol mainly to the known reductase-suppressor 24(S),25-epoxycholesterol. This metabolism was substantially reduced by ketoconazole. These data support the conclusion that 24(S),25-epoxylanosterol per se is not a suppressor of HMG-CoA reductase activity but is a precursor to a regulatory oxysterol(s). It has recently been reported that 25-hydroxycholesterol can occur naturally in cultured cells in amounts sufficient to effect regulation of HMG-CoA reductase. In order to investigate the biological effects of possible precursors of 25-hydroxycholesterol, we chemically synthesized 25-hydroxylanosterol and 25-hydroxylanostene-3-one. Both oxylanosterol derivatives suppressed cellular sterol synthesis at the level of HMG-CoA reductase. (Abstract Truncated)

  8. Inhibitors of hydroxymethylglutaryl-coenzyme A reductase and risk of fracture among older women.

    Science.gov (United States)

    Chan, K A; Andrade, S E; Boles, M; Buist, D S; Chase, G A; Donahue, J G; Goodman, M J; Gurwitz, J H; LaCroix, A Z; Platt, R

    2000-06-24

    Inhibitors of hydroxymethylglutaryl-coenzyme A reductase (statins) increase new bone formation in rodents and in human cells in vitro. Statin use is associated with increased bone mineral density of the femoral neck. We undertook a population-based case-control study at six health-maintenance organisations in the USA to investigate further the relation between statin use and fracture risk among older women. We investigated women aged 60 years or older. Exposure, outcome, and confounder information was obtained from automated claims and pharmacy data from October, 1994, to September, 1997. Cases had an incident diagnosis of non-pathological fracture of the hip, humerus, distal tibia, wrist, or vertebrae between October, 1996, and September, 1997. Controls had no fracture during this period. We excluded women with records of dispensing of drugs to treat osteoporosis. There were 928 cases and 2747 controls. Compared with women who had no record of statin dispensing during the previous 2 years, women with 13 or more statin dispensings during this period had a decreased risk of non-pathological fracture (odds ratio 0.48 [95% CI 0.27-0.83]) after adjustment for age, number of hospital admissions during the previous year, chronic disease score, and use of non-statin lipid-lowering drugs. No association was found between fracture risk and fewer than 13 dispensings of statins or between fracture risk and use of non-statin lipid-lowering drugs. Statins seem to be protective against non-pathological fracture among older women. These findings are compatible with the hypothesis that statins increase bone mineral density in human beings and thereby decrease the risk of osteoporotic fractures.

  9. Functional characterization of human COQ4, a gene required for Coenzyme Q10 biosynthesis

    International Nuclear Information System (INIS)

    Casarin, Alberto; Jimenez-Ortega, Jose Carlos; Trevisson, Eva; Pertegato, Vanessa; Doimo, Mara; Ferrero-Gomez, Maria Lara; Abbadi, Sara; Artuch, Rafael; Quinzii, Catarina; Hirano, Michio; Basso, Giuseppe; Ocana, Carlos Santos; Navas, Placido; Salviati, Leonardo

    2008-01-01

    Defects in genes involved in coenzyme Q (CoQ) biosynthesis cause primary CoQ deficiency, a severe multisystem disorders presenting as progressive encephalomyopathy and nephropathy. The COQ4 gene encodes an essential factor for biosynthesis in Saccharomyces cerevisiae. We have identified and cloned its human ortholog, COQ4, which is located on chromosome 9q34.13, and is transcribed into a 795 base-pair open reading frame, encoding a 265 amino acid (aa) protein (Isoform 1) with a predicted N-terminal mitochondrial targeting sequence. It shares 39% identity and 55% similarity with the yeast protein. Coq4 protein has no known enzymatic function, but may be a core component of multisubunit complex required for CoQ biosynthesis. The human transcript is detected in Northern blots as a ∼1.4 kb single band and is expressed ubiquitously, but at high levels in liver, lung, and pancreas. Transcription initiates at multiple sites, located 333-23 nucleotides upstream of the ATG. A second group of transcripts originating inside intron 1 of the gene encodes a 241 aa protein, which lacks the mitochondrial targeting sequence (isoform 2). Expression of GFP-fusion proteins in HeLa cells confirmed that only isoform 1 is targeted to mitochondria. The functional significance of the second isoform is unknown. Human COQ4 isoform 1, expressed from a multicopy plasmid, efficiently restores both growth in glycerol, and CoQ content in COQ4 null yeast strains. Human COQ4 is an interesting candidate gene for patients with isolated CoQ 10 deficiency

  10. Decreased hepatic contents of coenzyme A molecular species in mice after subchronic mild social defeat stress.

    Science.gov (United States)

    Kubota, Yoshifumi; Goto, Tatsuhiko; Hagiya, Yuki; Chohnan, Shigeru; Toyoda, Atsushi

    2016-01-01

    Social stress may precipitate psychiatric disorders such as depression, which is related to the occurrence of the metabolic syndrome, including obesity and type 2 diabetes. We have evaluated the effects of social stress on central and peripheral metabolism using a model of depression in mice. In the present study, we focused on coenzyme A (CoA) molecular species [i.e. non-esterified CoA (CoASH), acetyl-CoA and malonyl-CoA] which play important roles in numerous metabolic pathways, and we analyzed changes in expression of these molecules in the hypothalamus and liver of adult male mice (C57BL/6J) subjected to 10 days of subchronic mild social defeat stress (sCSDS) with ICR mice as aggressors. Mice (n = 12) exposed to showed hyperphagia- and polydipsia-like symptoms and increased body weight gain compared with control mice which were not affected by exposure to ICR mice (n = 12). To elucidate the underlying metabolic features in the sCSDS model, acetyl-CoA, malonyl-CoA and CoASH tissue levels were analyzed using the acyl-CoA cycling method. The levels of hypothalamic malonyl-CoA, which decreases feeding behavior, were not influenced by sCSDS. However, sCSDS reduced levels of acetyl-CoA, malonyl-CoA and total CoA (sum of the three CoA molecular species) in the liver. Hence, hyperphagia-like symptoms in sCSDS mice evidently occurred independently of hypothalamic malonyl-CoA, but might consequently lead to down-regulation of hepatic CoA via altered expression of nudix hydrolase 7. Future studies should investigate the molecular mechanism(s) underlying the down-regulation of liver CoA pools in sCSDS mice.

  11. Treatment of cyclic vomiting syndrome with co-enzyme Q10 and amitriptyline, a retrospective study

    Directory of Open Access Journals (Sweden)

    Preston Amy

    2010-01-01

    Full Text Available Abstract Background Cyclic vomiting syndrome (CVS, which is defined by recurrent stereotypical episodes of nausea and vomiting, is a relatively-common disabling condition that is associated with migraine headache and mitochondrial dysfunction. Co-enzyme Q10 (Co-Q is a nutritional supplement that has demonstrated efficacy in pediatric and adult migraine. It is increasingly used in CVS despite the complete lack of studies to demonstrate its value in treatment Methods Using an Internet-based survey filled out by subjects with CVS or their parents, the efficacy, tolerability and subject satisfaction in CVS prophylaxis were queried. Subjects taking Co-Q (22 subjects were compared against those taking amitriptyline (162 subjects, which is the general standard-of-care. Results Subjects/parents reported similar levels of efficacy for a variety of episode parameters (frequency, duration, number of emesis, nausea severity. There was a 50% reduction in at least one of those four parameters in 72% of subjects treated with amitriptyline and 68% of subjects treated Co-Q. However, while no side effects were reported on Co-Q, 50% of subjects on amitriptyline reported side effects (P = 5 × 10-7, resulting in 21% discontinuing treatment (P = 0.007. Subjects/parents considered the benefits to outweigh the risks of treatment in 47% of cases on amitriptyline and 77% of cases on Co-Q (P = 0.008. Conclusion Our data suggest that the natural food supplement Co-Q is potentially efficacious and tolerable in the treatment of CVS, and should be considered as an option in CVS prophylaxis. Our data would likely be helpful in the design of a double-blind clinical trial.

  12. Cold-Induced Ascites in Broilers: Effects of Vitamin C and Coenzyme Q10

    Directory of Open Access Journals (Sweden)

    MH Nemati

    Full Text Available ABSTRACT We hypothesized that the supplementation of vitamin C (Vit. C and coenzyme Q10 (CoQ10 alone or in combination could reduce the negative effects of cold stress in broilers. Four hundred male chicks were exposed for 24 h to cold stress (15 ºC starting from 15d of age, while a positive control group (PC, 100 birds was kept under normal temperature condition. The experimental groups under cold stress (four treatments in 5 replicates of 20 birds were: negative control (NC, basal diet, Vit. C (basal diet + 300 mg/kg Vit. C, CoQ10 (basal diet + 40 mg/kg CoQ10 and Vit. C plus CoQ10 (basal diet + Vit. C+ CoQ10at above mentioned doses. Vit. C or CoQ10 supplementation were restored (p<0.01 performance and lowered (p<0.01 ascites mortality. Blood hematocrit and hemoglobin concentration were decreased (p<0.01 to the level comparable to PC by Vit. C supplementation. Lower plasma concentrations of thyroxin (T4 and higher triiodothyronine (T3 were observed in NC birds (p<0.01 and were not affected by Vit. C or CoQ10. In conclusion, supplementation of Vit. C or CoQ10 in diet of broilers under cold stress conditions resulted improved performance parameters (body weight and feed conversion ratio and ascites related traits (low red blood cell count, hematocrit, T3, and heart weights and high T4. No additional benefit was observed by combination of Vit. C and CoQ10.

  13. Border between natural product and drug: Comparison of the related benzoquinones idebenone and coenzyme Q10

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    Nuri Gueven

    2015-04-01

    Full Text Available Coenzyme Q10 is a ubiquitous component of cellular membranes and belongs to the class of benzoquinones that mainly differ with regards to the length and composition of their hydrophobic tail. The characteristic quinone group can accept electrons from various biological sources and is converted by a one electron transfer to the unstable semiquinone or by a two electron transfer to the more stable hydroquinone. This feature makes CoQ10 the bona fide cellular electron transfer molecule within the mitochondrial respiratory chain and also makes it a potent cellular antioxidant. These activities serve as justification for its popular use as food supplement. Another quinone with similarities to the naturally occurring CoQ10 is idebenone, which shares its quinone moiety with CoQ10, but at the same time differs from CoQ10 by the presence of a much shorter, less lipophilic tail. However, despite its similarity to CoQ10, idebenone cannot be isolated from any natural sources but instead was synthesized and selected as a pharmacologically active compound in the 1980s by Takeda Pharmaceuticals purely based on its pharmacological properties. Several recent clinical trials demonstrated some therapeutic efficacy of idebenone in different indications and as a consequence, many practitioners question if the freely available CoQ10 could not be used instead. Here, we describe the molecular and pharmacological features of both molecules that arise from their structural differences to answer the question if idebenone is merely a CoQ10 analogue as frequently perpetuated in the literature or a pharmaceutical drug with entirely different features.

  14. Novel Lipid-Free Nanoformulation for Improving Oral Bioavailability of Coenzyme Q10

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    Huafeng Zhou

    2014-01-01

    Full Text Available To improve the bioavailability of orally administered lipophilic coenzyme Q10 (CoQ10, we formulated a novel lipid-free nano-CoQ10 system stabilized by various surfactants. Nano-CoQ10s, composed of 2.5% (w/w CoQ10, 1.67% (w/w surfactant, and 41.67% (w/w glycerol, were prepared by hot high-pressure homogenization. The resulting formulations were characterized by particle size, zeta potential, differential scanning calorimetry, and cryogenic transmission electron microscopy. We found that the mean particle size of all nano-CoQ10s ranged from 66.3±1.5 nm to 92.7±1.5 nm and the zeta potential ranged from -12.8±1.4 mV to -41.6±1.4 mV. The CoQ10 in nano-CoQ10s likely existed in a supercooled state, and nano-CoQ10s stored in a brown sealed bottle were stable for 180 days at 25°C. The bioavailability of CoQ10 was evaluated following oral administration of CoQ10 formulations in Sprague-Dawley rats. Compared to the values observed following administration of CoQ10-Suspension, nano-CoQ10 modified with various surfactants significantly increased the maximum plasma concentration and the area under the plasma concentration-time curve. Thus, the lipid-free system of a nano-CoQ10 stabilized with a surfactant may be an effective vehicle for improving oral bioavailability of CoQ10.

  15. Functional conservation of coenzyme Q biosynthetic genes among yeasts, plants, and humans.

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    Kazuhiro Hayashi

    Full Text Available Coenzyme Q (CoQ is an essential factor for aerobic growth and oxidative phosphorylation in the electron transport system. The biosynthetic pathway for CoQ has been proposed mainly from biochemical and genetic analyses of Escherichia coli and Saccharomyces cerevisiae; however, the biosynthetic pathway in higher eukaryotes has been explored in only a limited number of studies. We previously reported the roles of several genes involved in CoQ synthesis in the fission yeast Schizosaccharomyces pombe. Here, we expand these findings by identifying ten genes (dps1, dlp1, ppt1, and coq3-9 that are required for CoQ synthesis. CoQ10-deficient S. pombe coq deletion strains were generated and characterized. All mutant fission yeast strains were sensitive to oxidative stress, produced a large amount of sulfide, required an antioxidant to grow on minimal medium, and did not survive at the stationary phase. To compare the biosynthetic pathway of CoQ in fission yeast with that in higher eukaryotes, the ability of CoQ biosynthetic genes from humans and plants (Arabidopsis thaliana to functionally complement the S. pombe coq deletion strains was determined. With the exception of COQ9, expression of all other human and plant COQ genes recovered CoQ10 production by the fission yeast coq deletion strains, although the addition of a mitochondrial targeting sequence was required for human COQ3 and COQ7, as well as A. thaliana COQ6. In summary, this study describes the functional conservation of CoQ biosynthetic genes between yeasts, humans, and plants.

  16. Effects of Coenzyme Q10 on Markers of Inflammation: A Systematic Review and Meta-Analysis.

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    Junya Zhai

    Full Text Available Chronic inflammation contributes to the onset and development of metabolic diseases. Clinical evidence has suggested that coenzyme Q10 (CoQ10 has some effects on inflammatory markers. However, these results are equivocal. The aim of this systematic review was to assess the effects of CoQ10 on serum levels of inflammatory markers in people with metabolic diseases.Electronic databases were searched up to February 2016 for randomized controlled trials (RCTs. The outcome parameters were related to inflammatory factors, including interleukin-6 (IL-6, tumor necrosis factor-alpha (TNF-α and C reactive protein (CRP. RevMan software was used for meta-analysis. Meta-regression analysis, Egger line regression test and Begg rank correlation test were performed by STATA software.Nine trials involving 428 subjects were included in this meta-analysis. The results showed that compared with control group, CoQ10 supplementation has significantly improved the serum level of CoQ10 by 1.17μg/ml [MD = 1.17, 95% CI (0.47 to 1.87 μg/ml, I2 = 94%]. Meanwhile, it has significantly decreased TNF-α by 0.45 pg/ml [MD = -0.45, 95% CI (-0.67 to -0.24 pg/ml, I2 = 0%]. No significant difference was observed between CoQ10 and placebo with regard to CRP [MD = -0.21, 95% CI (-0.60 to 0.17 mg/L, I2 = 21%] and IL-6 [MD = -0.89, 95% CI (-1.95 to 0.16 pg/ml, I2 = 84%].CoQ10 supplementation may partly improve the process of inflammatory state. The effects of CoQ10 on inflammation should be further investigated by conducting larger sample size and well-defined trials of long enough duration.

  17. Primary coenzyme Q deficiency in Pdss2 mutant mice causes isolated renal disease.

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    Min Peng

    2008-04-01

    Full Text Available Coenzyme Q (CoQ is an essential electron carrier in the respiratory chain whose deficiency has been implicated in a wide variety of human mitochondrial disease manifestations. Its multi-step biosynthesis involves production of polyisoprenoid diphosphate in a reaction that requires the enzymes be encoded by PDSS1 and PDSS2. Homozygous mutations in either of these genes, in humans, lead to severe neuromuscular disease, with nephrotic syndrome seen in PDSS2 deficiency. We now show that a presumed autoimmune kidney disease in mice with the missense Pdss2(kd/kd genotype can be attributed to a mitochondrial CoQ biosynthetic defect. Levels of CoQ9 and CoQ10 in kidney homogenates from B6.Pdss2(kd/kd mutants were significantly lower than those in B6 control mice. Disease manifestations originate specifically in glomerular podocytes, as renal disease is seen in Podocin/cre,Pdss2(loxP/loxP knockout mice but not in conditional knockouts targeted to renal tubular epithelium, monocytes, or hepatocytes. Liver-conditional B6.Alb/cre,Pdss2(loxP/loxP knockout mice have no overt disease despite demonstration that their livers have undetectable CoQ9 levels, impaired respiratory capacity, and significantly altered intermediary metabolism as evidenced by transcriptional profiling and amino acid quantitation. These data suggest that disease manifestations of CoQ deficiency relate to tissue-specific respiratory capacity thresholds, with glomerular podocytes displaying the greatest sensitivity to Pdss2 impairment.

  18. Coenzyme Q10 Status as a Determinant of Muscular Strength in Two Independent Cohorts.

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    Alexandra Fischer

    Full Text Available Aging is associated with sarcopenia, which is a loss of skeletal muscle mass and function. Coenzyme Q10 (CoQ10 is involved in several important functions that are related to bioenergetics and protection against oxidative damage; however, the role of CoQ10 as a determinant of muscular strength is not well documented. The aim of the present study was to evaluate the determinants of muscular strength by examining hand grip force in relation to CoQ10 status, gender, age and body mass index (BMI in two independent cohorts (n = 334, n = 967. Furthermore, peak flow as a function of respiratory muscle force was assessed. Spearman's correlation revealed a significant positive association between CoQ10/cholesterol level and hand grip in the basic study population (p<0.01 as well as in the validation population (p<0.001. In the latter, we also found a negative correlation with the CoQ10 redox state (p<0.01, which represents a lower percentage of the reduced form of CoQ10 (ubiquinol in subjects who exhibit a lower muscular strength. Furthermore, the age of the subjects showed a negative correlation with hand grip (p<0.001, whereas BMI was positively correlated with hand grip (p<0.01, although only in the normal weight subgroup (BMI <25 kg/m2. Analysis of the covariance (ANCOVA with hand grip as the dependent variable revealed CoQ10/cholesterol as a determinant of muscular strength and gender as the strongest effector of hand grip. In conclusion, our data suggest that both a low CoQ10/cholesterol level and a low percentage of the reduced form of CoQ10 could be an indicator of an increased risk of sarcopenia in humans due to their negative associations to upper body muscle strength, peak flow and muscle mass.

  19. Characterisation and Skin Distribution of Lecithin-Based Coenzyme Q10-Loaded Lipid Nanocapsules

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    Yan Zemin

    2010-01-01

    Full Text Available Abstract The purpose of this study was to investigate the influence of the inner lipid ratio on the physicochemical properties and skin targeting of surfactant-free lecithin-based coenzyme Q10-loaded lipid nanocapsules (CoQ10-LNCs. The smaller particle size of CoQ10-LNCs was achieved by high pressure and a lower ratio of CoQ10/GTCC (Caprylic/capric triglyceride; however, the zeta potential of CoQ10-LNCs was above /− 60 mV/ with no distinct difference among them at different ratios of CoQ10/GTCC. Both the crystallisation point and the index decreased with the decreasing ratio of CoQ10/GTCC and smaller particle size; interestingly, the supercooled state of CoQ10-LNCs was observed at particle size below about 200 nm, as verified by differential scanning calorimetry (DSC in one heating–cooling cycle. The lecithin monolayer sphere structure of CoQ10-LNCs was investigated by cryogenic transmission electron microscopy (Cryo-TEM. The skin penetration results revealed that the distribution of Nile red-loaded CoQ10-LNCs depended on the ratio of inner CoQ10/GTCC; moreover, epidermal targeting and superficial dermal targeting were achieved by the CoQ10-LNCs application. The highest fluorescence response was observed at a ratio of inner CoQ10/GTCC of 1:1. These observations suggest that lecithin-based LNCs could be used as a promising topical delivery vehicle for lipophilic compounds.

  20. Coenzyme Q10 protects retinal cells from apoptosis induced by radiation in vitro and in vivo

    International Nuclear Information System (INIS)

    Lulli, M.; Witort, E.; Papucci, L.; Torre, E.; Schiavone, N.; Capaccioli, S.; Dal Monte, M.

    2012-01-01

    The key pathogenetic event of many retinopathies is apoptosis of retinal cells. Our previous studies have demonstrated that Coenzyme Q10 (CoQ10) prevents apoptosis of corneal keratocytes both in vitro and in vivo, by virtue of its ability to inhibit mitochondrial depolarization, independently of its free radical scavenger role. The aim of this study was to evaluate whether CoQ10 can protect cultured retinal cells and the retinas of rats from radiation-induced apoptosis, if instilled as eye drops in the cornea. In vitro experiments were carried out on cultured ARPE-19 or retinal ganglion cells (RGC)-5 cells pretreated with CoQ10 before eliciting apoptosis by ultraviolet (UV)- and γ-radiation, chemical hypoxia (Antimycin A) and serum starvation. Cell viability was evaluated by light microscopy and fluorescence activated cell sorting analysis. Apoptotic events were scored by time-lapse videomicroscopy. Mitochondrial permeability transition was evaluated by JC-1. The anti-apoptotic effectiveness of CoQ10 in retina was also evaluated by an in situ end-labeling assay in Wistar albino rats treated with CoQ10 eye drops prior to UV irradiation of the eye. CoQ10 substantially increased cell viability and lowered retinal cell apoptosis in response both to UV- and γ-radiation and to chemical hypoxia or serum starvation by inhibiting mitochondrion depolarization. In the rat, CoQ10, even when applied as eye drops on the cornea, protected all retina layers from ultraviolet radiation (UVR)-induced apoptosis. The ability of CoQ10 to protect retinal cells from radiation-induced apoptosis following its instillation on the cornea suggests the possibility for CoQ10 eye drops to become a future therapeutic countermeasure for radiation-induced retinal lesions. (author)

  1. Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and cholesterol biosynthesis by oxylanosterols

    International Nuclear Information System (INIS)

    Panini, S.R.; Sexton, R.C.; Gupta, A.K.; Parish, E.J.; Chitrakorn, S.; Rudney, H.

    1986-01-01

    Treatment of rat intestinal epithelial cell cultures with the oxidosqualene cyclase inhibitor, 3 beta-[2-(diethylamino)-ethoxy]androst-5-en-17-one (U18666A), resulted in an accumulation of squalene 2,3:22,23-dioxide (SDO). When U18666A was withdrawn and the cells were treated with the sterol 14 alpha-demethylase inhibitor, ketoconazole, SDO was metabolized to a product identified as 24(S),25-epoxylanosterol. To test the biological effects and cellular metabolism of this compound, we prepared 24(RS),25-epoxylanosterol by chemical synthesis. The epimeric mixture of 24,25-epoxylanosterols could be resolved by high performance liquid chromatography on a wide-pore, non-endcapped, reverse phase column. Both epimers were effective suppressors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity of IEC-6 cells. The suppressive action of the natural epimer, 24(S),25-epoxylanosterol, but not that of 24(R),25-epoxylanosterol could be completely prevented by ketoconazole. IEC-6 cells could efficiently metabolize biosynthetic 24(S),25-epoxy[ 3 H]anosterol mainly to the known reductase-suppressor 24(S),25-epoxycholesterol. This metabolism was substantially reduced by ketoconazole. These data support the conclusion that 24(S),25-epoxylanosterol per se is not a suppressor of HMG-CoA reductase activity but is a precursor to a regulatory oxysterol(s). It has recently been reported that 25-hydroxycholesterol can occur naturally in cultured cells in amounts sufficient to effect regulation of HMG-CoA reductase. In order to investigate the biological effects of possible precursors of 25-hydroxycholesterol, we chemically synthesized 25-hydroxylanosterol and 25-hydroxylanostene-3-one. Both oxylanosterol derivatives suppressed cellular sterol synthesis at the level of HMG-CoA reductase. (Abstract Truncated)

  2. Effects of benfotiamine and coenzyme Q10 on kidney damage induced gentamicin.

    Science.gov (United States)

    Ustuner, Mehmet Alperen; Kaman, Dilara; Colakoglu, Neriman

    2017-12-01

    Gentamicin (GM) is an effective antibiotic against severe infection but has limitations related to nephrotoxicity. In this study, we investigated whether benfotiamine (BFT) and coenzyme Q10 (CoQ10), could ameliorate the nephrotoxic effect of GM in rats. Rats were divided into five groups. Group 1 and 2 served as control and sham respectively, Group 3 as GM group, Group 4 as GM+CoQ10 and Group 5 as GM+BFT for 8days. At the end of the study, all rats were euthanized by cervical decapitation and then blood samples and kidneys were collected for further analysis. Serum urea, creatinine, cytokine TNF-a, oxidant and antioxidant parameters, as well as histopathological examination of kidney tissues were assessed. Gentamicin administration caused a severe nephrotoxicity which was evidenced by an elevated serum creatinine, urea and KIM-1 level as compared with the controls. Moreover, a significant increase in serum malondialdehyde, reduced glutathione. Histopathological examination of renal tissue in gentamisin administered group, there were extremly pronounced necrotic tubules in the renal cortex and hyalen cast accumulation in the medullar tubuli. BFT given to GM rats reduced these nephrotoxicity parameters. Serum creatinine, urea, and KIM-1 were almost normalized in the GM+BFT group. Benfotiamin treatment was significantly decreased necrotic tubuli and hyalen deposition in gentamisin plus benfotiamin group. CoQ10 given to GM rats did not cause any statistically significant alterations in these nephrotoxicity parameters when compared with GM group but histopathological examination of renal tissue in GM+CoQ10 administered group, CoQ10 treatment was decreased necrotic tubuli rate and hyalen accumulation in tubuli. The results from our study indicate that BFT supplement attenuates gentamicin-induced renal injury via the amelioration of oxidative stress and inflammation of renal tubular cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Oxidative stress correlates with headache symptoms in fibromyalgia: coenzyme Q₁₀ effect on clinical improvement.

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    Mario D Cordero

    Full Text Available BACKGROUND: Fibromyalgia (FM is a chronic pain syndrome with unknown etiology and a wide spectrum of symptoms such as allodynia, debilitating fatigue, joint stiffness and migraine. Recent studies have shown some evidences demonstrating that oxidative stress is associated to clinical symptoms in FM of fibromyalgia. We examined oxidative stress and bioenergetic status in blood mononuclear cells (BMCs and its association to headache symptoms in FM patients. The effects of oral coenzyme Q(10 (CoQ(10 supplementation on biochemical markers and clinical improvement were also evaluated. METHODS: We studied 20 FM patients and 15 healthy controls. Clinical parameters were evaluated using the Fibromyalgia Impact Questionnaire (FIQ, visual analogues scales (VAS, and the Headache Impact Test (HIT-6. Oxidative stress was determined by measuring CoQ(10, catalase and lipid peroxidation (LPO levels in BMCs. Bioenergetic status was assessed by measuring ATP levels in BMCs. RESULTS: We found decreased CoQ(10, catalase and ATP levels in BMCs from FM patients as compared to normal control (P < 0.05 and P < 0.001, respectively We also found increased level of LPO in BMCs from FM patients as compared to normal control (P < 0.001. Significant negative correlations between CoQ(10 or catalase levels in BMCs and headache parameters were observed (r  = -0.59, P < 0.05; r  =  -0.68, P < 0.05, respectively. Furthermore, LPO levels showed a significant positive correlation with HIT-6 (r = 0.33, P<0.05. Oral CoQ(10 supplementation restored biochemical parameters and induced a significant improvement in clinical and headache symptoms (P < 0.001. DISCUSSION: The results of this study suggest a role for mitochondrial dysfunction and oxidative stress in the headache symptoms associated with FM. CoQ10 supplementation should be examined in a larger placebo controlled trial as a possible treatment in FM.

  4. Arg279 is the key regulator of coenzyme selectivity in the flavin-dependent ornithine monooxygenase SidA.

    Science.gov (United States)

    Robinson, Reeder; Franceschini, Stefano; Fedkenheuer, Michael; Rodriguez, Pedro J; Ellerbrock, Jacob; Romero, Elvira; Echandi, Maria Paulina; Martin Del Campo, Julia S; Sobrado, Pablo

    2014-04-01

    Siderophore A (SidA) is a flavin-dependent monooxygenase that catalyzes the NAD(P)H- and oxygen-dependent hydroxylation of ornithine in the biosynthesis of siderophores in Aspergillus fumigatus and is essential for virulence. SidA can utilize both NADPH or NADH for activity; however, the enzyme is selective for NADPH. Structural analysis shows that R279 interacts with the 2'-phosphate of NADPH. To probe the role of electrostatic interactions in coenzyme selectivity, R279 was mutated to both an alanine and a glutamate. The mutant proteins were active but highly uncoupled, oxidizing NADPH and producing hydrogen peroxide instead of hydroxylated ornithine. For wtSidA, the catalytic efficiency was 6-fold higher with NADPH as compared to NADH. For the R279A mutant the catalytic efficiency was the same with both coenyzmes, while for the R279E mutant the catalytic efficiency was 5-fold higher with NADH. The effects are mainly due to an increase in the KD values, as no major changes on the kcat or flavin reduction values were observed. Thus, the absence of a positive charge leads to no coenzyme selectivity while introduction of a negative charge leads to preference for NADH. Flavin fluorescence studies suggest altered interaction between the flavin and NADP⁺ in the mutant enzymes. The effects are caused by different binding modes of the coenzyme upon removal of the positive charge at position 279, as no major conformational changes were observed in the structure for R279A. The results indicate that the positive charge at position 279 is critical for tight binding of NADPH and efficient hydroxylation. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Level of coenzyme A and the activity of certain dehydrogenases under chronic low dose X-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Cherkasova, L A; Novik, V A; Tsychun, G F [AN Belorusskoj SSR, Minsk. Inst. Fiziologii

    1975-01-01

    A study was made of the effect of long-term x ray irradiation (cumulative dose 50 R) on: the content of co-enzyme A (KoA) in the brain and liver, the activity of a number of oxydizing reducing enzymes in the brain mitochondria and heart muscle, and the blood glucocorticoid content. It was established that the metabolism of brain and liver KoA is quite stable, the enzymes of the brain tricarbonic acids and pyruvate-dehydrogenase cycle are labile.

  6. In vitro effects of zinc, D-aspartic acid, and coenzyme-Q10 on sperm function.

    Science.gov (United States)

    Giacone, Filippo; Condorelli, Rosita A; Mongioì, Laura M; Bullara, Valentina; La Vignera, Sandro; Calogero, Aldo E

    2017-05-01

    Reactive oxygen species favor reproductive processes at low concentrations, but damage spermatozoa and decrease their fertilizing capacity at high concentrations. During infection and/or inflammation of the accessory sex glands reactive oxygen species overproduction may occur which, in turn, may negatively impact on sperm motility, sperm DNA fragmentation, and lipid peroxidation. A number of nutraceutical formulations containing antioxidant molecules have been developed to counteract the deleterious effects of the oxidative stress. A recent formulation containing zinc, D-aspartic acid, and coenzyme-Q10 is present in the pharmaceutical market. Based on these premises, the aim of the present study was to evaluate the effects of this combination on spermatozoa in vitro. The study was conducted on 24 men (32.2 ± 5.5 years): 12 normozoospermic men and 12 asthenozoospermic patients. Spermatozoa from each sample were divided into two control aliquots (aliquot A and B) and an aliquot incubated with zinc, D-aspartic acid, and coenzyme-Q10 (aliquot C). After 3 h of incubation, the following parameters were evaluated: progressive motility, number of spermatozoa with progressive motility recovered after swim-up, lipid peroxidation, and DNA fragmentation. Incubation with zinc, D-aspartic acid, and coenzyme-Q10 maintained sperm motility in normozoospermic men (37.7 ± 1.2 % vs. 35.8 ± 2.3 % at time zero) and improved it significantly in asthenozoospermic patients (26.5 ± 1.9 % vs. 18.8 ± 2.0 % at time zero) (p aspartic acid, and coenzyme-Q10 (p < 0.05) in both normozospermic men (1.0 ± 0.4 % vs. 2.4 ± 0.9 %) and asthenozooseprmic patients (0.2 ± 0.1 % vs. 0.6 ± 0.2 %). No statistically significant effect was observed on sperm DNA fragmentation. This nutraceutical formulation may be indicated in vitro during the separation of the spermatozoa in the assisted reproduction techniques, during which the spermatozoa

  7. Patients with medium-chain acyl-coenzyme a dehydrogenase deficiency have impaired oxidation of fat during exercise but no effect of L-carnitine supplementation

    DEFF Research Database (Denmark)

    Madsen, K L; Preisler, N; Orngreen, M C

    2013-01-01

    It is not clear to what extent skeletal muscle is affected in patients with medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD). l-Carnitine is commonly used as a supplement in patients with MCADD, although its beneficial effect has not been verified.......It is not clear to what extent skeletal muscle is affected in patients with medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD). l-Carnitine is commonly used as a supplement in patients with MCADD, although its beneficial effect has not been verified....

  8. The effect of long-term treatment with coenzyme Q10 on nucleic acid modifications by oxidation in children with Down syndrome

    DEFF Research Database (Denmark)

    Larsen, Emil List; Padella, Lucia; Bergholdt, Helle Kirstine Mørup

    2018-01-01

    Elevated levels of oxidative nucleic acid modifications have been proposed to be associated with some of the clinical characteristics of Down syndrome. Oral intake of coenzyme Q10 improves oxidative status and shows a tendency toward protective effect on DNA oxidation in certain age groups...... of children with Down syndrome. Here, we demonstrate that long-term (i.e., 4 years) treatment with coenzyme Q10 (ubiquinone) at the dosage of 4 mg/kg/d does not affect whole body DNA and RNA oxidation....

  9. Coenzyme Q10 production in plants: current status and future prospects.

    Science.gov (United States)

    Parmar, Sanjay Singh; Jaiwal, Anjali; Dhankher, Om Parkash; Jaiwal, Pawan K

    2015-06-01

    Coenzyme Q10 (CoQ10) or Ubiquinone10 (UQ10), an isoprenylated benzoquinone, is well-known for its role as an electron carrier in aerobic respiration. It is a sole representative of lipid soluble antioxidant that is synthesized in our body. In recent years, it has been found to be associated with a range of patho-physiological conditions and its oral administration has also reported to be of therapeutic value in a wide spectrum of chronic diseases. Additionally, as an antioxidant, it has been widely used as an ingredient in dietary supplements, neutraceuticals, and functional foods as well as in anti-aging creams. Since its limited dietary uptake and decrease in its endogenous synthesis in the body with age and under various diseases states warrants its adequate supply from an external source. To meet its growing demand for pharmaceutical, cosmetic and food industries, there is a great interest in the commercial production of CoQ10. Various synthetic and fermentation of microbial natural producers and their mutated strains have been developed for its commercial production. Although, microbial production is the major industrial source of CoQ10 but due to low yield and high production cost, other cost-effective and alternative sources need to be explored. Plants, being photosynthetic, producing high biomass and the engineering of pathways for producing CoQ10 directly in food crops will eliminate the additional step for purification and thus could be used as an ideal and cost-effective alternative to chemical synthesis and microbial production of CoQ10. A better understanding of CoQ10 biosynthetic enzymes and their regulation in model systems like E. coli and yeast has led to the use of metabolic engineering to enhance CoQ10 production not only in microbes but also in plants. The plant-based CoQ10 production has emerged as a cost-effective and environment-friendly approach capable of supplying CoQ10 in ample amounts. The current strategies, progress and constraints of

  10. Coenzyme Q10 Supplementation and Oocyte Aneuploidy in Women Undergoing IVF-ICSI Treatment

    Directory of Open Access Journals (Sweden)

    Yaakov Bentov

    2014-01-01

    Full Text Available Background The age-related reduction in live-birth rate is attributed to a high rate of aneuploidy and follicle depletion. We showed in an animal model that treatment with Coenzyme Q10 (CoQ10 markedly improved reproductive outcome. The aim of this study was to compare the post-meiotic oocyte aneuploidy rate in in vitro fertilization (IVF and intra cytoplasmic sperm injection (ICSI patients treated with CoQ10 or placebo. Methods We conducted a double blind placebo controlled randomized trial that included IVF-ICSI patients 35-43 years of age. The patients were treated with either 600 mg of CoQ10 or an equivalent number of placebo caps. We compared the post-meiotic aneuploidy rate using polar body biopsy (PBBX and comparative genomic hybridization (CGH. According to the power calculation, 27 patients were needed for each arm. Results Owing to safety concerns regarding the effects of polar body biopsy on embryo quality and implantation, the study was terminated before reaching the target number of participants. A total of 39 patients were evaluated and randomized (17 CoQ10, 22 placebo, 27 were given the study medication (12 CoQ10, 15 placebo, and 24 completed an IVF-ICSI cycle including PBBX and embryo transfer (10 CoQ10, 14 placebo. Average age, base line follicle stimulating hormone (FSH, peak estradiol and progesterone serum level, as well as the total number of human menopausal gonadotropin (hMG units–-did not differ between the groups. The rate of aneuploidy was 46.5% in the CoQ10 group compared to 62.8% in the control. Clinical pregnancy rate was 33% for the CoQ10 group and 26.7% for the control group. Conclusion No significant differences in outcome were detected between the CoQ10 and placebo groups. However, the final study was underpowered to detect a difference in the rate of aneuploidy.

  11. Supplementing in the diet of lactating Holstein cows may naturally produce coenzyme Q10-enriched milk

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    Gui-Seck Bae

    2018-01-01

    Full Text Available Objective To examine the effects of Rhodobacter sphaeroides (R. sphaeroides supplementation as a direct-fed microbial (DFM on rumen fermentation in dairy cows and on coenzyme Q10 (CoQ10 transition into milk, an in vitro rumen simulation batch culture and an in vivo dairy cow experiment were conducted. Methods The characteristics of in vitro ruminal fermentation were investigated using rumen fluids from six cannulated Holstein dairy cows at 2 h post-afternoon feeding. A control treatment was included in the experiments based on a typified total mixed ration (TMR for lactating dairy cows, which was identical to the one used in the in vivo study, plus R. sphaeroides at 0.1%, 0.3%, and 0.5% TMR dry matter. The in vivo study employed six ruminally cannulated lactating Holstein cows randomly allotted to either the control TMR (C-TMR treatment or to a diet supplemented with a 0.5% R. sphaeroides culture (S-TMR, dry matter basis ad libitum. The presence of R. sphaeroides was verified using denaturing gradient gel electrophoresis (DGGE applied to the bacterial samples obtained from the in vivo study. The concentration of CoQ10 in milk and in the supernatant from the in vitro study was determined using high performance liquid chromatography. Results The results of the in vitro batch culture and DGGE showed that the concentration of CoQ10 significantly increased after 2 h of R. sphaeroides supplementation above 0.1%. When supplemented to the diet of lactating cows at the level of 0.5%, R. sphaeroides did not present any adverse effect on dry matter intake and milk yield. However, the concentration of CoQ10 in milk dramatically increased, with treated cows producing 70.9% more CoQ10 than control cows. Conclusion The CoQ10 concentration in milk increased via the use of a novel DFM, and R. sphaeroides might be used for producing value-added milk and dairy products in the future.

  12. Analysis of hydroxycinnamic acid degradation in Agrobacterium fabrum reveals a coenzyme A-dependent, beta-oxidative deacetylation pathway.

    Science.gov (United States)

    Campillo, Tony; Renoud, Sébastien; Kerzaon, Isabelle; Vial, Ludovic; Baude, Jessica; Gaillard, Vincent; Bellvert, Floriant; Chamignon, Cécile; Comte, Gilles; Nesme, Xavier; Lavire, Céline; Hommais, Florence

    2014-06-01

    The soil- and rhizosphere-inhabiting bacterium Agrobacterium fabrum (genomospecies G8 of the Agrobacterium tumefaciens species complex) is known to have species-specific genes involved in ferulic acid degradation. Here, we characterized, by genetic and analytical means, intermediates of degradation as feruloyl coenzyme A (feruloyl-CoA), 4-hydroxy-3-methoxyphenyl-β-hydroxypropionyl-CoA, 4-hydroxy-3-methoxyphenyl-β-ketopropionyl-CoA, vanillic acid, and protocatechuic acid. The genes atu1416, atu1417, and atu1420 have been experimentally shown to be necessary for the degradation of ferulic acid. Moreover, the genes atu1415 and atu1421 have been experimentally demonstrated to be essential for this degradation and are proposed to encode a phenylhydroxypropionyl-CoA dehydrogenase and a 4-hydroxy-3-methoxyphenyl-β-ketopropionic acid (HMPKP)-CoA β-keto-thiolase, respectively. We thus demonstrated that the A. fabrum hydroxycinnamic degradation pathway is an original coenzyme A-dependent β-oxidative deacetylation that could also transform p-coumaric and caffeic acids. Finally, we showed that this pathway enables the metabolism of toxic compounds from plants and their use for growth, likely providing the species an ecological advantage in hydroxycinnamic-rich environments, such as plant roots or decaying plant materials.

  13. Bioinspired Design of Alcohol Dehydrogenase@nano TiO2 Microreactors for Sustainable Cycling of NAD+/NADH Coenzyme

    Directory of Open Access Journals (Sweden)

    Sen Lin

    2018-02-01

    Full Text Available The bioinspired design and construction of enzyme@capsule microreactors with specific cell-like functionality has generated tremendous interest in recent years. Inspired by their fascinating complexity, scientists have endeavored to understand the essential aspects of a natural cell and create biomimicking microreactors so as to immobilize enzymes within the hierarchical structure of a microcapsule. In this study, simultaneous encapsulation of alcohol dehydrogenase (ADH was achieved during the preparation of microcapsules by the Pickering emulsion method using amphiphilic modified TiO2 nanoparticles (NPs as building blocks for assembling the photocatalytic microcapsule membrane. The ADH@TiO2 NP microreactors exhibited dual catalytic functions, i.e., spatially confined enzymatic catalysis and the membrane-associated photocatalytic oxidation under visible light. The sustainable cycling of nicotinamide adenine dinucleotide (NAD coenzyme between NADH and NAD+ was realized by enzymatic regeneration of NADH from NAD+ reduction, and was provided in a form that enabled further photocatalytic oxidation to NAD+ under visible light. This bioinspired ADH@TiO2 NP microreactor allowed the linking of a semiconductor mineral-based inorganic photosystem to enzymatic reactions. This is a first step toward the realization of sustainable biological cycling of NAD+/NADH coenzyme in synthetic functional microsystems operating under visible light irradiation.

  14. Role of coenzyme Q10 (CoQ10) in cardiac disease, hypertension and Meniere-like syndrome.

    Science.gov (United States)

    Kumar, Adarsh; Kaur, Harharpreet; Devi, Pushpa; Mohan, Varun

    2009-12-01

    Coenzyme Q10 (ubiquinone) is a mitochondrial coenzyme which is essential for the production of ATP. Being at the core of cellular energy processes it assumes importance in cells with high energy requirements like the cardiac cells which are extremely sensitive to CoQ10 deficiency produced by cardiac diseases. CoQ10 has thus a potential role for prevention and treatment of heart ailments by improving cellular bioenergetics. In addition it has an antioxidant, a free radical scavenging and a vasodilator effect which may be helpful in these conditions. It inhibits LDL oxidation and thus the progression of atherosclerosis. It decreases proinflammatory cytokines and decreases blood viscosity which is helpful in patients of heart failure and coronary artery disease. It also improves ischemia and reperfusion injury of coronary revascularisation. Significant improvement has been observed in clinical and hemodynamic parameters and in exercise tolerance in patients given adjunctive CoQ10 in doses from 60 to 200 mg daily in the various trials conducted in patients of heart failure, hypertension, ischemic heart disease and other cardiac illnesses. Recently it has been found to be an independent predictor of mortality in congestive heart failure. It has also been found to be helpful in vertigo and Meniere-like syndrome by improving the immune system. Further research is going on to establish firmly its role in the therapy of cardiovascular diseases.

  15. THE COMBINED EFFECT OF SCUTELLARIA BAICALENSIS EXTRACT AND COENZYME Q10 IN OXIDATIVE STRESS INDUCED BY CHROMIUM COMPOUNDS

    Directory of Open Access Journals (Sweden)

    Ewa Sawicka

    2010-03-01

    Full Text Available Background: The common use of antioxidants and its joint application brings the question whether they are useful in oxidative stress induced by the chemicals or whether they cause harmful interaction. Both Scutellaria baicalensis and CoQ10 are known as antioxidants, however one exogenous, the second endogenous. Chromium belongs equal to essential microelements and toxic factors. Therefore the aim of work was the evaluation joint effect of two examined antioxidants in exposure to chromium compounds.Materials and methods: The material was fresh blood obtained from healthy volunteers. The concentration of malondialdehyde (MDA in erythrocytes was evaluated using Stock’s method. The activity of mixture of Antoxyd and coenzyme Q10 was tested after exposure to chromium III and VI at concentrations: 0,05; 0,5 and 1,0 µg/ml. Antioxidants were used in concentrations : 8,0; 20; 60 and 100 µg/ml. Results: The influence of coenzyme Q10 in exposure to chromium III and chromium VI was statistically insignificant, but CoQ10 given together with Antoxyd in all used concentration statistically significant decreased the level of MDA in erythrocytes exposed to chromium compounds (p*0,001. Conclusions: Application of both antioxidants has exerted synergistic action lowering MDA level, which was elevated after chromium. No harmful interactions in the examined sample between antioxidants and chromium ions were noted.

  16. Coenzyme Q Biosynthesis: Evidence for a Substrate Access Channel in the FAD-Dependent Monooxygenase Coq6.

    Directory of Open Access Journals (Sweden)

    Alexandre Ismail

    2016-01-01

    Full Text Available Coq6 is an enzyme involved in the biosynthesis of coenzyme Q, a polyisoprenylated benzoquinone lipid essential to the function of the mitochondrial respiratory chain. In the yeast Saccharomyces cerevisiae, this putative flavin-dependent monooxygenase is proposed to hydroxylate the benzene ring of coenzyme Q (ubiquinone precursor at position C5. We show here through biochemical studies that Coq6 is a flavoprotein using FAD as a cofactor. Homology models of the Coq6-FAD complex are constructed and studied through molecular dynamics and substrate docking calculations of 3-hexaprenyl-4-hydroxyphenol (4-HP6, a bulky hydrophobic model substrate. We identify a putative access channel for Coq6 in a wild type model and propose in silico mutations positioned at its entrance capable of partially (G248R and L382E single mutations or completely (a G248R-L382E double-mutation blocking access to the channel for the substrate. Further in vivo assays support the computational predictions, thus explaining the decreased activities or inactivation of the mutated enzymes. This work provides the first detailed structural information of an important and highly conserved enzyme of ubiquinone biosynthesis.

  17. Binding site for the adenosyl group of coenzyme B12 in diol dehydrase

    International Nuclear Information System (INIS)

    Toraya, T.

    1985-01-01

    The binding of cob(II)alamin (CblII) and 5'-deoxyadenosine to diol dehydrase was studied spectroscopically and with [U- 14 C]5'-deoxyadenosine. CblII was bound to this enzyme forming a tight 1:1 complex which was resistant to oxidation by O 2 even in the presence of CN-. An irreversible 1:1:1 ternary complex was formed between enzyme, CblII, and 5'-deoxyadenosine, when the enzyme was incubated first with the nucleoside and then with CblII. When this order of addition of the constituents was reversed, no 5'-deoxyadenosine was bound to the enzyme-CblII complex. Hydroxocobalamin could also bind to the enzyme together with the nucleoside, while other cob(III)alamins bearing a bulkier Co beta ligand displaced the nucleoside upon binding to the enzyme. The binding of [U- 14 C]5'-deoxyadenosine was strongly inhibited by unlabeled 5'-deoxy-ara-adenosine, 4',5'-anhydroadenosine, adenosine, adenine, and 5',8-cyclic adenosine, in this order, but not by 5'-deoxyuridine. These results constitute direct evidence for the presence of the binding site for the adenosyl group of adenosylcobalamin, which is spatially limited to and highly specific for adenine nucleosides. The binding of 5'-deoxyadenosine to the apoenzyme was reversible

  18. Genetic Basis for Correction of Very‐Long‐Chain Acyl-Coenzyme A Dehydrogenase Deficiency by Bezafibrate in Patient Fibroblasts: Toward a Genotype‐Based Therapy

    DEFF Research Database (Denmark)

    Gobin‐Limballe, S.; Djouadi, F.; Aubey, F.

    2007-01-01

    Very‐long‐chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency is an inborn mitochondrial fatty‐acid β‐oxidation (FAO) defect associated with a broad mutational spectrum, with phenotypes ranging from fatal cardiopathy in infancy to adolescent‐onset myopathy, and for which there is no established...

  19. A de novo NADPH generation pathway for improving lysine production of Corynebacterium glutamicum by rational design of the coenzyme specificity of glyceraldehyde 3-phosphate dehydrogenase.

    Science.gov (United States)

    Bommareddy, Rajesh Reddy; Chen, Zhen; Rappert, Sugima; Zeng, An-Ping

    2014-09-01

    Engineering the cofactor availability is a common strategy of metabolic engineering to improve the production of many industrially important compounds. In this work, a de novo NADPH generation pathway is proposed by altering the coenzyme specificity of a native NAD-dependent glyceraldehyde 3-phosphate dehydrogenase (GAPDH) to NADP, which consequently has the potential to produce additional NADPH in the glycolytic pathway. Specifically, the coenzyme specificity of GAPDH of Corynebacterium glutamicum is systematically manipulated by rational protein design and the effect of the manipulation for cellular metabolism and lysine production is evaluated. By a combinatorial modification of four key residues within the coenzyme binding sites, different GAPDH mutants with varied coenzyme specificity were constructed. While increasing the catalytic efficiency of GAPDH towards NADP enhanced lysine production in all of the tested mutants, the most significant improvement of lysine production (~60%) was achieved with the mutant showing similar preference towards both NAD and NADP. Metabolic flux analysis with (13)C isotope studies confirmed that there was no significant change of flux towards the pentose phosphate pathway and the increased lysine yield was mainly attributed to the NADPH generated by the mutated GAPDH. The present study highlights the importance of protein engineering as a key strategy in de novo pathway design and overproduction of desired products. Copyright © 2014 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  20. SLC1 and SLC4 encode partially redundant acyl-coenzyme A 1-acylglycerol-3-phosphate O-acyltransferases of budding yeast

    DEFF Research Database (Denmark)

    Benghezal, Mohammed; Roubaty, Carole; Veepuri, Vijayanath

    2007-01-01

    Phosphatidic acid is the intermediate, from which all glycerophospholipids are synthesized. In yeast, it is generated from lysophosphatidic acid, which is acylated by Slc1p, an sn-2-specific, acyl-coenzyme A-dependent 1-acylglycerol-3-phosphate O-acyltransferase. Deletion of SLC1 is not lethal...

  1. 3-Methylcrotonyl-coenzyme A carboxylase deficiency in Amish/Mennonite adults identified by detection of increased acylcarnitines in blood spots of their children.

    Science.gov (United States)

    Gibson, K M; Bennett, M J; Naylor, E W; Morton, D H

    1998-03-01

    Isolated 3-methylcrotonyl coenzyme A carboxylase (MCC) deficiency was documented in four adult women from the Amish/Mennonite population of Lancaster County, Pennsylvania. Metabolic and enzymatic investigations in these individuals were instituted after the detection of abnormal acylcarnitine profiles in blood spots obtained from their newborn children, in whom MCC activity was normal.

  2. A single nucleotide polymorphism within the acetyl-coenzyme A carboxylase beta gene is associated with proteinuria in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Maeda, Shiro; Kobayashi, Masa-aki; Araki, Shin-ichi

    2010-01-01

    It has been suggested that genetic susceptibility plays an important role in the pathogenesis of diabetic nephropathy. A large-scale genotyping analysis of gene-based single nucleotide polymorphisms (SNPs) in Japanese patients with type 2 diabetes identified the gene encoding acetyl-coenzyme A ca...

  3. Copper (II)

    African Journals Online (AJOL)

    CLEMENT O BEWAJI

    Valine (2 - amino - 3 – methylbutanoic acid), is a chemical compound containing .... Stability constant (Kf). Gibb's free energy. ) (. 1. −. ∆. Mol. JG. [CuL2(H2O)2] ... synthesis and characterization of Co(ii), Ni(ii), Cu (II), and Zn(ii) complexes with ...

  4. Coenzyme Q10 and its effects in the treatment of neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Graciela Cristina dos Santos

    2009-12-01

    Full Text Available According to clinical and pre-clinical studies, oxidative stress and its consequences may be the cause or, at least, a contributing factor, to a large number of neurodegenerative diseases. These diseases include common and debilitating disorders, characterized by progressive and irreversible loss of neurons in specific regions of the brain. The most common neurodegenerative diseases are Parkinson's disease, Huntington's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Coenzyme Q10 (CoQ10 has been extensively studied since its discovery in 1957. It is a component of the electron transportation chain and participates in aerobic cellular respiration, generating energy in the form of adenosine triphosphate (ATP. The property of CoQ10 to act as an antioxidant or a pro-oxidant, suggests that it also plays an important role in the modulation of redox cellular status under physiological and pathological conditions, also performing a role in the ageing process. In several animal models of neurodegenerative diseases, CoQ10 has shown beneficial effects in reducing disease progression. However, further studies are needed to assess the outcome and effectiveness of CoQ10 before exposing patients to unnecessary health risks at significant costs.De acordo com estudos clínicos e pré-clínicos, o estresse oxidativo e suas conseqüências podem ser a causa, ou, no mínimo, o fator que contribui para grande número de doenças degenerativas. Estas doenças incluem problemas comuns e debilitantes, caracterizados por perda progressiva e irreversível de neurônios em regiões específicas do cérebro. As doenças degenerativas mais comuns são doença de Parkinson, de Hutington, de Alzheimer e esclerose amiotrófica lateral. A Coenzima Q10 (CoQ10 tem sido intensamente estudada desde sua descoberta, em 1957. É um componente da cadeia de transporte eletrônico e participa da respiração aeróbica celular, gerando energia na forma de trifosfato de

  5. Interdependence of coenzyme-induced conformational work and binding potential in yeast alcohol and porcine heart lactate dehydrogenases: a hydrogen-deuterium exchange study

    International Nuclear Information System (INIS)

    De Weck, Z.; Pande, J.; Kaegi, J.H.R.

    1987-01-01

    Binding of NAD coenzymes to yeast alcohol dehydrogenase (YADH) and porcine heart lactate dehydrogenase (PHLDH) was studied by hydrogen-deuterium exchange with the infrared technique. Conformational changes in the enzymes specific to the coenzymes and their fragments were observed, and the pH dependence of the exchange reaction shows that it conforms to the EX-2 scheme. In both YADH and PHLDH the magnitude of the conformational change as measured by exchange retardation is considerably larger for the NAD + than for NADH. Studies with coenzyme fragments like ADP-ribose, ADP, and AMP also highlight the lack of rigorous correlation between structural features such as charge and size and their influence on exchange behavior. Ternary complexes such as YADH-NAD + -pyrazole, PHLDH-NAD + -oxalate, and PHLDH-NADH-oxamate, which mimic the transition state, have a significantly more pronounced effect on exchange rates than the corresponding binary complexes. The outstanding feature of this study is the demonstration that in the binary enzyme-coenzyme complexes the more loosely bound NAD + is more effective in retarding exchange than the more firmly bound NADH. These differences are attributed to the unequal structural constraints exerted by the two coenzymes upon the enzymes, which translate to unequal expenditure of transconformational work in the formation of the two complexes. The opposing variation in the free energy of binding and the transconformational work expended can be viewed as an unequal partitioning of the net free energy gain resulting from the protein-ligand interaction into a binding term and that required for conformational change

  6. Crystal structure of tabtoxin resistance protein complexed with acetyl coenzyme A reveals the mechanism for beta-lactam acetylation.

    Science.gov (United States)

    He, Hongzhen; Ding, Yi; Bartlam, Mark; Sun, Fei; Le, Yi; Qin, Xincheng; Tang, Hong; Zhang, Rongguang; Joachimiak, Andrzej; Liu, Jinyuan; Zhao, Nanming; Rao, Zihe

    2003-01-31

    Tabtoxin resistance protein (TTR) is an enzyme that renders tabtoxin-producing pathogens, such as Pseudomonas syringae, tolerant to their own phytotoxins. Here, we report the crystal structure of TTR complexed with its natural cofactor, acetyl coenzyme A (AcCoA), to 1.55A resolution. The binary complex forms a characteristic "V" shape for substrate binding and contains the four motifs conserved in the GCN5-related N-acetyltransferase (GNAT) superfamily, which also includes the histone acetyltransferases (HATs). A single-step mechanism is proposed to explain the function of three conserved residues, Glu92, Asp130 and Tyr141, in catalyzing the acetyl group transfer to its substrate. We also report that TTR possesses HAT activity and suggest an evolutionary relationship between TTR and other GNAT members.

  7. Crystal structure of tabtoxin resistance protein complexed with acetyl coenzyme A reveals the mechanism for {beta}-lactam acetylation.

    Energy Technology Data Exchange (ETDEWEB)

    He, H.; Ding, Y.; Bartlam, M.; Sun, F.; Le, Y.; Qin, X.; Tang, H.; Zhang, R.; Joachimiak, A.; Liu, J.; Zhao, N.; Rao, Z.; Biosciences Division; Tsinghua Univ.; Chinese Academy of Science

    2003-01-31

    Tabtoxin resistance protein (TTR) is an enzyme that renders tabtoxin-producing pathogens, such as Pseudomonas syringae, tolerant to their own phytotoxins. Here, we report the crystal structure of TTR complexed with its natural cofactor, acetyl coenzyme A (AcCoA), to 1.55 {angstrom} resolution. The binary complex forms a characteristic 'V' shape for substrate binding and contains the four motifs conserved in the GCN5-related N-acetyltransferase (GNAT) superfamily, which also includes the histone acetyltransferases (HATs). A single-step mechanism is proposed to explain the function of three conserved residues, Glu92, Asp130 and Tyr141, in catalyzing the acetyl group transfer to its substrate. We also report that TTR possesses HAT activity and suggest an evolutionary relationship between TTR and other GNAT members.

  8. Microglial inhibitory mechanism of Coenzyme Q10 against Aβ (1-42 induced cognitive dysfunctions: possible behavioral, biochemical, cellular and histopathological alterations

    Directory of Open Access Journals (Sweden)

    Arti eSingh

    2015-11-01

    Full Text Available Rationale: Alzheimer’s disease (AD is a debilitating disease with complex pathophysiology. Amyloid beta (Aβ (1-42 is a reliable model of AD that recapitulates many aspects of human AD. Objective: The present study has been designed to investigate the neuroprotective potential of Coenzyme Q10 (CoQ10 and its modulation with minocycline (microglial inhibitor against Aβ (1-42 induced cognitive dysfunction in rats. Method: Intrahippocampal (i.h. Aβ (1-42 (1µg/µl; 4µl/site were administered followed by drug treatment with galantamine (2 mg/kg, CoQ10 (20 and 40 mg/kg, minocycline (50 and 100 mg/kg and their combinations for a period of 21 days. Various neurobehavioral parameters followed by biochemical, acetylcholinesterase (AChE level, proinflammatory markers (TNF-α, mitochondrial respiratory enzyme complexes (I-IV and histopathological examinations were assessed.Results: Aβ (1-42 administration significantly impaired cognitive performance in Morris water maze (MWM performance test, causes oxidative stress, raised AChE level, caused neuroinflammation, mitochondrial dysfunction and histopathological alterations as compared to sham treatment. Treatment with CoQ10 (20 and 40 mg/kg and minocycline (50 and 100 mg/kg alone for 21days significantly improved cognitive performance as evidenced by reduced transfer latency and increased time spent in target quadrant (TSTQ, reduced AChE activity, oxidative damage (reduced LPO, nitrite level and restored SOD, catalase and GHS levels, TNF-α level, restored mitochondrial respiratory enzyme complex (I, II, III, IV activities and histopathological alterations as compared to control (Aβ (1-42 treated animals group. Further, combination of minocycline (50 and 100 mg/kg with CoQ10 (20 and 40 mg/kg significantly modulate the protective effect of CoQ10 as compared to their effect alone. Conclusion: The present study suggests that the neuroprotective effect of CoQ10 could be due to its microglia inhibitory

  9. Interaction of Coenzyme Q10 with Liposomes and its Impact on Suppression of Selenite – Induced Experimental Cataract

    Directory of Open Access Journals (Sweden)

    Medhat Wahba Shafaa

    2018-03-01

    Full Text Available Purpose: To stress the influence of Coenzyme Q10 (CoQ10 on the structural properties of liposomes as model membranes and to investigate the possible role of CoQ10 or CoQ10 doped in liposomes when topically instilled as eye drops, in preventing cataract. Methods: The molecular interaction between liposomes and Coenzyme Q10 was examined using differential scanning calorimetry (DSC and Fourier transform infrared spectroscopy (FTIR. Rat pups were randomly divided into six groups comprising 15 pups. Group (1, control group. Group (2, untreated model of cataract, received a single subcutaneous injection of sodium selenite. Instillation of pure CoQ10 (Group 3, CoQ10 encapsulated into neutral (Group 4, positive (Group 5 and negative (Group 6 Dipalmitoyl phosphatidylcholine (DPPC liposomes on the opacification of lenses in rat pups after sodium selenite injection was topically received. Results: The incorporated CoQ10 is probably associated with lipid bilayers where it interacts to a large extent and perturbs them. This results in strong broadening and shift to lower temperature (94°C of the major characteristic endothermic peak of pure DPPC at 105°C. FTIR showed that the incorporation of CoQ10 into DPPC induces a conformational change in the polar region of DPPC. Ophthalmological and Biochemical studies revealed that CoQ10 alone followed by negatively charged liposomes doped with CoQ10 are more effective in reducing the progress of cataract as well as improving the lens soluble proteins levels and total antioxidant capacity. Conclusion: The interactions of CoQ10 with membrane systems may contribute to a better understanding of CoQ10 physiological properties and the development of therapeutically advanced systems.

  10. Activity of coenzyme Q 10 (Q-Ter multicomposite) on recovery time in noise-induced hearing loss.

    Science.gov (United States)

    Staffa, Paola; Cambi, Jacopo; Mezzedimi, Chiara; Passali, Desiderio; Bellussi, Luisa

    2014-01-01

    A potential consequence of exposure to noise is a temporary reduction in auditory sensitivity known as temporary threshold shift (TTS), which mainly depends on the intensity and duration of exposure to the noise. Recovery time is related to the amount of initial hearing loss, and the most recovery takes place during the first 15 min following exposure. This study evaluated the efficacy in otoprotection against noise-induced hearing loss of an orally administrated food supplement containing coenzyme Q 10 -Ter. This water-soluble formulation of coenzyme Q 10 shows better bioavailability than the native form and has been found to have a protective effect on outer hair cells after exposure to noise in animal models. Thirty volunteers were enrolled, and the right ear of each subject was exposed to a narrow-band noise centered at 3 kHz for 10 min at the intensity of 90 dB HL. In the 30 subjects enrolled, TTS was evaluated after 2, 15, and 30 min and the recovery time was recorded in each subject. The longest recovery time was 45 min. Among the 18 subjects who underwent a second test after treatment with Q-Ter, the mean recovery time was 31.43 min. The results of the present study show that 30 days' treatment with Q-Ter can aid faster recovery after exposure to noise (P < 0.0001). The reduction in the recovery time following treatment can be explained by Q-Ter-mediated improvement of the outer hair cells' response to oxidative stress.

  11. Addition of omega-3 fatty acid and coenzyme Q10 to statin therapy in patients with combined dyslipidemia.

    Science.gov (United States)

    Tóth, Štefan; Šajty, Matej; Pekárová, Tímea; Mughees, Adil; Štefanič, Peter; Katz, Matan; Spišáková, Katarína; Pella, Jozef; Pella, Daniel

    2017-07-26

    Statins represent a group of drugs that are currently indicated in the primary and secondary prevention of cardiovascular events. Their administration can be associated with side effects and the insufficient reduction of triacylglyceride (TAG) levels. This study aimed to assess the effect of the triple combination of statins with omega-3 fatty acids and coenzyme Q10 (CoQ10) on parameters associated with atherogenesis and statin side effects. In this pilot randomized double-blind trial, 105 subjects who met the criteria of combined dislipidemia and elevated TAG levels were randomly divided into three groups. In the control group, unaltered statin therapy was indicated. In the second and third groups, omega-3 PUFA 2.52 g/day (Zennix fa Pleuran) and omega-3 PUFA 2.52 g+CoQ10 200 mg/day (Pharma Nord ApS) were added, res//. At the end of the 3-month period (±1 week), all patients were evaluated. Significant reduction of hepatic enzymes activity, systolic blood preasure, inflammatory markers and TAG levels were detected in both groups in comparison to the control group. Activity of SOD and GPx increased significantly after additive therapy. Coenzyme Q10 addition significantly reduced most of the abovementioned parameters (systolic blood preasure, total cholesterol, LDL, hsCRP, IL-6, SOD) in comparison with the statin+omega-3 PUFA group. The intensity of statin adverse effects were significantly reduced in the group with the addition of CoQ10. The results of this pilot study suggest the possible beneficial effects of triple combination on the lipid and non-lipid parameters related to atherogenesis and side effects of statin treatment.

  12. Amelioration of Behavioural, Biochemical, and Neurophysiological Deficits by Combination of Monosodium Glutamate with Resveratrol/Alpha-Lipoic Acid/Coenzyme Q10 in Rat Model of Cisplatin-Induced Peripheral Neuropathy

    Directory of Open Access Journals (Sweden)

    Naini Bhadri

    2013-01-01

    Full Text Available Cisplatin or cis-diamminedichloroplatinum (II (CDDP is a cytotoxic chemotherapeutic agent with dose-dependent peripheral neuropathy as a foremost side effect characterised by ataxia, pain, and sensory impairment. Cumulative drug therapy of CDDP is known to produce severe oxidative damage. It mainly targets and accumulates in dorsal root ganglia that in turn cause damage resulting in secondary nerve fibre axonopathy. In the present study, we investigated the neuroprotective effect of the combination of monosodium glutamate (MSG with three individual antioxidants, that is, resveratrol, alpha-lipoic acid (ALA, and coenzyme Q10 (CoQ10, in cisplatin (2 mg/kg i.p. twice weekly induced peripheral neuropathy in rats. After 8 weeks of treatment the degree of neuroprotection was determined by measuring behavioral and electrophysiological properties and sciatic nerve lipid peroxidation, as well as glutathione and catalase levels. The results suggested that pretreatment with the combination of MSG (500 mg/kg/day po with resveratrol (10 mg/kg/day i.p. or ALA (20 mg/kg/day i.p. or CoQ10 (10 mg/kg weekly thrice i.p. exhibited neuroprotective effect. The maximum neuroprotection of MSG was observed in the combination with resveratrol.

  13. (II) complexes

    African Journals Online (AJOL)

    activities of Schiff base tin (II) complexes. Neelofar1 ... Conclusion: All synthesized Schiff bases and their Tin (II) complexes showed high antimicrobial and ...... Singh HL. Synthesis and characterization of tin (II) complexes of fluorinated Schiff bases derived from amino acids. Spectrochim Acta Part A: Molec Biomolec.

  14. HYPOLIPIDEMIC EFFECT OF CURCUMIN OR CO-ENZYME Q1-0 AND THEIR MIXTURE ON OBESE RATS FED A HIGH CHOLESTEROL DIET

    International Nuclear Information System (INIS)

    SHAHIN, M.I.M.

    2008-01-01

    In the current study, hyperlipidemia was induced in the rats by feeding diet enriched with cholesterol for two weeks. After 2 weeks of induction of hypercholesterolemia in rats and in comparison to normal rats, the results showed that incorporation of extra cholesterol in diet led to significant increases in serum cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, leptin and MDA levels. On the other hand, total serum triiodothyronine (T3), liver glutathione (GSH) and glutathione peroxidase (GPx) activities were decreased significantly in cholesterol fed rats. The concentration of TBARS in the liver was elevated.All previous parameters were corrected after the hypercholesterolemic rats were treated with curcumin or co-enzyme Q 1 -0 or a mixture of them dependent on the time of treatment. These findings are consistent with the concept that curcumin and co-enzyme Q 10 are antioxidant agents. The underlying mechanisms of these effects were discussed

  15. Reduced mitochondrial coenzyme Q10 levels in HepG2 cells treated with high-dose simvastatin: A possible role in statin-induced hepatotoxicity?

    International Nuclear Information System (INIS)

    Tavintharan, S.; Ong, C.N.; Jeyaseelan, K.; Sivakumar, M.; Lim, S.C.; Sum, C.F.

    2007-01-01

    Lowering of low-density lipoprotein cholesterol is well achieved by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins). Statins inhibit the conversion of HMG-CoA to mevalonate, a precursor for cholesterol and coenzyme Q10 (CoQ 10 ). In HepG2 cells, simvastatin decreased mitochondrial CoQ 10 levels, and at higher concentrations was associated with a moderately higher degree of cell death, increased DNA oxidative damage and a reduction in ATP synthesis. Supplementation of CoQ 10 , reduced cell death and DNA oxidative stress, and increased ATP synthesis. It is suggested that CoQ 10 deficiency plays an important role in statin-induced hepatopathy, and that CoQ 10 supplementation protects HepG2 cells from this complication

  16. Effect of dietary coenzyme Q10 supplementation on serum and bone minerals and leg weakness mortality in broilers

    Directory of Open Access Journals (Sweden)

    M. Gopi

    2014-05-01

    Full Text Available Aim: This work was carried out to study the effect of coenzyme Q10 supplementation on serum calcium and phosphorus levels, tibial bone weight, bone ash, bone calcium and phosphorus levels and mortality of birds due to leg weakness when the broilers were maintained under high environmental temperature. Materials and Methods: The trial was carried out on 216 Cobb400 broiler chicks and divided into four groups with nine replicates and each replicate consisting of six birds. The treatments include normal energy diet (NE (as per breeder's specifications (G1, high energy (HE (NE plus 100 kcal/kg diet without CoQ10 supplementation (G2, high energy diet supplemented with CoQ10 at 20 mg/kg (G3 and high energy diet supplemented with CoQ10 at 40 mg/kg (G4. The experiment was carried out when the temperature humidity index (THI ranged from 33.05 to 38.65oC for a period of 42 days. Results: The serum calcium and phosphorus levels in the G1, G2, G3 and G4 were 9.07 ± 0.22, 8.48 ± 0.10, 8.30 ± 0.10, 8.32 ± 0.12 and 4.90 ± 0.20, 4.06 ± 0.32, 3.96 ± 0.17, 4.02 ± 0.24, respectively. The tibial bone weight (g was 21.58 ± 1.32, 17.92 ± 1.90, 18.67 ± 1.30 and 17.42 ± 1.18; tibial bone Ash (% 46.67 ± 2.71, 44.48 ± 2.40, 44.66 ± 3.09 and 44.62 ± 1.74; Bone calcium (% 33.57 ± 0.2, 31.27 ± 0.55, 31.50 ± 0.45 and 31.47 ± 0.83, bone phosphorus (% was 11.86 ± 0.16, 10.38 ± 0.11, 10.68 ± 0.08 and 10.39 ± 0.17, respectively in G1, G2, G3 and G4 groups. The serum calcium and phosphorus levels were significantly higher (P<0.05 in G1 over the other three groups. The tibial bone weight was not altered by the energy level or the coenzyme Q10 supplementation. The tibial bone calcium and phosphorus levels were significantly higher in G1 than the other three groups. Conclusion: The supplementation of coenzyme Q10 did not alter the serum and tibial bone calcium and phosphorus levels. The leg abnormality associated mortality was significantly decreased in G3

  17. Crystallization and preliminary X-ray analysis of PaaAC, the main component of the hydroxylase of the Escherichia coli phenylacetyl-coenzyme A oxygenase complex

    International Nuclear Information System (INIS)

    Grishin, Andrey M.; Ajamian, Eunice; Zhang, Linhua; Cygler, Miroslaw

    2010-01-01

    The expression, purification, crystallization and preliminary crystallographic analysis of the PaaAC complex is reported. This is the main component of the E. coliphenylacetyl-coenzyme A oxygenase complex. The Escherichia coli paa operon encodes enzymes of the phenylacetic acid-utilization pathway that metabolizes phenylacetate in the form of a coenzyme A (CoA) derivative. The phenylacetyl-coenzyme A oxygenase complex, which has been postulated to contain five components designated PaaABCDE, catalyzes ring hydroxylation of phenylacetyl-CoA. The PaaAC subcomplex shows low sequence similarity to other bacterial multicomponent monooxygenases (BMMs) and forms a separate branch on the phylogenetic tree. PaaAC, which catalyzes the hydroxylation reaction, was purified and crystallized in the absence of a bound ligand as well as in complexes with CoA, 3-hydroxybutyryl-CoA, benzoyl-CoA and the true substrate phenylacetyl-CoA. Crystals of the ligand-free enzyme belonged to space group P2 1 2 1 2 1 and diffracted to 2.65 Å resolution, whereas complexes with CoA and its derivatives crystallized in space group P4 1 2 1 2 and diffracted to ∼2.0 Å resolution. PaaAC represents the first crystallized BMM hydroxylase that utilizes a CoA-linked substrate

  18. The glossyhead1 allele of acc1 reveals a principal role for multidomain acetyl-coenzyme a carboxylase in the biosynthesis of cuticular waxes by Arabidopsis

    KAUST Repository

    Lu, Shiyou

    2011-09-23

    A novel mutant of Arabidopsis (Arabidopsis thaliana), having highly glossy inflorescence stems, postgenital fusion in floral organs, and reduced fertility, was isolated from an ethyl methanesulfonate-mutagenized population and designated glossyhead1 (gsd1). The gsd1 locus was mapped to chromosome 1, and the causal gene was identified as a new allele of Acetyl-Coenzyme A Carboxylase1 (ACC1), a gene encoding the main enzyme in cytosolic malonyl-coenzyme A synthesis. This, to our knowledge, is the first mutant allele of ACC1 that does not cause lethality at the seed or early germination stage, allowing for the first time a detailed analysis of ACC1 function in mature tissues. Broad lipid profiling of mature gsd1 organs revealed a primary role for ACC1 in the biosynthesis of the very-long-chain fatty acids (C 20:0 or longer) associated with cuticular waxes and triacylglycerols. Unexpectedly, transcriptome analysis revealed that gsd1 has limited impact on any lipid metabolic networks but instead has a large effect on environmental stress-responsive pathways, especially senescence and ethylene synthesis determinants, indicating a possible role for the cytosolic malonyl-coenzyme A-derived lipids in stress response signaling. © 2011 American Society of Plant Biologists. All Rights Reserved.

  19. Thermodynamic and Structure Guided Design of Statin Based Inhibitors of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase

    Energy Technology Data Exchange (ETDEWEB)

    Sarver, Ronald W.; Bills, Elizabeth; Bolton, Gary; Bratton, Larry D.; Caspers, Nicole L.; Dunbar, James B.; Harris, Melissa S.; Hutchings, Richard H.; Kennedy, Robert M.; Larsen, Scott D.; Pavlovsky, Alexander; Pfefferkorn, Jeffrey A.; Bainbridge, Graeme (Pfizer)

    2008-10-02

    Clinical studies have demonstrated that statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) inhibitors, are effective at lowering mortality levels associated with cardiovascular disease; however, 2--7% of patients may experience statin-induced myalgia that limits compliance with a treatment regimen. High resolution crystal structures, thermodynamic binding parameters, and biochemical data were used to design statin inhibitors with improved HMGR affinity and therapeutic index relative to statin-induced myalgia. These studies facilitated the identification of imidazole 1 as a potent (IC{sub 50} = 7.9 nM) inhibitor with excellent hepatoselectivity (>1000-fold) and good in vivo efficacy. The binding of 1 to HMGR was found to be enthalpically driven with a {Delta}H of -17.7 kcal/M. Additionally, a second novel series of bicyclic pyrrole-based inhibitors was identified that induced order in a protein flap of HMGR. Similar ordering was detected in a substrate complex, but has not been reported in previous statin inhibitor complexes with HMGR.

  20. Coenzyme Q10 as a treatment for fatigue and depression in multiple sclerosis patients: A double blind randomized clinical trial.

    Science.gov (United States)

    Sanoobar, Meisam; Dehghan, Parvin; Khalili, Mohammad; Azimi, Amirreza; Seifar, Fatemeh

    2016-01-01

    Multiple sclerosis (MS) is the chronic inflammatory and demyelinating disorder of central nervous system which is accompanied with disability and negative life style changes such as fatigue and depression. The aim of this study is to investigate the effect of coenzyme Q10 (CoQ10) supplementation on fatigue and depression in patients with MS. We performed a randomized, double-blinded, placebo-controlled trial to determine the effect of CoQ10 supplement (500 mg/day) vs. placebo for 12 weeks. Fatigue symptoms were quantified by means of fatigue severity scale (FSS) and the Beck depression inventory (BDI) was used to assess depressive symptoms. A significant decrease of FSS was observed in CoQ10 group during the intervention (P = 0.001) and significant increase of FSS change was observed within placebo group (P = 0.001). Repeated measure analysis of variance showed a significant time-by-treatment interaction for FSS (baseline 41.5 ± 15.6 vs. endpoint 45 ± 13.6; F1,45 = 55.23, P multiple sclerosis.

  1. Downregulation of monocytic differentiation via modulation of CD147 by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.

    Directory of Open Access Journals (Sweden)

    Manda V Sasidhar

    Full Text Available CD147 is an activation induced glycoprotein that promotes the secretion and activation of matrix metalloproteinases (MMPs and is upregulated during the differentiation of macrophages. Interestingly, some of the molecular functions of CD147 rely on its glycosylation status: the highly glycosylated forms of CD147 induce MMPs whereas the lowly glycosylated forms inhibit MMP activation. Statins are hydroxy-methylglutaryl coenzyme A reductase inhibitors that block the synthesis of mevalonate, thereby inhibiting all mevalonate-dependent pathways, including isoprenylation, N-glycosylation and cholesterol synthesis. In this study, we investigated the role of statins in the inhibition of macrophage differentiation and the associated process of MMP secretion through modulation of CD147. We observed that differentiation of the human monocytic cell line THP-1 to a macrophage phenotype led to upregulation of CD147 and CD14 and that this effect was inhibited by statins. At the molecular level, statins altered CD147 expression, structure and function by inhibiting isoprenylation and N-glycosylation. In addition, statins induced a shift of CD147 from its highly glycosylated form to its lowly glycosylated form. This shift in N-glycosylation status was accompanied by a decrease in the production and functional activity of MMP-2 and MMP-9. In conclusion, these findings describe a novel molecular mechanism of immune regulation by statins, making them interesting candidates for autoimmune disease therapy.

  2. Downregulation of monocytic differentiation via modulation of CD147 by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.

    Science.gov (United States)

    Sasidhar, Manda V; Chevooru, Sai Krishnaveni; Eickelberg, Oliver; Hartung, Hans-Peter; Neuhaus, Oliver

    2017-01-01

    CD147 is an activation induced glycoprotein that promotes the secretion and activation of matrix metalloproteinases (MMPs) and is upregulated during the differentiation of macrophages. Interestingly, some of the molecular functions of CD147 rely on its glycosylation status: the highly glycosylated forms of CD147 induce MMPs whereas the lowly glycosylated forms inhibit MMP activation. Statins are hydroxy-methylglutaryl coenzyme A reductase inhibitors that block the synthesis of mevalonate, thereby inhibiting all mevalonate-dependent pathways, including isoprenylation, N-glycosylation and cholesterol synthesis. In this study, we investigated the role of statins in the inhibition of macrophage differentiation and the associated process of MMP secretion through modulation of CD147. We observed that differentiation of the human monocytic cell line THP-1 to a macrophage phenotype led to upregulation of CD147 and CD14 and that this effect was inhibited by statins. At the molecular level, statins altered CD147 expression, structure and function by inhibiting isoprenylation and N-glycosylation. In addition, statins induced a shift of CD147 from its highly glycosylated form to its lowly glycosylated form. This shift in N-glycosylation status was accompanied by a decrease in the production and functional activity of MMP-2 and MMP-9. In conclusion, these findings describe a novel molecular mechanism of immune regulation by statins, making them interesting candidates for autoimmune disease therapy.

  3. Identification and characterization of an archaeal ketopantoate reductase and its involvement in regulation of coenzyme A biosynthesis.

    Science.gov (United States)

    Tomita, Hiroya; Imanaka, Tadayuki; Atomi, Haruyuki

    2013-10-01

    Coenzyme A (CoA) biosynthesis in bacteria and eukaryotes is regulated primarily by feedback inhibition towards pantothenate kinase (PanK). As most archaea utilize a modified route for CoA biosynthesis and do not harbour PanK, the mechanisms governing regulation of CoA biosynthesis are unknown. Here we performed genetic and biochemical studies on the ketopantoate reductase (KPR) from the hyperthermophilic archaeon Thermococcus kodakarensis. KPR catalyses the second step in CoA biosynthesis, the reduction of 2-oxopantoate to pantoate. Gene disruption of TK1968, whose product was 20-29% identical to previously characterized KPRs from bacteria/eukaryotes, resulted in a strain with growth defects that were complemented by addition of pantoate. The TK1968 protein (Tk-KPR) displayed reductase activity specific for 2-oxopantoate and preferred NADH as the electron donor, distinct to the bacterial/eukaryotic NADPH-dependent enzymes. Tk-KPR activity decreased dramatically in the presence of CoA and KPR activity in cell-free extracts was also inhibited by CoA. Kinetic studies indicated that CoA inhibits KPR by competing with NADH. Inhibition of ketopantoate hydroxymethyltransferase, the first enzyme of the pathway, by CoA was not observed. Our results suggest that CoA biosynthesis in T. kodakarensis is regulated by feedback inhibition of KPR, providing a feasible regulation mechanism of CoA biosynthesis in archaea. © 2013 John Wiley & Sons Ltd.

  4. Affinity labeling and resonance energy transfer studies of the reduced coenzyme regulatory site of bovine liver glutamate dehydrogenase

    International Nuclear Information System (INIS)

    Lark, R.H.

    1988-01-01

    Bovine liver glutamate dehydrogenase was studied by affinity labeling and resonance energy transfer. The enzyme uses the 2', 3'-dialdehyde derivative of NADPH (oNADPH) in the reductive amination of α-ketoglutarate. A 300 min enzyme incubation with 250 μM oNADPH at pH 8.0 leads to a covalent incorporation of 1 mol oNADPH/mol enzyme subunit. Similar rate constants are measured when assaying the change in inhibition by 600 μM NADH or by 1 μM GTP, suggesting that inhibition loss at the two regulatory sites results from oNADPH reaction at one location. oNADPH-modified enzyme is still 93% inhibited by saturating GTP concentrations. The presence of 5 mM NADS(P)H plus 200 μM GTP prevents the kinetic changes and reduces the incorporation of oNADPH. oNADPH is concluded to modify the reduced coenzyme regulatory site, and GTP affects the binding of ligands to this site. The linkage between glutamate dehydrogenase and [ 14 C]oNADPH proved too labile to allow isolation of a radioactive modified peptide. Three corrections in the amino acid sequence were made after sequencing peptides. Resonance energy transfer was used to measure the distance between sites on the enzyme

  5. Effect of DHA and CoenzymeQ10 Against Aβ- and Zinc-Induced Mitochondrial Dysfunction in Human Neuronal Cells

    Directory of Open Access Journals (Sweden)

    Nadia Sadli

    2013-07-01

    Full Text Available Background: Beta-amyloid (Aβ protein is a key factor in the pathogenesis of Alzheimer's disease (AD and it has been reported that mitochondria is involved in the biochemical pathway by which Aβ can lead to neuronal dysfunction. Coenzyme Q10 (CoQ10 is an essential cofactor involved in the mitochondrial electron transport chain and has been suggested as a potential therapeutic agent in AD. Zinc toxicity also affects cellular energy production by decreasing oxygen consumption rate (OCR and ATP turnover in human neuronal cells, which can be restored by the neuroprotective effect of docosahexaenoic acid (DHA. Method: In the present study, using Seahorse XF-24 Metabolic Flux Analysis we investigated the effect of DHA and CoQ10 alone and in combination against Aβ- and zinc-mediated changes in the mitochondrial function of M17 neuroblastoma cell line. Results: Here, we observed that DHA is specifically neuroprotective against zinc-triggered mitochondrial dysfunction, but does not directly affect Aβ neurotoxicity. CoQ10 has shown to be protective against both Aβ- and zinc-induced alterations in mitochondrial function. Conclusion: Our results indicate that DHA and CoQ10 may be useful for the prevention, treatment and management of neurodegenerative diseases such as AD.

  6. Comparative evaluation of coenzyme Q10-based gel and 0.8% hyaluronic acid gel in treatment of chronic periodontitis

    Directory of Open Access Journals (Sweden)

    Varun Sharma

    2016-01-01

    Full Text Available Background: The anti-inflammatory and immune enhancing effects of coenzyme Q10 (CoQ10 and hyaluronic acid are well established in medical literature. The present study was undertaken to evaluate their role in chronic periodontitis. Materials and Methods: One hundred twenty sites in 24 patients with clinically confirmed periodontitis were included in the study. A split-mouth design was used for intrasulcular application of CoQ10as adjunct to scaling and root planing (SRP, 0.8% hyaluronic acid as adjunct to SRP and SRP alone. Clinical parameters such as plaque index (PI, gingival color change index (GCCI, Eastman interdental bleeding index (EIBI, pocket depth (PD, and clinical attachment level (CAL were recorded. All the clinical parameters PI, EIBI, GCCI, PD, and CAL were recorded at baseline before SRP. Only PI, EIBI, and GCCI were recorded at 1st and 2nd week. Twenty-one days post 2nd week, i.e., 6th week all the clinical parameters were recorded again. Results: Intragroup analysis of all the clinical parameters showed clinical significant results between baseline and 6th week. However, on intergroup analysis, the results were not significant. Conclusion: The local application of CoQ10and hyaluronic acid gel in conjunction with SRP may have a beneficial effect on periodontal health in patients with chronic periodontitis.

  7. New evidences of neurotoxicity of aroclor 1254 in mice brain: potential of coenzyme q10 in abating the detrimental outcomes

    Directory of Open Access Journals (Sweden)

    Anuradha Majumdar

    2014-03-01

    Full Text Available Objectives The present subacute study was designed to evaluate the effect of coenzyme Q 10 (CoQ10 in the 28 days aroclor 1254 exposure induced oxidative stress in mice brain. Methods Biochemical estimations of brain lipid peroxidation (LPO, reduced glutathione (GSH, and activities of superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx and acetyl cholinesterase (AChE, and histopathological investigations of brain tissue were carried out. Results Oral exposure of aroclor 1254 (5 mg/kg led to significant decrease in levels of GSH, and activities of SOD, CAT, GPx, and AChE, and increase in LPO. These aberrations were restored by CoQ10 (10 mg/kg, intraperitoneal injection [IP]. This protection offered was comparable to that of L-deprenyl (1 mg/kg, IP which served as a reference standard. Conclusions Aroclor 1254 exposure hampers the activities of various antioxidant enzymes and induces oxidative stress in the brains of Swiss albino mice. Supplementation of CoQ10 abrogates these deleterious effects of aroclor 1254. CoQ10 also apparently enhanced acetyl cholinesterase activity which reflects its influence on the cholinergic system.

  8. Coenzyme Q Metabolism Is Disturbed in High Fat Diet-Induced Non Alcoholic Fatty Liver Disease in Rats

    Directory of Open Access Journals (Sweden)

    Kathleen M Botham

    2012-02-01

    Full Text Available Oxidative stress is believed to be a major contributory factor in the development of non alcoholic fatty liver disease (NAFLD, the most common liver disorder worldwide. In this study, the effects of high fat diet-induced NAFLD on Coenzyme Q (CoQ metabolism and plasma oxidative stress markers in rats were investigated. Rats were fed a standard low fat diet (control or a high fat diet (57% metabolizable energy as fat for 18 weeks. The concentrations of total (reduced + oxidized CoQ9 were increased by > 2 fold in the plasma of animals fed the high fat diet, while those of total CoQ10 were unchanged. Reduced CoQ levels were raised, but oxidized CoQ levels were not, thus the proportion in the reduced form was increased by about 75%. A higher percentage of plasma CoQ9 as compared to CoQ10 was in the reduced form in both control and high fat fed rats. Plasma protein thiol (SH levels were decreased in the high fat-fed rats as compared to the control group, but concentrations of lipid hydroperoxides and low density lipoprotein (LDL conjugated dienes were unchanged. These results indicate that high fat diet-induced NAFLD in rats is associated with altered CoQ metabolism and increased protein, but not lipid, oxidative stress.

  9. Improvement of Coenzyme Q10 Production: Mutagenesis Induced by High Hydrostatic Pressure Treatment and Optimization of Fermentation Conditions

    Directory of Open Access Journals (Sweden)

    Yahong Yuan

    2012-01-01

    Full Text Available Coenzyme Q10 (CoQ10, ubiquinone, a potent antioxidative dietary supplement, was produced by submerged fermentation using Agrobacterium tumefaciens instead of chemical synthesis or solvent extraction. Agrobacterium tumefaciens 1.2554 was subjected to mutagenesis using a series of treatments including high hydrostatic pressure (HHP treatment, UV irradiation, and diethyl sulfate (DES treatment to obtain mutant strains showing higher CoQ10 production than wild-type strains. A mutant strain PK38 with four genetic markers was isolated: the specific CoQ10 content of the mutant strain increased by 52.83% compared with the original strain. Effects of carbon and nitrogen sources on CoQ10 production with PK38 were studied. Sucrose at concentration of 30 g/l was tested as the best carbon source, and yeast extract at concentration of 30 g/l supplemented with 10 g/l of ammonium sulfate was identified to be the most favorable for CoQ10 production using PK38. Fed-batch culture strategy was then used for increasing production of CoQ10 in 5-l fermentor. Using the exponential feeding fed-batch culture of sucrose, cell growth and CoQ10 formation were significantly improved. With this strategy, the final cell biomass, CoQ10 production, and specific CoQ10 production increased by 126.11, 173.12, and 22.76%, respectively, compared to those of batch culture.

  10. Efficient Lewis Acid Ionic Liquid-Catalyzed Synthesis of the Key Intermediate of Coenzyme Q10 under Microwave Irradiation

    Directory of Open Access Journals (Sweden)

    Thomas Efferth

    2010-12-01

    Full Text Available An efficient synthesis of a valuable intermediate of coenzyme Q10 by microwave-assisted Lewis acidic ionic liquid (IL-catalyzed Friedel-Crafts alkylation is reported. The acidity of six [Etpy]BF4-based ionic liquids was characterized by means of the FT-IR technique using acetonitrile as a molecular probe. The catalytic activities of these ionic liquids were correlated with their Lewis acidity. With increasing Lewis acid strength of the ionic liquids, their catalytic activity in the Friedel-Crafts reaction increased, except for [Etpy]BF4-AlCl3. The effects of the reaction system, the molar fraction of Lewis acid in the Lewis acid ILs and heating techniques were also investigated. Among the six Lewis acid ionic liquids tested [Etpy]BF4-ZnCl2 showed the best catalytic activity, with a yield of 89% after a very short reaction time (150 seconds. This procedure has the advantages of higher efficiency, better reusability of ILs, energy conservation and eco-friendliness. The method has practical value for preparation of CoQ10 on an industrial scale.

  11. Topical treatment with coenzyme Q10-containing formulas improves skin's Q10 level and provides antioxidative effects.

    Science.gov (United States)

    Knott, Anja; Achterberg, Volker; Smuda, Christoph; Mielke, Heiko; Sperling, Gabi; Dunckelmann, Katja; Vogelsang, Alexandra; Krüger, Andrea; Schwengler, Helge; Behtash, Mojgan; Kristof, Sonja; Diekmann, Heike; Eisenberg, Tanya; Berroth, Andreas; Hildebrand, Janosch; Siegner, Ralf; Winnefeld, Marc; Teuber, Frank; Fey, Sven; Möbius, Janne; Retzer, Dana; Burkhardt, Thorsten; Lüttke, Juliane; Blatt, Thomas

    2015-01-01

    Ubiquinone (coenzyme Q10, Q10) represents an endogenously synthesized lipid-soluble antioxidant which is crucial for cellular energy production but is diminished with age and under the influence of external stress factors in human skin. Here, it is shown that topical Q10 treatment is beneficial with regard to effective Q10 replenishment, augmentation of cellular energy metabolism, and antioxidant effects. Application of Q10-containing formulas significantly increased the levels of this quinone on the skin surface. In the deeper layers of the epidermis the ubiquinone level was significantly augmented indicating effective supplementation. Concurrent elevation of ubiquinol levels suggested metabolic transformation of ubiquinone resulting from increased energy metabolism. Incubation of cultured human keratinocytes with Q10 concentrations equivalent to treated skin showed a significant augmentation of energy metabolism. Moreover, the results demonstrated that stressed skin benefits from the topical Q10 treatment by reduction of free radicals and an increase in antioxidant capacity. © 2015 International Union of Biochemistry and Molecular Biology.

  12. Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism

    Directory of Open Access Journals (Sweden)

    Camilla Ceccatelli Berti

    2015-04-01

    Full Text Available Mutations in nuclear genes associated with defective coenzyme A biosynthesis have been identified as responsible for some forms of neurodegeneration with brain iron accumulation (NBIA, namely PKAN and CoPAN. PKAN are defined by mutations in PANK2, encoding the pantothenate kinase 2 enzyme, that account for about 50% of cases of NBIA, whereas mutations in CoA synthase COASY have been recently reported as the second inborn error of CoA synthesis leading to CoPAN. As reported previously, yeast cells expressing the pathogenic mutation exhibited a temperature-sensitive growth defect in the absence of pantothenate and a reduced CoA content. Additional characterization revealed decreased oxygen consumption, reduced activities of mitochondrial respiratory complexes, higher iron content, increased sensitivity to oxidative stress and reduced amount of lipid droplets, thus partially recapitulating the phenotypes found in patients and establishing yeast as a potential model to clarify the pathogenesis underlying PKAN and CoPAN diseases.

  13. Coenzyme Q10, α-Tocopherol, and Oxidative Stress Could Be Important Metabolic Biomarkers of Male Infertility

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    Anna Gvozdjáková

    2015-01-01

    Full Text Available Oxidative stress, decreased antioxidant capacity, and impaired sperm mitochondrial function are the main factors contributing to male infertility. The goal of the present study was to assess the effect of the per os treatment with Carni-Q-Nol (440 mg L-carnitine fumarate + 30 mg ubiquinol + 75 IU vitamin E + 12 mg vitamin C in each softsule in infertile men on sperm parameters, concentration of antioxidants (coenzyme Q10,  CoQ10-TOTAL, γ, and α-tocopherols, and oxidative stress in blood plasma and seminal fluid. Forty infertile men were supplemented daily with two or three Carni-Q-Nol softsules. After 3 and 6 months of treatment, improved sperm density was observed (by 48.9% and 80.9%, resp. and after 3-month treatment the sperm pathology decreased by 25.8%. Concentrations of CoQ10-TOTAL (ubiquinone + ubiquinol and α-tocopherol were significantly increased and the oxidative stress was decreased. In conclusion, the effect of supplementary therapy with Carni-Q-Nol showed benefits on sperm function in men, resulting in 45% pregnancies of their women. We assume that assessment of oxidative stress, CoQ10-TOTAL, and α-tocopherol in blood plasma and seminal fluid could be important metabolic biomarkers in both diagnosis and treatment of male infertility.

  14. Activation of acetyl-coenzyme A carboxylase is involved in Taxol-induced ovarian cancer cell death.

    Science.gov (United States)

    Wu, Jiang; Ji, Fang; DI, Wen; Chen, Hongduo; Wan, Yinsheng

    2011-05-01

    Acetyl-coenzyme A carboxylase (ACC) is an attractive target for research into the treatment of a variety of human diseases, including diabetes, obesity and cancer. Mounting evidence suggests that the inhibition of ACC induced of cancer cell apoptosis. However, whether the inhibition of ACC regulates apoptosis in CaOV3 cancer cells has yet to be addressed. This study investigated the cytotoxic mechanism of action of ACC inhibition. Results showed that 5-(tetradecyloxy)-2-furoic acid (TOFA), an ACC inhibitor, enhanced Taxol-induced CaOV3 human ovarian cancer cell apoptosis. Notably, when TOFA was administered as a monotherapy, it induced CaOV3 cell apoptosis. Pre-treatment with the EGFR inhibitor PD153035 was found to markedly enhance ACC phosphorylation, whereas AMP-activated protein kinase (AMPK) activator AICAR was found to marginally enhance ACC phosphorylation. Taken together, the data showed ACC is a potential novel molecular target of Taxol. Additionally, ACC inhibition partially contributed to the cytotoxic effect of Taxol in ovarian cancer cells.

  15. Chromatin-remodeling SWI/SNF complex regulates coenzyme Q6 synthesis and a metabolic shift to respiration in yeast.

    Science.gov (United States)

    Awad, Agape M; Venkataramanan, Srivats; Nag, Anish; Galivanche, Anoop Raj; Bradley, Michelle C; Neves, Lauren T; Douglass, Stephen; Clarke, Catherine F; Johnson, Tracy L

    2017-09-08

    Despite its relatively streamlined genome, there are many important examples of regulated RNA splicing in Saccharomyces cerevisiae Here, we report a role for the chromatin remodeler SWI/SNF in respiration, partially via the regulation of splicing. We find that a nutrient-dependent decrease in Snf2 leads to an increase in splicing of the PTC7 transcript. The spliced PTC7 transcript encodes a mitochondrial phosphatase regulator of biosynthesis of coenzyme Q 6 (ubiquinone or CoQ 6 ) and a mitochondrial redox-active lipid essential for electron and proton transport in respiration. Increased splicing of PTC7 increases CoQ 6 levels. The increase in PTC7 splicing occurs at least in part due to down-regulation of ribosomal protein gene expression, leading to the redistribution of spliceosomes from this abundant class of intron-containing RNAs to otherwise poorly spliced transcripts. In contrast, a protein encoded by the nonspliced isoform of PTC7 represses CoQ 6 biosynthesis. Taken together, these findings uncover a link between Snf2 expression and the splicing of PTC7 and establish a previously unknown role for the SWI/SNF complex in the transition of yeast cells from fermentative to respiratory modes of metabolism. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Ratiometric colorimetric determination of coenzyme A using gold nanoparticles and a binuclear uranyl complex as optical probes

    International Nuclear Information System (INIS)

    Wu, Rurong; Liao, Lifu; Li, Shijun; Yang, Yanyan; Xiao, Xilin; Nie, Changming

    2016-01-01

    We describe a ratiometric colorimetric method for the determination of coenzyme A (CoA) by using gold nanoparticles (AuNPs) and bis-uranyl-bis-sulfosalophen (BUBSS) as optical probes. BUBSS is a binuclear uranyl complex and formed through the chelating reaction of two uranyl ions with bis-sulfosalophen. CoA is captured by the AuNPs via the thiol group and this leads to the formation of CoA-AuNPs. In a second step, BUBSS binds two CoA-AuNPs through a coordination reaction between the uranyl ions in BUBSS and the phosphate groups in CoA-AuNPs. This causes the CoA-AuNPs to aggregate and results in a color change from wine red to blue. A ratiometric colorimetric assay was established for CoA based on the ratiometric measurement of absorbance changes at 650 and 525 nm. Their ratio is linearly related to the concentration of CoA in the 0 to 1.2 μmol⋅L -1 range, with a 6 nmol⋅ L- 1 detection limit under optimal conditions. The method was successfully applied to the determination of CoA in spiked liver samples with recoveries between 99.4 and 102.6 %. (author)

  17. Anesthetic agents in patients with very long-chain acyl-coenzyme A dehydrogenase deficiency: a literature review.

    Science.gov (United States)

    Redshaw, Charlotte; Stewart, Catherine

    2014-11-01

    Very long-chain acyl-coenzyme A dehydrongenase deficiency (VLCADD) is a rare disorder of fatty acid metabolism that renders sufferers susceptible to hypoglycemia, liver failure, cardiomyopathy, and rhabdomyolysis. The literature about the management of these patients is hugely conflicting, suggesting that both propofol and volatile anesthesia should be avoided. We have reviewed the literature and have concluded that the source papers do not support the statements that volatile anesthetic agents are unsafe. The reports on rhabdomyolysis secondary to anesthesia appear to be due to inadequate supply of carbohydrate not volatile agents. Catabolism must be avoided with minimal fasting, glucose infusions based on age and weight, and attenuation of emotional and physical stress. General anesthesia appears to be protective of stress-induced catabolism and may offer benefits in children and anxious patients over regional anesthesia. Propofol has not been demonstrated to be harmful in VLCADD but is presented in an emulsion containing very long-chain fatty acids which can cause organ lipidosis and itself can inhibit mitochondrial fatty acid metabolism. It is therefore not recommended. Suxamethonium-induced myalgia may mimic symptoms of rhabdomyolysis and cause raised CK therefore should be avoided. Opioids, NSAIDS, regional anesthesia, and local anesthetic techniques have all been used without complication. © 2014 John Wiley & Sons Ltd.

  18. Overexpressing 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR in the lactococcal mevalonate pathway for heterologous plant sesquiterpene production.

    Directory of Open Access Journals (Sweden)

    Adelene Ai-Lian Song

    Full Text Available Isoprenoids are a large and diverse group of metabolites with interesting properties such as flavour, fragrance and therapeutic properties. They are produced via two pathways, the mevalonate pathway or the 2-C-methyl-D-erythritol-4-phosphate (MEP pathway. While plants are the richest source of isoprenoids, they are not the most efficient producers. Escherichia coli and yeasts have been extensively studied as heterologous hosts for plant isoprenoids production. In the current study, we describe the usage of the food grade Lactococcus lactis as a potential heterologous host for the production of sesquiterpenes from a local herbaceous Malaysian plant, Persicaria minor (synonym Polygonum minus. A sesquiterpene synthase gene from P. minor was successfully cloned and expressed in L. lactis. The expressed protein was identified to be a β-sesquiphellandrene synthase as it was demonstrated to be functional in producing β-sesquiphellandrene at 85.4% of the total sesquiterpenes produced based on in vitro enzymatic assays. The recombinant L. lactis strain developed in this study was also capable of producing β-sesquiphellandrene in vivo without exogenous substrates supplementation. In addition, overexpression of the strain's endogenous 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGR, an established rate-limiting enzyme in the eukaryotic mevalonate pathway, increased the production level of β-sesquiphellandrene by 1.25-1.60 fold. The highest amount achieved was 33 nM at 2 h post-induction.

  19. [The isozymes of stearil-coenzymeA-desaturase and insulin activity in the light of phylogenetic theory of pathology. Oleic fatty acid and realization of biologic functions of trophology and locomotion].

    Science.gov (United States)

    2013-11-01

    The formation of function of isozymes of stearil-coenzymeA-desaturases occured at the different stages of phylogeny under realization of biologic function of trophology (stearil-coenzymeA-desaturase 1) and biologic function of locomotion, insulin system (stearil-coenzymeA-desaturase 2) billions years later. The stearil-coenzymeA-desaturase 1 transforms in C 18:1 oleic fatty acid only exogenous C 16:0 palmitinic saturated fatty acid. The stearil-coenzymeA-desaturase 2 transforms only endogenic palmitinic saturated fatty acid, synthesized form glucose. The biologic role of insulin is in energy support of biologic function of locomotion. Insulin through expressing stearil-coenzymeA-desaturase 2 transforms energetically non-optimal palmitinic variation of metabolism of substrates into highly effective oleic variation for cells' groundwork of energy (saturated fatty acid and mono fatty acid). The surplus of palmitinic saturated fatty acid in food is enabled in pathogenesis of resistance to insulin and derangement of synthesis of hormone by beta-cells of islets. The resistance to insulin and diabetes mellitus are primarily the derangement of metabolism of saturated fatty acids with mono fatty acids, energy problems of organism and only afterwards the derangement of metabolism of carbohydrates. It is desirable to restrict food intake of exogenous palmitinic saturated fatty acid. The reasons are low expression of independent of insulin stearil-coenzymeA-desaturase 2, marked lipotoxicity of polar form of palmitinic saturated fatty acid and synthesis of non-optimal palmitinic triglycerides instead of physiologic and more energetically more effective oleic triglycerides.

  20. Posttranslational modification of Klebsiella pneumoniae flavodoxin by covalent attachment of coenzyme A, shown by sup 31 P NMR and electrospray mass spectrometry, prevents electron transfer from the nifJ protein to nitrogenase. A possible new regulatory mechanism for biological nitrogen fixation

    Energy Technology Data Exchange (ETDEWEB)

    Thorneley, R.N.F.; Ashby, G.A.; Drummond, M.H.; Eady, R.R.; Huff, S.; Macdonald, C.J. (Univ. of Sussex, Brighton (United Kingdom)); Abell, C.; Schneier, A. (Univ. Chemical Lab., Cambridge (United Kingdom))

    1992-02-04

    A strain of Escherichia coli (71-18) that produces ca. 15% of its soluble cytoplasmic protein as a flavodoxin, the Klebsiella pneumoniae nifF gene product, has been constructed. The flavodoxin was purified using FPLC and resolved into two forms, designated KpFldI and KpFldII, which were shown to have identical N-terminal amino acid sequences (30 residues) in agreement with that predicted by the K. pneumoniae nifF DNA sequence. {sup 31}P NMR, electrospray mass spectrometry, UV-visible spectra, and thiol group estimations showed that the single cysteine residue (position 68) of KpFldI is posttranslationally modified in KpFldII by the covalent, mixed disulfide, attachment of coenzyme A. KpFldII was inactive as an electron carrier between the K. pneumoniae nifJ product (a pyruvate-flavodoxin oxidoreductase) and K. pneumoniae nifH product (the Fe-protein of nitrogenase). This novel posttranslational modification of a flavodoxin is discussed in terms of the regulation of nitrogenase activity in vivo in response to the level of dissolved O{sub 2} and the carbon status of diazotrophic cultures.

  1. Novel solid self-emulsifying drug delivery system of coenzyme Q₁₀ with improved photochemical and pharmacokinetic behaviors.

    Science.gov (United States)

    Onoue, Satomi; Uchida, Atushi; Kuriyama, Kazuki; Nakamura, Tatsuya; Seto, Yoshiki; Kato, Masashi; Hatanaka, Junya; Tanaka, Toshiyuki; Miyoshi, Hiroyuki; Yamada, Shizuo

    2012-08-15

    The present study was undertaken to develop a solid self-emulsifying drug delivery system of coenzyme Q(10) (CoQ(10)/s-SEDDS) with high photostability and oral bioavailability. The CoQ(10)/s-SEDDS was prepared by spray-drying an emulsion preconcentrate containing CoQ(10), medium-chain triglyceride, sucrose ester of fatty acid, and hydroxypropyl cellulose, and its physicochemical, photochemical, and pharmacokinetic properties were evaluated. The CoQ(10)/s-SEDDS powder with a diameter of ca. 15 μm was obtained by spray-drying, in which the CoQ(10) was mostly amorphized. The CoQ(10)/s-SEDDS exhibited immediate self-emulsification when introduced to aqueous media under gentle agitation, forming uniform fine droplets with a mean diameter of ca. 280 nm. There was marked generation of reactive oxygen species, in particular superoxide, from CoQ(10) exposed to simulated sunlight (250W/m(2)), suggesting potent photoreactivity. Nano-emulsified solution of CoQ(10) under light exposure underwent photodegradation with 22-fold higher degradation kinetics than crystalline CoQ(10), although the CoQ(10)/s-SEDDS was less photoreactive. After the oral administration of CoQ(10)/s-SEDDS (100 mg-CoQ(10)/kg) in rats, enhanced exposure of CoQ(10) was observed with increases in both C(max) and AUC of ca. 5-fold in comparison with those of orally administered crystalline CoQ(10). From the improved physicochemical and pharmacokinetic data, the s-SEDDS approach upon spray-drying might be a suitable dosage option for enhancing nutraceutical and pharmaceutical values of CoQ(10). Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Prophylactic role of combined treatment with coenzyme Q10 and vitamin E against radiation injury in male rats

    International Nuclear Information System (INIS)

    Hussien, E.M.; Darwish, M.M.; Ali, S.E.

    2007-01-01

    The present work aims at investigating effects of whole body gamma irradiation of male albino rats at successive fractionated dose levels up to 8 Gy and the possible protection or curative control of these effects through the oral administration of Coenzyme Q10 (Co Q10) (200 mg/ kg body wt) and vitamin E (100 mg/ kg body wt) injected i.p 24 h before exposure of animals to each increment of gamma irradiation. The parameters of the study have been combined haematological values, including evaluation of different blood cells, erythrocyte counts (RBC), haemoglobin concentration (Hb), haematocrit percentage (Ht) and leucocyte counts (WBC), as well as certain serum biochemical parameters including transaminases AST and ALT) and alkaline phosphatase (ALP) activities known to be related to liver functional status. Besides body and particular organs, wt as well as serum Na + and K + levels have been also evaluated. The results obtained confirmed in general, significant decrease in whole body and organs wt, haematological disorders in form of lowering of RBC, WBC, Hb and Ht, as well as elevated AST, ALT and ALP activities in irradiated rats in both studied time intervals. A significant increase in the level of K + associated with a decrease in the level of Na + was also recorded in the serum of irradiated rats. As simultaneous administration of Co Q10 and vitamin E prior to irradiation prevented pathological changes of analyzed parameters, the results of this study confirmed efficient protection with use of these antioxidants against the health hazards induced by gamma radiation exposure

  3. Genetic Rescue of Mitochondrial and Skeletal Muscle Impairment in an Induced Pluripotent Stem Cells Model of Coenzyme Q10 Deficiency.

    Science.gov (United States)

    Romero-Moya, Damià; Santos-Ocaña, Carlos; Castaño, Julio; Garrabou, Gloria; Rodríguez-Gómez, José A; Ruiz-Bonilla, Vanesa; Bueno, Clara; González-Rodríguez, Patricia; Giorgetti, Alessandra; Perdiguero, Eusebio; Prieto, Cristina; Moren-Nuñez, Constanza; Fernández-Ayala, Daniel J; Victoria Cascajo, Maria; Velasco, Iván; Canals, Josep Maria; Montero, Raquel; Yubero, Delia; Jou, Cristina; López-Barneo, José; Cardellach, Francesc; Muñoz-Cánoves, Pura; Artuch, Rafael; Navas, Plácido; Menendez, Pablo

    2017-07-01

    Coenzyme Q 10 (CoQ 10 ) plays a crucial role in mitochondria as an electron carrier within the mitochondrial respiratory chain (MRC) and is an essential antioxidant. Mutations in genes responsible for CoQ 10 biosynthesis (COQ genes) cause primary CoQ 10 deficiency, a rare and heterogeneous mitochondrial disorder with no clear genotype-phenotype association, mainly affecting tissues with high-energy demand including brain and skeletal muscle (SkM). Here, we report a four-year-old girl diagnosed with minor mental retardation and lethal rhabdomyolysis harboring a heterozygous mutation (c.483G > C (E161D)) in COQ4. The patient's fibroblasts showed a decrease in [CoQ 10 ], CoQ 10 biosynthesis, MRC activity affecting complexes I/II + III, and respiration defects. Bona fide induced pluripotent stem cell (iPSCs) lines carrying the COQ4 mutation (CQ4-iPSCs) were generated, characterized and genetically edited using the CRISPR-Cas9 system (CQ4 ed -iPSCs). Extensive differentiation and metabolic assays of control-iPSCs, CQ4-iPSCs and CQ4 ed -iPSCs demonstrated a genotype association, reproducing the disease phenotype. The COQ4 mutation in iPSC was associated with CoQ 10 deficiency, metabolic dysfunction, and respiration defects. iPSC differentiation into SkM was compromised, and the resulting SkM also displayed respiration defects. Remarkably, iPSC differentiation in dopaminergic or motor neurons was unaffected. This study offers an unprecedented iPSC model recapitulating CoQ 10 deficiency-associated functional and metabolic phenotypes caused by COQ4 mutation. Stem Cells 2017;35:1687-1703. © 2017 AlphaMed Press.

  4. Beneficial effects of co-enzyme Q10 and rosiglitazone in fructose-induced metabolic syndrome in rats

    Directory of Open Access Journals (Sweden)

    Suzan M. Mansour

    2013-06-01

    Full Text Available Increased fructose consumption is strongly associated with metabolic syndrome (MS. This study was performed to elucidate the role of co-enzyme Q10 (CoQ and/or rosiglitazone (Rosi in fructose induced MS. Four groups of rats (n = 8–10 were fed on fructose-enriched diet (FED for 16 weeks. One served as FED-control while the remaining groups were treated with CoQ (10 mg/kg/day, Rosi (4 mg/kg/day or their combination during the last 6 weeks. Another group was fed on normal laboratory chow (normal control. At the end of the experiment, blood samples were collected for estimation of markers related to MS. In addition, histological examination of liver, kidney and pancreas samples was done. Induction of the MS was associated with increased body weight gain (34% coupled with elevated levels of blood glucose (48%, insulin (86%, insulin resistance (270%, uric acid (69%, urea (155%, creatinine (129% and blood lipids with different degrees. Fructose-induced MS also reduced plasma catalase (62% and glutathione peroxidase (89% activities parallel to increased serum leptin and tumor necrosis factor-alpha (TNF-α levels. These changes were coupled by marked histological changes in the examined tissues. Treatment with CoQ or Rosi attenuated most of MS-induced changes. Besides, the combination of both agents further reduced blood glucose, total cholesterol, triglycerides and urea levels, as well as, normalized serum levels of leptin and TNF-α. In addition, combined therapy of both agents elevated HDL-cholesterol level and glutathione peroxidase activity. In conclusion, the present study proves the benefits of co-supplementation of CoQ and Rosi in a fructose-induced model of insulin resistance.

  5. Characterization of Benzoyl Coenzyme A Biosynthesis Genes in the Enterocin-Producing Bacterium “Streptomyces maritimus”

    Science.gov (United States)

    Xiang, Longkuan; Moore, Bradley S.

    2003-01-01

    The novel benzoyl coenzyme A (benzoyl-CoA) biosynthesis pathway in “Streptomyces maritimus” was investigated through a series of target-directed mutations. Genes involved in benzoyl-CoA formation were disrupted through single-crossover homologous recombination, and the resulting mutants were analyzed for their ability to biosynthesize the benzoyl-CoA-primed polyketide antibiotic enterocin. Inactivation of the unique phenylalanine ammonia-lyase-encoding gene encP was previously shown to be absolutely required for benzoyl-CoA formation in “S. maritimus”. The fatty acid β-oxidation-related genes encH, -I, and -J, on the other hand, are necessary but not required. In each case, the yield of benzoyl-CoA-primed enterocin dropped below wild-type levels. We attribute the reduced benzoyl-CoA formation in these specific mutants to functional substitution and cross-talk between the products of genes encH, -I, and -J and the enzyme homologues of primary metabolism. Disruption of the benzoate-CoA ligase encN gene did not perturb enterocin production, however, demonstrating that encN is extraneous and that benzoic acid is not a pathway intermediate. EncN rather serves as a substitute pathway for utilizing exogenous benzoic acid. These experiments provide further support that benzoyl-CoA is formed in a novel bacterial pathway that resembles the eukaryotic assembly of benzoyl-CoA from phenylalanine via a β-oxidative path. PMID:12511484

  6. Role of Feedback Regulation of Pantothenate Kinase (CoaA) in Control of Coenzyme A Levels in Escherichia coli

    Science.gov (United States)

    Rock, Charles O.; Park, Hee-Won; Jackowski, Suzanne

    2003-01-01

    Pantothenate kinase (CoaA) is a key regulator of coenzyme A (CoA) biosynthesis in Escherichia coli, and its activity is controlled by feedback inhibition by CoA and its thioesters. The importance of feedback inhibition in the control of the intracellular CoA levels was tested by constructing three site-directed mutants of CoaA that were predicted to be feedback resistant based on the crystal structure of the CoaA-CoA binary complex. CoaA[R106A], CoaA[H177Q], and CoaA[F247V] were purified and shown to retain significant catalytic activity and be refractory to inhibition by CoA. CoaA[R106A] retained 50% of the catalytic activity of CoaA, whereas the CoaA[H177Q] and CoaA[F247V] mutants were less active. The importance of feedback control of CoaA to the intracellular CoA levels was assessed by expressing either CoaA or CoaA[R106A] in strain ANS3 [coaA15(Ts) panD2]. Cells expressing CoaA[R106A] had significantly higher levels of phosphorylated pantothenate-derived metabolites and CoA in vivo and excreted significantly more 4′-phosphopantetheine into the medium compared to cells expressing the wild-type protein. These data illustrate the key role of feedback regulation of pantothenate kinase in the control of intracellular CoA levels. PMID:12754240

  7. Regulation of the oxidative balance with coenzyme Q10 sensitizes human glioblastoma cells to radiation and temozolomide.

    Science.gov (United States)

    Frontiñán-Rubio, Javier; Santiago-Mora, Raquel María; Nieva-Velasco, Consuelo María; Ferrín, Gustavo; Martínez-González, Alicia; Gómez, María Victoria; Moreno, María; Ariza, Julia; Lozano, Eva; Arjona-Gutiérrez, Jacinto; Gil-Agudo, Antonio; De la Mata, Manuel; Pesic, Milica; Peinado, Juan Ramón; Villalba, José M; Pérez-Romasanta, Luis; Pérez-García, Víctor M; Alcaín, Francisco J; Durán-Prado, Mario

    2018-05-18

    To investigate how the modulation of the oxidative balance affects cytotoxic therapies in glioblastoma, in vitro. Human glioblastoma U251 and T98 cells and normal astrocytes C8D1A were loaded with coenzyme Q10 (CoQ). Mitochondrial superoxide ion (O 2 - ) and H 2 O 2 were measured by fluorescence microscopy. OXPHOS performance was assessed in U251 cells with an oxytherm Clark-type electrode. Radio- and chemotherapy cytotoxicity was assessed by immunostaining of γH2AX (24 h), annexin V and nuclei morphology, at short (72 h) and long (15 d) time. Hif-1α, SOD1, SOD2 and NQO1 were determined by immunolabeling. Catalase activity was measured by classic enzymatic assay. Glutathione levels and total antioxidant capacity were quantified using commercial kits. CoQ did not affect oxygen consumption but reduced the level of O 2 - and H 2 O 2 while shifted to a pro-oxidant cell status mainly due to a decrease in catalase activity and SOD2 level. Hif-1α was dampened, echoed by a decrease lactate and several key metabolites involved in glutathione synthesis. CoQ-treated cells were twofold more sensitive than control to radiation-induced DNA damage and apoptosis in short and long-term clonogenic assays, potentiating TMZ-induced cytotoxicity, without affecting non-transformed astrocytes. CoQ acts as sensitizer for cytotoxic therapies, disarming GBM cells, but not normal astrocytes, against further pro-oxidant injuries, being potentially useful in clinical practice for this fatal pathology. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency.

    Science.gov (United States)

    Lagier-Tourenne, Clotilde; Tazir, Meriem; López, Luis Carlos; Quinzii, Catarina M; Assoum, Mirna; Drouot, Nathalie; Busso, Cleverson; Makri, Samira; Ali-Pacha, Lamia; Benhassine, Traki; Anheim, Mathieu; Lynch, David R; Thibault, Christelle; Plewniak, Frédéric; Bianchetti, Laurent; Tranchant, Christine; Poch, Olivier; DiMauro, Salvatore; Mandel, Jean-Louis; Barros, Mario H; Hirano, Michio; Koenig, Michel

    2008-03-01

    Muscle coenzyme Q(10) (CoQ(10) or ubiquinone) deficiency has been identified in more than 20 patients with presumed autosomal-recessive ataxia. However, mutations in genes required for CoQ(10) biosynthetic pathway have been identified only in patients with infantile-onset multisystemic diseases or isolated nephropathy. Our SNP-based genome-wide scan in a large consanguineous family revealed a locus for autosomal-recessive ataxia at chromosome 1q41. The causative mutation is a homozygous splice-site mutation in the aarF-domain-containing kinase 3 gene (ADCK3). Five additional mutations in ADCK3 were found in three patients with sporadic ataxia, including one known to have CoQ(10) deficiency in muscle. All of the patients have childhood-onset cerebellar ataxia with slow progression, and three of six have mildly elevated lactate levels. ADCK3 is a mitochondrial protein homologous to the yeast COQ8 and the bacterial UbiB proteins, which are required for CoQ biosynthesis. Three out of four patients tested showed a low endogenous pool of CoQ(10) in their fibroblasts or lymphoblasts, and two out of three patients showed impaired ubiquinone synthesis, strongly suggesting that ADCK3 is also involved in CoQ(10) biosynthesis. The deleterious nature of the three identified missense changes was confirmed by the introduction of them at the corresponding positions of the yeast COQ8 gene. Finally, a phylogenetic analysis shows that ADCK3 belongs to the family of atypical kinases, which includes phosphoinositide and choline kinases, suggesting that ADCK3 plays an indirect regulatory role in ubiquinone biosynthesis possibly as part of a feedback loop that regulates ATP production.

  9. Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways

    Directory of Open Access Journals (Sweden)

    Hsiao-Ya Tsai

    2016-01-01

    Full Text Available Coenzyme Q10 (CoQ10, an antiapoptosis enzyme, is stored in the mitochondria of cells. We investigated whether CoQ10 can attenuate high glucose-induced endothelial progenitor cell (EPC apoptosis and clarified its mechanism. EPCs were incubated with normal glucose (5 mM or high glucose (25 mM enviroment for 3 days, followed by treatment with CoQ10 (10 μM for 24 hr. Cell proliferation, nitric oxide (NO production, and JC-1 assay were examined. The specific signal pathways of AMP-activated protein kinase (AMPK, eNOS/Akt, and heme oxygenase-1 (HO-1 were also assessed. High glucose reduced EPC functional activities, including proliferation and migration. Additionally, Akt/eNOS activity and NO production were downregulated in high glucose-stimulated EPCs. Administration of CoQ10 ameliorated high glucose-induced EPC apoptosis, including downregulation of caspase 3, upregulation of Bcl-2, and increase in mitochondrial membrane potential. Furthermore, treatment with CoQ10 reduced reactive oxygen species, enhanced eNOS/Akt activity, and increased HO-1 expression in high glucose-treated EPCs. These effects were negated by administration of AMPK inhibitor. Transplantation of CoQ10-treated EPCs under high glucose conditions into ischemic hindlimbs improved blood flow recovery. CoQ10 reduced high glucose-induced EPC apoptosis and dysfunction through upregulation of eNOS, HO-1 through the AMPK pathway. Our findings provide a potential treatment strategy targeting dysfunctional EPC in diabetic patients.

  10. Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways

    Science.gov (United States)

    Tsai, Hsiao-Ya; Lin, Chih-Pei; Huang, Po-Hsun; Li, Szu-Yuan; Chen, Jia-Shiong; Lin, Feng-Yen; Chen, Jaw-Wen; Lin, Shing-Jong

    2016-01-01

    Coenzyme Q10 (CoQ10), an antiapoptosis enzyme, is stored in the mitochondria of cells. We investigated whether CoQ10 can attenuate high glucose-induced endothelial progenitor cell (EPC) apoptosis and clarified its mechanism. EPCs were incubated with normal glucose (5 mM) or high glucose (25 mM) enviroment for 3 days, followed by treatment with CoQ10 (10 μM) for 24 hr. Cell proliferation, nitric oxide (NO) production, and JC-1 assay were examined. The specific signal pathways of AMP-activated protein kinase (AMPK), eNOS/Akt, and heme oxygenase-1 (HO-1) were also assessed. High glucose reduced EPC functional activities, including proliferation and migration. Additionally, Akt/eNOS activity and NO production were downregulated in high glucose-stimulated EPCs. Administration of CoQ10 ameliorated high glucose-induced EPC apoptosis, including downregulation of caspase 3, upregulation of Bcl-2, and increase in mitochondrial membrane potential. Furthermore, treatment with CoQ10 reduced reactive oxygen species, enhanced eNOS/Akt activity, and increased HO-1 expression in high glucose-treated EPCs. These effects were negated by administration of AMPK inhibitor. Transplantation of CoQ10-treated EPCs under high glucose conditions into ischemic hindlimbs improved blood flow recovery. CoQ10 reduced high glucose-induced EPC apoptosis and dysfunction through upregulation of eNOS, HO-1 through the AMPK pathway. Our findings provide a potential treatment strategy targeting dysfunctional EPC in diabetic patients. PMID:26682233

  11. Selected biomarkers as predictive tools in testing efficacy of melatonin and coenzyme Q on propionic acid - induced neurotoxicity in rodent model of autism.

    Science.gov (United States)

    Al-Ghamdi, Mashael; Al-Ayadhi, Laila; El-Ansary, Afaf

    2014-02-25

    Exposures to environmental toxins are now thought to contribute to the development of autism spectrum disorder. Propionic acid (PA) found as a metabolic product of gut bacteria has been reported to mimic/mediate the neurotoxic effects of autism. Results from animal studies may guide investigations on human populations toward identifying environmental contaminants that produce or drugs that protect from neurotoxicity. Forty-eight young male Western Albino rats were used in the present study. They were grouped into six equal groups 8 rats each. The first group received a neurotoxic dose of buffered PA (250 mg/Kg body weight/day for 3 consecutive days). The second group received only phosphate buffered saline (control group). The third and fourth groups were intoxicated with PA as described above followed by treatment with either coenzyme Q (4.5 mg/kg body weight) or melatonin (10 mg/kg body weight) for one week (therapeutically treated groups). The fifth and sixth groups were administered both compounds for one week prior to PA (protected groups). Heat shock protein70 (Hsp70), Gamma amino-butyric acid (GABA), serotonin, dopamine, oxytocin and interferon γ-inducible protein 16 together with Comet DNA assay were measured in brain tissues of the six studied groups. The obtained data showed that PA caused multiple signs of brain toxicity revealed in depletion of GABA, serotonin, and dopamine, are which important neurotransmitters that reflect brain function, interferon γ-inducible protein 16 and oxytocin. A high significant increase in tail length, tail DNA% damage and tail moment was reported indicating the genotoxic effect of PA. Administration of melatonin or coenzyme Q showed both protective and therapeutic effects on PA-treated rats demonstrated in a remarkable amelioration of most of the measured parameters. In conclusion, melatonin and coenzyme Q have potential protective and restorative effects against PA-induced brain injury, confirmed by improvement in

  12. Synthesis of ethyl [14CH3]methylmalonyl thioglycolate as a possible substrate analogue of [14CH3]methylmalonyl coenzyme-A

    International Nuclear Information System (INIS)

    Kovacs, I.; Kovacs, Z.

    1991-01-01

    Ethyl methylmalonyl thioglycolate is a potential substrate analogue of methylmalonyl-coenzyme-A (methylmalonyl-CoA) in the investigation of propionic acid metabolism. To prove this hypothesis, the tracer ethyl [ 14 CH 3 ] methylmalonyl thioglycolate was synthesized via methyl-Meldrum's acid to carry out the biochemical examinations. The method described can also be used to synthesize [ 14 CH 3 ] methylmalonyl-CoA by transesterification of active labelled methylmalonyl thiophenyl ester. This latter intermediate is chemically stable when stored at room temperature, and the unstable [ 14 CH 3 ]methylmalonyl-CoA can be prepared in one step just preceeding the biochemical experiments. (author)

  13. Molecular Cloning and Characterization of Two Genes for the Biotin Carboxylase and Carboxyltransferase Subunits of Acetyl Coenzyme A Carboxylase in Myxococcus xanthus

    OpenAIRE

    Kimura, Yoshio; Miyake, Rina; Tokumasu, Yushi; Sato, Masayuki

    2000-01-01

    We have cloned a DNA fragment from a genomic library of Myxococcus xanthus using an oligonucleotide probe representing conserved regions of biotin carboxylase subunits of acetyl coenzyme A (acetyl-CoA) carboxylases. The fragment contained two open reading frames (ORF1 and ORF2), designated the accB and accA genes, capable of encoding a 538-amino-acid protein of 58.1 kDa and a 573-amino-acid protein of 61.5 kDa, respectively. The protein (AccA) encoded by the accA gene was strikingly similar t...

  14. The influence of the known radioprotective compounds on the metabolism of red blood cells. Pt. 1. Effect of crysteamine on the cellular level of the intermediates and coenzymes

    International Nuclear Information System (INIS)

    Chmiel, J.; Kopczynski, Z.; Rybczynska, M.

    1976-01-01

    Cysteamine added to the human blood smples in the final concentration of 6.5 x 10 -3 M, 1,9 x 10 -2 M and 3,8 x 10 -2 M exerts a significant effect on the metabolism of erythrocytes. The chromatographic determination of carbohydrate intermediates and coenzymes in red blood cells indicates that in lower concentration of the drug the rate of anaerobic metabolism of glucose is increased. Higher concentration of cysteamine (3.8 x 10 -3 M) enhances aerobic catabolism of glucose in pentose shunt. (author)

  15. Enhanced antitumor efficacy and counterfeited cardiotoxicity of combinatorial oral therapy using Doxorubicin- and Coenzyme Q10-liquid crystalline nanoparticles in comparison with intravenous Adriamycin

    DEFF Research Database (Denmark)

    Swarnakar, Nitin K; Thanki, Kaushik; Jain, Sanyog

    2014-01-01

    and strong synergism for combination at 1:10 dose ratio owing to higher cellular uptake, nuclear colocalization, higher apoptotic index and 8-OHdG levels. The prophylactic antitumor efficacy of the CoQ10-LCNPs was also established using tumor induction and progression studies. Finally, therapeutic antitumor......, with Dox-induced-cardiotoxicity was completely counterfeited in combination. In nutshell, LCNPs pose great potential in improving the therapeutic efficacy of drugs by oral route of administration. FROM THE CLINICAL EDITOR: This study describes the use of liquid crystalline nanoparticles containing coenzyme...

  16. TBscore II

    DEFF Research Database (Denmark)

    Rudolf, Frauke; Lemvik, Grethe; Abate, Ebba

    2013-01-01

    Abstract Background: The TBscore, based on simple signs and symptoms, was introduced to predict unsuccessful outcome in tuberculosis patients on treatment. A recent inter-observer variation study showed profound variation in some variables. Further, some variables depend on a physician assessing...... them, making the score less applicable. The aim of the present study was to simplify the TBscore. Methods: Inter-observer variation assessment and exploratory factor analysis were combined to develop a simplified score, the TBscore II. To validate TBscore II we assessed the association between start...

  17. Pb II

    African Journals Online (AJOL)

    Windows User

    This investigation describes the use of non-living biomass of Aspergillus caespitosus for removal of ... Pb(II) production has exceeded 3.5 million tons per year. It has been used in the ... This biomass was selected after screening a wide range of microbes. .... prolonged, which proved better biopolymer in metal uptake (Gadd ...

  18. Expression of the Acyl-Coenzyme A: Cholesterol Acyltransferase GFP Fusion Protein in Sf21 Insect Cells

    Science.gov (United States)

    Mahtani, H. K.; Richmond, R. C.; Chang, T. Y.; Chang, C. C. Y.; Rose, M. Franklin (Technical Monitor)

    2001-01-01

    The enzyme acyl-coenzyme A:cholesterol acyltransferase (ACAT) is an important contributor to the pathological expression of plaque leading to artherosclerosis n a major health problem. Adequate knowledge of the structure of this protein will enable pharmaceutical companies to design drugs specific to the enzyme. ACAT is a membrane protein located in the endoplasmic reticulum.t The protein has never been purified to homogeneity.T.Y. Chang's laboratory at Dartmouth College provided a 4-kb cDNA clone (K1) coding for a structural gene of the protein. We have modified the gene sequence and inserted the cDNA into the BioGreen His Baculovirus transfer vector. This was successfully expressed in Sf2l insect cells as a GFP-labeled ACAT protein. The advantage to this ACAT-GFP fusion protein (abbreviated GCAT) is that one can easily monitor its expression as a function of GFP excitation at 395 nm and emission at 509 nm. Moreover, the fusion protein GCAT can be detected on Western blots with the use of commercially available GFP antibodies. Antibodies against ACAT are not readily available. The presence of the 6xHis tag in the transfer vector facilitates purification of the recombinant protein since 6xHis fusion proteins bind with high affinity to Ni-NTA agarose. Obtaining highly pure protein in large quantities is essential for subsequent crystallization. The purified GCAT fusion protein can readily be cleaved into distinct GFP and ACAT proteins in the presence of thrombin. Thrombin digests the 6xHis tag linking the two protein sequences. Preliminary experiments have indicated that both GCAT and ACAT are expressed as functional proteins. The ultimate aim is to obtain large quantities of the ACAT protein in pure and functional form appropriate for protein crystal growth. Determining protein structure is the key to the design and development of effective drugs. X-ray analysis requires large homogeneous crystals that are difficult to obtain in the gravity environment of earth

  19. Five Fatty Acyl-Coenzyme A Reductases Are Involved in the Biosynthesis of Primary Alcohols in Aegilops tauschii Leaves

    Directory of Open Access Journals (Sweden)

    Meiling Wang

    2017-06-01

    Full Text Available The diploid Aegilops tauschii is the D-genome donor to hexaploid wheat (Triticum aestivum and represents a potential source for genetic study in common wheat. The ubiquitous wax covering the aerial parts of plants plays an important role in protecting plants against non-stomatal water loss. Cuticular waxes are complex mixtures of very-long-chain fatty acids, alkanes, primary and/or secondary alcohols, aldehydes, ketones, esters, triterpenes, sterols, and flavonoids. In the present work, primary alcohols were identified as the major components of leaf cuticular wax in Ae. tauschii, with C26:0-OH being the dominant primary alcohol. Analysis by scanning electron microscope revealed that dense platelet-shaped wax crystals were deposited on leaf surfaces of Ae. tauschii. Ten putative wax biosynthetic genes encoding fatty acyl-coenzyme A reductase (FAR were identified in the genome of Ae. tauschii. Five of these genes, Ae.tFAR1, Ae.tFAR2, Ae.tFAR3, Ae.tFAR4, and Ae.tFAR6, were found expressed in the leaf blades. Heterologous expression of the five Ae.tFARs in yeast (Saccharomyces cerevisiae showed that Ae.tFAR1, Ae.tFAR2, Ae.tFAR3, Ae.tFAR4, and Ae.tFAR6 were predominantly responsible for the accumulation of C16:0, C18:0, C26:0, C24:0, and C28:0 primary alcohols, respectively. In addition, nine Ae.tFAR paralogous genes were located on D chromosome of wheat and the wheat nullisomic–tetrasomic lines with the loss of Ae.tFAR3 and Ae.tFAR4 paralogous genes had significantly reduced levels of primary alcohols in the leaf blades. Collectively, these data suggest that Ae.tFAR1, Ae.tFAR2, Ae.tFAR3, Ae.tFAR4, and Ae.tFAR6 encode alcohol-forming FARs involved in the biosynthesis of primary alcohols in the leaf blades of Ae. tauschii. The information obtained in Ae. tauschii enables us to better understand wax biosynthesis in common wheat.

  20. Epoxyalkane:Coenzyme M Transferase Gene Diversity and Distribution in Groundwater Samples from Chlorinated-Ethene-Contaminated Sites

    Science.gov (United States)

    Liu, Xikun

    2016-01-01

    ABSTRACT Epoxyalkane:coenzyme M transferase (EaCoMT) plays a critical role in the aerobic biodegradation and assimilation of alkenes, including ethene, propene, and the toxic chloroethene vinyl chloride (VC). To improve our understanding of the diversity and distribution of EaCoMT genes in the environment, novel EaCoMT-specific terminal-restriction fragment length polymorphism (T-RFLP) and nested-PCR methods were developed and applied to groundwater samples from six different contaminated sites. T-RFLP analysis revealed 192 different EaCoMT T-RFs. Using clone libraries, we retrieved 139 EaCoMT gene sequences from these samples. Phylogenetic analysis revealed that a majority of the sequences (78.4%) grouped with EaCoMT genes found in VC- and ethene-assimilating Mycobacterium strains and Nocardioides sp. strain JS614. The four most-abundant T-RFs were also matched with EaCoMT clone sequences related to Mycobacterium and Nocardioides strains. The remaining EaCoMT sequences clustered within two emergent EaCoMT gene subgroups represented by sequences found in propene-assimilating Gordonia rubripertincta strain B-276 and Xanthobacter autotrophicus strain Py2. EaCoMT gene abundance was positively correlated with VC and ethene concentrations at the sites studied. IMPORTANCE The EaCoMT gene plays a critical role in assimilation of short-chain alkenes, such as ethene, VC, and propene. An improved understanding of EaCoMT gene diversity and distribution is significant to the field of bioremediation in several ways. The expansion of the EaCoMT gene database and identification of incorrectly annotated EaCoMT genes currently in the database will facilitate improved design of environmental molecular diagnostic tools and high-throughput sequencing approaches for future bioremediation studies. Our results further suggest that potentially significant aerobic VC degraders in the environment are not well represented in pure culture. Future research should aim to isolate and

  1. Sesquiterpene Synthase-3-Hydroxy-3-Methylglutaryl Coenzyme A Synthase Fusion Protein Responsible for Hirsutene Biosynthesis in Stereum hirsutum.

    Science.gov (United States)

    Flynn, Christopher M; Schmidt-Dannert, Claudia

    2018-06-01

    The wood-rotting mushroom Stereum hirsutum is a known producer of a large number of namesake hirsutenoids, many with important bioactivities. Hirsutenoids form a structurally diverse and distinct class of sesquiterpenoids. No genes involved in hirsutenoid biosynthesis have yet been identified or their enzymes characterized. Here, we describe the cloning and functional characterization of a hirsutene synthase as an unexpected fusion protein of a sesquiterpene synthase (STS) with a C-terminal 3-hydroxy-3-methylglutaryl-coenzyme A (3-hydroxy-3-methylglutaryl-CoA) synthase (HMGS) domain. Both the full-length fusion protein and truncated STS domain are highly product-specific 1,11-cyclizing STS enzymes with kinetic properties typical of STSs. Complementation studies in Saccharomyces cerevisiae confirmed that the HMGS domain is also functional in vivo Phylogenetic analysis shows that the hirsutene synthase domain does not form a clade with other previously characterized sesquiterpene synthases from Basidiomycota. Comparative gene structure analysis of this hirsutene synthase with characterized fungal enzymes reveals a significantly higher intron density, suggesting that this enzyme may be acquired by horizontal gene transfer. In contrast, the HMGS domain is clearly related to other fungal homologs. This STS-HMGS fusion protein is part of a biosynthetic gene cluster that includes P450s and oxidases that are expressed and could be cloned from cDNA. Finally, this unusual fusion of a terpene synthase to an HMGS domain, which is not generally recognized as a key regulatory enzyme of the mevalonate isoprenoid precursor pathway, led to the identification of additional HMGS duplications in many fungal genomes, including the localization of HMGSs in other predicted sesquiterpenoid biosynthetic gene clusters. IMPORTANCE Hirsutenoids represent a structurally diverse class of bioactive sesquiterpenoids isolated from fungi. Identification of their biosynthetic pathways will provide

  2. Effects of Coenzyme Q10 and Vitamin C on Growth Performance and Blood Components in Broiler Chickens under Heat Stress

    Directory of Open Access Journals (Sweden)

    Raeisi-Zeydabad S

    2017-10-01

    Full Text Available This experiment was carried out to study the effects of Coenzyme Q10 (CoQ10 and vitamin C (VC on growth performance and blood biochemistry in broiler chickens under heat stress conditions. One of three levels of CoQ10 (0, 20, and 40 mg/kg of diet and one of two levels of VC (0 and 250 mg/kg of diet were supplemented to diets of chicks (from 1-42 d of age in a 3 × 2 factorial arrangement. Each dietary treatment had four replicate pens (10 chicks/pen. In order to create chronic heat stress, the house temperature was set at an ambient temperature of 35±2°C for 8 hrs daily (09:00 to 17:00 between 25-42 d of age. Feed intake, body weight gain (BWG, and feed to gain ratio (F:G were recorded at d 10, 25 and 42. At the end of experiment, two chicks/pen were randomly selected to assess blood components. CoQ10 supplementation improved BWG and F:G during 11-25 days, 26-42 days, and the whole period of the experiment (P < 0.05, while VC supplementation improved BWG and F:G only during 11-25 d of age. Blood glucose, cholesterol and triglycerides concentrations were reduced (P < 0.05 by addition of CoQ10 to the diet. Both Supplementation of CoQ10 and VC together lowered heterophil (H count but increased lymphocyte (L count, thereby reducing H/L ratio (P < 0.05. Serum concentrations of corticosterone and T4 were positively affected by dietary supplementation of CoQ10 (P < 0.05, but no differences were obtained with addition of VC to the diet. In conclusion, our observations demonstrated that dietary supplementation of 40 mg/kg CoQ10 or 250 mg/kg VC improves the growth performance of broiler chickens under the heat stress.

  3. Role of Wax Ester Synthase/Acyl Coenzyme A:Diacylglycerol Acyltransferase in Oleaginous Streptomyces sp. Strain G25

    Science.gov (United States)

    Röttig, Annika; Strittmatter, Carl Simon; Schauer, Jennifer; Hiessl, Sebastian; Daniel, Rolf

    2016-01-01

    ABSTRACT Recently, we isolated a novel Streptomyces strain which can accumulate extraordinarily large amounts of triacylglycerol (TAG) and consists of 64% fatty acids (dry weight) when cultivated with glucose and 50% fatty acids (dry weight) when cultivated with cellobiose. To identify putative gene products responsible for lipid storage and cellobiose utilization, we analyzed its draft genome sequence. A single gene encoding a wax ester synthase/acyl coenzyme A (CoA):diacylglycerol acyltransferase (WS/DGAT) was identified and heterologously expressed in Escherichia coli. The purified enzyme AtfG25 showed acyltransferase activity with C12- or C16-acyl-CoA, C12 to C18 alcohols, or dipalmitoyl glycerol. This acyltransferase exhibits 24% amino acid identity to the model enzyme AtfA from Acinetobacter baylyi but has high sequence similarities to WS/DGATs from other Streptomyces species. To investigate the impact of AtfG25 on lipid accumulation, the respective gene, atfG25, was inactivated in Streptomyces sp. strain G25. However, cells of the insertion mutant still exhibited DGAT activity and were able to store TAG, albeit in lower quantities and at lower rates than the wild-type strain. These findings clearly indicate that AtfG25 has an important, but not exclusive, role in TAG biosynthesis in the novel Streptomyces isolate and suggest the presence of alternative metabolic pathways for lipid accumulation which are discussed in the present study. IMPORTANCE A novel Streptomyces strain was isolated from desert soil, which represents an extreme environment with high temperatures, frequent drought, and nutrient scarcity. We believe that these harsh conditions promoted the development of the capacity for this strain to accumulate extraordinarily large amounts of lipids. In this study, we present the analysis of its draft genome sequence with a special focus on enzymes potentially involved in its lipid storage. Furthermore, the activity and importance of the detected

  4. Effects of coenzyme Q10 on statin-induced myopathy: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Banach, Maciej; Serban, Corina; Sahebkar, Amirhossein; Ursoniu, Sorin; Rysz, Jacek; Muntner, Paul; Toth, Peter P; Jones, Steven R; Rizzo, Manfredi; Glasser, Stephen P; Lip, Gregory Y H; Dragan, Simona; Mikhailidis, Dimitri P

    2015-01-01

    To evaluate the efficacy of coenzyme Q10 (CoQ10) supplementation on statin-induced myopathy. We searched the MEDLINE, Cochrane Library, Scopus, and EMBASE databases (November 1, 1987, to May 1, 2014) to identify randomized controlled trials investigating the impact of CoQ10 on muscle pain and plasma creatine kinase (CK) activity as 2 measures of statin-induced myalgia. Two independent reviewers extracted data on study characteristics, methods, and outcomes. We included 6 studies with 302 patients receiving statin therapy: 5 studies with 226 participants evaluated the effect of CoQ10 supplementation on plasma CK activity, and 5 studies (4 used in the CK analysis and 1 other study) with 253 participants were included to assess the effect of CoQ10 supplementation on muscle pain. Compared with the control group, plasma CK activity was increased after CoQ10 supplementation, but this change was not significant (mean difference, 11.69 U/L [to convert to μkat/L, multiply by 0.0167]; 95% CI, -14.25 to 37.63 U/L; P=.38). Likewise, CoQ10 supplementation had no significant effect on muscle pain despite a trend toward a decrease (standardized mean difference, -0.53; 95% CI, -1.33 to 0.28; P=.20). No dose-effect association between changes in plasma CK activity (slope, -0.001; 95% CI, -0.004 to 0.001; P=.33) or in the indices of muscle pain (slope, 0.002; 95% CI, -0.005 to 0.010; P=.67) and administered doses of CoQ10 were observed. The results of this meta-analysis of available randomized controlled trials do not suggest any significant benefit of CoQ10 supplementation in improving statin-induced myopathy. Larger, well-designed trials are necessary to confirm the findings from this meta-analysis. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  5. Effect of Polyhydroxybutyrate (PHB) storage on L-arginine production in recombinant Corynebacterium crenatum using coenzyme regulation.

    Science.gov (United States)

    Xu, Meijuan; Qin, Jingru; Rao, Zhiming; You, Hengyi; Zhang, Xian; Yang, Taowei; Wang, Xiaoyuan; Xu, Zhenghong

    2016-01-19

    Corynebacterium crenatum SYPA 5 is the industrial strain for L-arginine production. Poly-β-hydroxybutyrate (PHB) is a kind of biopolymer stored as bacterial reserve materials for carbon and energy. The introduction of the PHB synthesis pathway into several strains can regulate the global metabolic pathway. In addition, both the pathways of PHB and L-arginine biosynthesis in the cells are NADPH-dependent. NAD kinase could upregulate the NADPH concentration in the bacteria. Thus, it is interesting to investigate how both PHB and NAD kinase affect the L-arginine biosynthesis in C. crenatum SYPA 5. C. crenatum P1 containing PHB synthesis pathway was constructed and cultivated in batch fermentation for 96 h. The enzyme activities of the key enzymes were enhanced comparing to the control strain C. crenatum SYPA 5. More PHB was found in C. crenatum P1, up to 12.7 % of the dry cell weight. Higher growth level and enhanced glucose consumptions were also observed in C. crenatum P1. With respect to the yield of L-arginine, it was 38.54 ± 0.81 g/L, increasing by 20.6 %, comparing to the control under the influence of PHB accumulation. For more NADPH supply, C. crenatum P2 was constructed with overexpression of NAD kinase based on C. crenatum P1. The NADPH concentration was increased in C. crenatum P2 comparing to the control. PHB content reached 15.7 % and 41.11 ± 1.21 g/L L-arginine was obtained in C. crenatum P2, increased by 28.6 %. The transcription levels of key L-arginine synthesis genes, argB, argC, argD and argJ in recombinant C. crenatum increased 1.9-3.0 times compared with the parent strain. Accumulation of PHB by introducing PHB synthesis pathway, together with up-regulation of coenzyme level by overexpressing NAD kinase, enables the recombinant C. crenatum to serve as high-efficiency cell factories in the long-time L-arginine fermentation. Furthermore, batch cultivation of the engineered C. crenatum revealed that it could accumulate both extracellular L

  6. TetR Family Transcriptional Regulator PccD Negatively Controls Propionyl Coenzyme A Assimilation in Saccharopolyspora erythraea.

    Science.gov (United States)

    Xu, Zhen; Wang, Miaomiao; Ye, Bang-Ce

    2017-10-15

    Propanol stimulates erythromycin biosynthesis by increasing the supply of propionyl coenzyme A (propionyl-CoA), a starter unit of erythromycin production in Saccharopolyspora erythraea Propionyl-CoA is assimilated via propionyl-CoA carboxylase to methylmalonyl-CoA, an extender unit of erythromycin. We found that the addition of n -propanol or propionate caused a 4- to 16-fold increase in the transcriptional levels of the SACE_3398-3400 locus encoding propionyl-CoA carboxylase, a key enzyme in propionate metabolism. The regulator PccD was proved to be directly involved in the transcription regulation of the SACE_3398-3400 locus by EMSA and DNase I footprint analysis. The transcriptional levels of SACE_3398-3400 were upregulated 15- to 37-fold in the pccD gene deletion strain (Δ pccD ) and downregulated 3-fold in the pccD overexpression strain (WT/pIB- pccD ), indicating that PccD was a negative transcriptional regulator of SACE_3398-3400. The Δ pccD strain has a higher growth rate than that of the wild-type strain (WT) on Evans medium with propionate as the sole carbon source, whereas the growth of the WT/pIB- pccD strain was repressed. As a possible metabolite of propionate metabolism, methylmalonic acid was identified as an effector molecule of PccD and repressed its regulatory activity. A higher level of erythromycin in the Δ pccD strain was observed compared with that in the wild-type strain. Our study reveals a regulatory mechanism in propionate metabolism and suggests new possibilities for designing metabolic engineering to increase erythromycin yield. IMPORTANCE Our work has identified the novel regulator PccD that controls the expression of the gene for propionyl-CoA carboxylase, a key enzyme in propionyl-CoA assimilation in S. erythraea PccD represses the generation of methylmalonyl-CoA through carboxylation of propionyl-CoA and reveals an effect on biosynthesis of erythromycin. This finding provides novel insight into propionyl-CoA assimilation, and

  7. Systematic Analysis of the 4-Coumarate:Coenzyme A Ligase (4CL Related Genes and Expression Profiling during Fruit Development in the Chinese Pear

    Directory of Open Access Journals (Sweden)

    Yunpeng Cao

    2016-10-01

    Full Text Available In plants, 4-coumarate:coenzyme A ligases (4CLs, comprising some of the adenylate-forming enzymes, are key enzymes involved in regulating lignin metabolism and the biosynthesis of flavonoids and other secondary metabolites. Although several 4CL-related proteins were shown to play roles in secondary metabolism, no comprehensive study on 4CL-related genes in the pear and other Rosaceae species has been reported. In this study, we identified 4CL-related genes in the apple, peach, yangmei, and pear genomes using DNATOOLS software and inferred their evolutionary relationships using phylogenetic analysis, collinearity analysis, conserved motif analysis, and structure analysis. A total of 149 4CL-related genes in four Rosaceous species (pear, apple, peach, and yangmei were identified, with 30 members in the pear. We explored the functions of several 4CL and acyl-coenzyme A synthetase (ACS genes during the development of pear fruit by quantitative real-time PCR (qRT-PCR. We found that duplication events had occurred in the 30 4CL-related genes in the pear. These duplicated 4CL-related genes are distributed unevenly across all pear chromosomes except chromosomes 4, 8, 11, and 12. The results of this study provide a basis for further investigation of both the functions and evolutionary history of 4CL-related genes.

  8. An Examination by Site-Directed Mutagenesis of Putative Key Residues in the Determination of Coenzyme Specificity in Clostridial NAD+-Dependent Glutamate Dehydrogenase

    Directory of Open Access Journals (Sweden)

    Joanna Griffin

    2011-01-01

    Full Text Available Sequence and structure comparisons of various glutamate dehydrogenases (GDH and other nicotinamide nucleotide-dependent dehydrogenases have potentially implicated certain residues in coenzyme binding and discrimination. We have mutated key residues in Clostridium symbiosum NAD+-specific GDH to investigate their contribution to specificity and to enhance acceptance of NADPH. Comparisons with E. coli NADPH-dependent GDH prompted design of mutants F238S, P262S, and F238S/P262S, which were purified and assessed at pH 6.0, 7.0, and 8.0. They showed markedly increased catalytic efficiency with NADPH, especially at pH 8.0 (∼170-fold for P262S and F238S/P262S with relatively small changes for NADH. A positive charge introduced through the D263K mutation also greatly increased catalytic efficiency with NADPH (over 100-fold at pH 8 and slightly decreased activity with NADH. At position 242, “P6” of the “core fingerprint,” where NAD+- and NADP+-dependent enzymes normally have Gly or Ala, respectively, clostridial GDH already has Ala. Replacement with Gly produced negligible shift in coenzyme specificity.

  9. Sunflower Oil but Not Fish Oil Resembles Positive Effects of Virgin Olive Oil on Aged Pancreas after Life-Long Coenzyme Q Addition

    Science.gov (United States)

    González-Alonso, Adrián; Ramírez-Tortosa, César L.; Varela-López, Alfonso; Roche, Enrique; Arribas, María I.; Ramírez-Tortosa, M. Carmen; Giampieri, Francesca; Ochoa, Julio J.; Quiles, José L.

    2015-01-01

    An adequate pancreatic structure is necessary for optimal organ function. Structural changes are critical in the development of age-related pancreatic disorders. In this context, it has been reported that different pancreatic compartments from rats were affected according to the fat composition consumed. Since there is a close relationship between mitochondria, oxidative stress and aging, an experimental approach has been developed to gain more insight into this process in the pancreas. A low dosage of coenzyme Q was administered life-long in rats in order to try to prevent pancreatic aging-related alterations associated to some dietary fat sources. According to that, three groups of rats were fed normocaloric diets containing Coenzyme Q (CoQ) for two years, where virgin olive, sunflower, or fish oil was included as unique fat source. Pancreatic samples for microscopy and blood samples were collected at the moment of euthanasia. The main finding is that CoQ supplementation gives different results according to fat used in diet. When sunflower oil was the main fat in the diet, CoQ supplementation seems to improve endocrine pancreas structure and in particular β-cell mass resembling positive effects of virgin olive oil. Conversely, CoQ intake does not seem to improve the structural alterations of exocrine compartment previously observed in fish oil fed rats. Therefore CoQ may improve pancreatic alterations associated to the chronic intake of some dietary fat sources. PMID:26426013

  10. Purification of a jojoba embryo fatty acyl-coenzyme A reductase and expression of its cDNA in high erucic acid rapeseed.

    Science.gov (United States)

    Metz, J G; Pollard, M R; Anderson, L; Hayes, T R; Lassner, M W

    2000-03-01

    The jojoba (Simmondsia chinensis) plant produces esters of long-chain alcohols and fatty acids (waxes) as a seed lipid energy reserve. This is in contrast to the triglycerides found in seeds of other plants. We purified an alcohol-forming fatty acyl-coenzyme A reductase (FAR) from developing embryos and cloned the cDNA encoding the enzyme. Expression of a cDNA in Escherichia coli confers FAR activity upon those cells and results in the accumulation of fatty alcohols. The FAR sequence shows significant homology to an Arabidopsis protein of unknown function that is essential for pollen development. When the jojoba FAR cDNA is expressed in embryos of Brassica napus, long-chain alcohols can be detected in transmethylated seed oils. Resynthesis of the gene to reduce its A plus T content resulted in increased levels of alcohol production. In addition to free alcohols, novel wax esters were detected in the transgenic seed oils. In vitro assays revealed that B. napus embryos have an endogenous fatty acyl-coenzyme A: fatty alcohol acyl-transferase activity that could account for this wax synthesis. Thus, introduction of a single cDNA into B. napus results in a redirection of a portion of seed oil synthesis from triglycerides to waxes.

  11. Improved Xylitol Production from D-Arabitol by Enhancing the Coenzyme Regeneration Efficiency of the Pentose Phosphate Pathway in Gluconobacter oxydans.

    Science.gov (United States)

    Li, Sha; Zhang, Jinliang; Xu, Hong; Feng, Xiaohai

    2016-02-10

    Gluconobacter oxydans is used to produce xylitol from D-arabitol. This study aims to improve xylitol production by increasing the coenzyme regeneration efficiency of the pentose phosphate pathway in G. oxydans. Glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) were overexpressed in G. oxydans. Real-time PCR and enzyme activity assays revealed that G6PDH/6PGDH activity and coenzyme regeneration efficiency increased in the recombinant G. oxydans strains. Approximately 29.3 g/L xylitol was obtained, with a yield of 73.2%, from 40 g/L d-arabitol in the batch biotransformation with the G. oxydans PZ strain. Moreover, the xylitol productivity (0.62 g/L/h) was 3.26-fold of the wild type strain (0.19 g/L/h). In repetitive batch biotransformation, the G. oxydans PZ cells were used for five cycles without incurring a significant loss in productivity. These results indicate that the recombinant G. oxydans PZ strain is economically feasible for xylitol production in industrial bioconversion.

  12. Sunflower Oil but Not Fish Oil Resembles Positive Effects of Virgin Olive Oil on Aged Pancreas after Life-Long Coenzyme Q Addition

    Directory of Open Access Journals (Sweden)

    Adrián González-Alonso

    2015-09-01

    Full Text Available An adequate pancreatic structure is necessary for optimal organ function. Structural changes are critical in the development of age-related pancreatic disorders. In this context, it has been reported that different pancreatic compartments from rats were affected according to the fat composition consumed. Since there is a close relationship between mitochondria, oxidative stress and aging, an experimental approach has been developed to gain more insight into this process in the pancreas. A low dosage of coenzyme Q was administered life-long in rats in order to try to prevent pancreatic aging-related alterations associated to some dietary fat sources. According to that, three groups of rats were fed normocaloric diets containing Coenzyme Q (CoQ for two years, where virgin olive, sunflower, or fish oil was included as unique fat source. Pancreatic samples for microscopy and blood samples were collected at the moment of euthanasia. The main finding is that CoQ supplementation gives different results according to fat used in diet. When sunflower oil was the main fat in the diet, CoQ supplementation seems to improve endocrine pancreas structure and in particular β-cell mass resembling positive effects of virgin olive oil. Conversely, CoQ intake does not seem to improve the structural alterations of exocrine compartment previously observed in fish oil fed rats. Therefore CoQ may improve pancreatic alterations associated to the chronic intake of some dietary fat sources.

  13. Microbial products II

    Energy Technology Data Exchange (ETDEWEB)

    Pape, H; Rehm, H J [eds.

    1986-01-01

    The present volume deals mainly with compounds which have been detected as natural microbial products. Part 1 of this volume introduces the general aspects of the overproduction of metabolites and the concepts and genetics of secondary metabolism. Compounds such as nucleosides, nucleotides, coenzymes, vitamins and lipids are dealt with in part 2. Part 3 then is devoted to products and antibiotics with uses im medicine, veterinary medicine, plant protection and metabolites with antitumor activity. Several secondary metabolites have found uses in human and animal health care. With 244 figs., 109 tabs.

  14. FORMATION OF BINARY COMPLEXES OF Co(II), Ni(II) AND Cu(II ...

    African Journals Online (AJOL)

    Preferred Customer

    adverse effects and decreasing the availability of dopamine to the CNS; so it is the ... Cobalt is essential for the production of red blood cells and cobalamin and it acts as the substrate for the final enzymatic reaction that yields the active coenzyme ..... competition between hydrogen and metal ion for this second donor site.

  15. Coenzyme Q10 (PDQ)

    Science.gov (United States)

    ... NIH). NIH is the federal government’s center of biomedical research. The PDQ summaries are based on an independent ... NCCIH) are sponsoring a number of clinical trials (research studies) at medical centers to test CAM therapies for use in cancer. Conventional approaches to cancer ...

  16. Fatal hepatic short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase deficiency: clinical, biochemical, and pathological studies on three subjects with this recently identified disorder of mitochondrial beta-oxidation

    NARCIS (Netherlands)

    Bennett, M. J.; Spotswood, S. D.; Ross, K. F.; Comfort, S.; Koonce, R.; Boriack, R. L.; IJlst, L.; Wanders, R. J.

    1999-01-01

    This report describes the clinical, biochemical, and pathological findings in three infants with hepatic short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase (SCHAD) deficiency, a recently recognized disorder of the mitochondrial oxidation of straight-chain fatty acids. Candidate subjects were

  17. Small Diameter Bomb Increment II (SDB II)

    Science.gov (United States)

    2015-12-01

    Selected Acquisition Report (SAR) RCS: DD-A&T(Q&A)823-439 Small Diameter Bomb Increment II (SDB II) As of FY 2017 President’s Budget Defense... Bomb Increment II (SDB II) DoD Component Air Force Joint Participants Department of the Navy Responsible Office References SAR Baseline (Production...Mission and Description Small Diameter Bomb Increment II (SDB II) is a joint interest United States Air Force (USAF) and Department of the Navy

  18. Effects of direct-to-consumer advertising of hydroxymethylglutaryl coenzyme a reductase inhibitors on attainment of LDL-C goals.

    Science.gov (United States)

    Bradford, W David; Kleit, Andrew N; Nietert, Paul J; Ornstein, Steven

    2006-12-01

    Although highly controversial, directto-consumer (DTC) television advertising for prescription drugs is an established practice in the US health care industry. While the US Food and Drug Administration is currently reexamining its regulatory stance, little evidence exists regarding the impact of DTC advertising on patient health outcomes. The objective of this research was to study the relationship between heavy television promotion of 3 major hydroxymethylglutaryl coenzyme A reductase inhibitors ("statins") and the frequency with which patients are able to attain low-density lipoprotein cholesterol (LDL-C) blood-level goals after treatment with any statin. We used logistic regression to determine achievement of LDL-C goals at 6 months after statin treatment, using electronic medical record extract data from patients from geographically dispersed primary care practices in the United States. We identified LDL-C blood levels as being at or less than goal, as defined by risk-adjusted guidelines published by the National Heart, Lung, and Blood Institute from the Adult Treatment Panel III (ATP III) data. A total of 50,741 patients, identified from 88 practices, were diagnosed with hyperlipidemia and had begun therapy with any statin medication during the 1998-2004 time period. In addition, total dollars spent each month on television advertising at the national and local levels for atorvastatin, pravastatin, and simvastatin were obtained. DTC advertising data were merged by local media market where the physician practice was located and by the month in which the patient was first prescribed a statin. The models were run for all patients who initiated therapy, and also on a subsample of patients who continued to receive prescriptions for the drugs for at least 6 months. Logistic regressions were used to predict the likelihood that each patient attained the ATP III LDL-C blood-level goals as a function of DTC advertising and other factors. High levels of national DTC

  19. Alcohol depletes coenzyme-Q10 associated with increased TNF-alpha secretion to induce cytotoxicity in HepG2 cells

    International Nuclear Information System (INIS)

    Vidyashankar, Satyakumar; Nandakumar, Krishna S.; Patki, Pralhad S.

    2012-01-01

    Highlights: ► Ethanol induced cytotoxicity in HepG2 cells in absence of lipogenesis. ► Ethanol inhibited HMG-CoA reductase activity. ► Ethanol induced HMG-CoA reductase inhibition is due to decreased cell viability. ► Incubation with mevalonate could not increase the cholesterol. ► Cytotoxicity brought about by CoQ10 depletion and increased TNF-alpha. -- Abstract: Alcohol consumption has been implicated to cause severe hepatic steatosis which is mediated by alcohol dehydrogenase (ADH) activity and CYP 450 2E1 expression. In this context, the effect of ethanol was studied for its influence on lipogenesis in HepG2 cell which is deficient of ADH and does not express CYP 450 2E1. The results showed that ethanol at 100 mM concentration caused 40% cytotoxicity at 72 h as determined by MTT assay. The incorporation of labeled [2- 14 C] acetate into triacylglycerol and phospholipid was increased by 40% and 26% respectively upon 24 h incubation, whereas incorporation of labeled [2- 14 C] acetate into cholesterol was not significantly increased. Further, ethanol inhibited HMG-CoA reductase which is a rate-limiting enzyme in the cholesterol biosynthesis. It was observed that, HMG-CoA reductase inhibition was brought about by ethanol as a consequence of decreased cell viability, since incubation of HepG2 cells with mevalonate could not increase the cholesterol content and increase the cell viability. Addition of ethanol significantly increased TNF-alpha secretion and depleted mitochondrial coenzyme-Q 10 which is detrimental for cell viability. But vitamin E (10 mM) could partially restore coenzyme-Q 10 and glutathione content with decreased TNF-alpha secretion in ethanol treated cells. Further, lipid peroxidation, glutathione peroxidase and superoxide dismutase enzyme activities remained unaffected. Ethanol decreased glutathione content while, GSH/GSSG ratio was significantly higher compared to other groups showing cellular pro-oxidant and antioxidant balance remained

  20. Roles of the redox-active disulfide and histidine residues forming a catalytic dyad in reactions catalyzed by 2-ketopropyl coenzyme M oxidoreductase/carboxylase.

    Science.gov (United States)

    Kofoed, Melissa A; Wampler, David A; Pandey, Arti S; Peters, John W; Ensign, Scott A

    2011-09-01

    NADPH:2-ketopropyl-coenzyme M oxidoreductase/carboxylase (2-KPCC), an atypical member of the disulfide oxidoreductase (DSOR) family of enzymes, catalyzes the reductive cleavage and carboxylation of 2-ketopropyl-coenzyme M [2-(2-ketopropylthio)ethanesulfonate; 2-KPC] to form acetoacetate and coenzyme M (CoM) in the bacterial pathway of propylene metabolism. Structural studies of 2-KPCC from Xanthobacter autotrophicus strain Py2 have revealed a distinctive active-site architecture that includes a putative catalytic triad consisting of two histidine residues that are hydrogen bonded to an ordered water molecule proposed to stabilize enolacetone formed from dithiol-mediated 2-KPC thioether bond cleavage. Site-directed mutants of 2-KPCC were constructed to test the tenets of the mechanism proposed from studies of the native enzyme. Mutagenesis of the interchange thiol of 2-KPCC (C82A) abolished all redox-dependent reactions of 2-KPCC (2-KPC carboxylation or protonation). The air-oxidized C82A mutant, as well as wild-type 2-KPCC, exhibited the characteristic charge transfer absorbance seen in site-directed variants of other DSOR enzymes but with a pK(a) value for C87 (8.8) four units higher (i.e., four orders of magnitude less acidic) than that for the flavin thiol of canonical DSOR enzymes. The same higher pK(a) value was observed in native 2-KPCC when the interchange thiol was alkylated by the CoM analog 2-bromoethanesulfonate. Mutagenesis of the flavin thiol (C87A) also resulted in an inactive enzyme for steady-state redox-dependent reactions, but this variant catalyzed a single-turnover reaction producing a 0.8:1 ratio of product to enzyme. Mutagenesis of the histidine proximal to the ordered water (H137A) led to nearly complete loss of redox-dependent 2-KPCC reactions, while mutagenesis of the distal histidine (H84A) reduced these activities by 58 to 76%. A redox-independent reaction of 2-KPCC (acetoacetate decarboxylation) was not decreased for any of the

  1. Reduced Cardiovascular Mortality 10 Years after Supplementation with Selenium and Coenzyme Q10 for Four Years: Follow-Up Results of a Prospective Randomized Double-Blind Placebo-Controlled Trial in Elderly Citizens.

    Directory of Open Access Journals (Sweden)

    Urban Alehagen

    Full Text Available Selenium and coenzyme Q10 are important antioxidants in the body. As the intake of selenium is low in Europe, and the endogenous production of coenzyme Q10 decreases as age increases, an intervention trial using selenium and coenzyme Q10 for four years was performed. As previously reported, the intervention was accompanied by reduced cardiovascular mortality. The objective of the present study was to analyze cardiovascular mortality for up to 10 years after intervention, to evaluate if mortality differed in subgroups differentiated by gender, diabetes, ischemic heart disease (IHD, and functional class.Four-hundred forty-three healthy elderly individuals were included from a rural municipality in Sweden. All cardiovascular mortality was registered, and no participant was lost to the follow-up. Based on death certificates and autopsy results mortality was registered.Significantly reduced cardiovascular mortality could be seen in those on selenium and coenzyme Q10 intervention. A multivariate Cox regression analysis demonstrated a reduced cardiovascular mortality risk in the active treatment group (HR: 0.51; 95%CI 0.36-0.74; P = 0.0003. The reduced mortality could be seen to persist during the 10-year period. Subgroup analysis showed positive effects in both genders. An equally positive risk reduction could be seen in those with ischemic heart disease (HR: 0.51; 95%CI 0.27-0.97; P = 0.04, but also in the different functional classes.In a 10-year follow-up of a group of healthy elderly participants given four years of intervention with selenium and coenzyme Q10, significantly reduced cardiovascular mortality was observed. The protective action was not confined to the intervention period, but persisted during the follow-up period. The mechanism explaining the persistency remains to be elucidated. Since this was a small study, the observations should be regarded as hypothesis-generating.

  2. Synthesis of ethyl ( sup 14 CH sub 3 )methylmalonyl thioglycolate as a possible substrate analogue of ( sup 14 CH sub 3 )methylmalonyl coenzyme-A

    Energy Technology Data Exchange (ETDEWEB)

    Kovacs, I. (BIOGAL Pharmaceutical Works, Debrecen (Hungary)); Kovacs, Z. (Inst. of Nuclear Research, Debrecen (Hungary))

    1991-11-01

    Ethyl methylmalonyl thioglycolate is a potential substrate analogue of methylmalonyl-coenzyme-A (methylmalonyl-CoA) in the investigation of propionic acid metabolism. To prove this hypothesis, the tracer ethyl ({sup 14}CH{sub 3}) methylmalonyl thioglycolate was synthesized via methyl-Meldrum's acid to carry out the biochemical examinations. The method described can also be used to synthesize ({sup 14}CH{sub 3}) methylmalonyl-CoA by transesterification of active labelled methylmalonyl thiophenyl ester. This latter intermediate is chemically stable when stored at room temperature, and the unstable ({sup 14}CH{sub 3})methylmalonyl-CoA can be prepared in one step just preceeding the biochemical experiments. (author).

  3. Sterol-induced Dislocation of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase from Endoplasmic Reticulum Membranes into the Cytosol through a Subcellular Compartment Resembling Lipid Droplets*

    Science.gov (United States)

    Hartman, Isamu Z.; Liu, Pingsheng; Zehmer, John K.; Luby-Phelps, Katherine; Jo, Youngah; Anderson, Richard G. W.; DeBose-Boyd, Russell A.

    2010-01-01

    Sterol-induced binding to Insigs in the endoplasmic reticulum (ER) allows for ubiquitination of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in cholesterol synthesis. This ubiquitination marks reductase for recognition by the ATPase VCP/p97, which mediates extraction and delivery of reductase from ER membranes to cytosolic 26 S proteasomes for degradation. Here, we report that reductase becomes dislocated from ER membranes into the cytosol of sterol-treated cells. This dislocation exhibits an absolute requirement for the actions of Insigs and VCP/p97. Reductase also appears in a buoyant fraction of sterol-treated cells that co-purifies with lipid droplets, cytosolic organelles traditionally regarded as storage depots for neutral lipids such as triglycerides and cholesteryl esters. Genetic, biochemical, and localization studies suggest a model in which reductase is dislodged into the cytosol from an ER subdomain closely associated with lipid droplets. PMID:20406816

  4. Generation, genome edition and characterization of iPSC lines from a patient with coenzyme Q10 deficiency harboring a heterozygous mutation in COQ4 gene

    Directory of Open Access Journals (Sweden)

    Damià Romero-Moya

    2017-10-01

    Full Text Available We report the generation, CRISPR/Cas9-edition and characterization of induced pluripotent stem cell (iPSC lines from a patient with coenzyme Q10 deficiency harboring the heterozygous mutation c.483G > C in the COQ4 gene. iPSCs were generated using non-integrative Sendai Viruses containing the reprogramming factors OCT4, SOX2, KLF4 and C-MYC. The iPSC lines carried the c.483G > C COQ4 mutation, silenced the OKSM expression and were mycoplasma-free. They were bona fide pluripotent cells as characterized by morphology, immunophenotype/gene expression for pluripotent-associated markers/genes, NANOG and OCT4 promoter demethylation, karyotype and teratoma formation. The COQ4 mutation was CRISPR/Cas9 edited resulting in isogenic, diploid and off-target free COQ4-corrected iPSCs.

  5. A Direct Comparison of Anti-ulcer Effects of Coenzyme Q10 and Vitamin C on Indomethacin-induced Gastric Ulcer in Rat: A Controlled Experimental Study

    Directory of Open Access Journals (Sweden)

    2013-08-01

    Full Text Available Introduction: Indomethacin increases generation of mitochondrial reactive oxygen species (ROS which have a crucial role in the indomethacin-induced gastric ulcer. Coenzyme Q10 has an antioxidant activity on mitochondria and cell membranes and protects lipids from oxidation and is essential for stabilizing biological membranes. Superoxide dismutase (SOD acts as one of the defense mechanisms against free radicals. When the generation of ROS overwhelms, the antioxidant defense, lipid peroxiation of cell membrane occurs and cause cell damage. Materials and Methods: Male adult Wistar rats were divided into A and B groups. The rats in group A were then further divided into three subgroups of 6 animals each and received one of the following treatments: Animals in the first subgroup received saline. Animals in the second subgroup received saline and indomethacin. Animals in the third subgroup received vitamin C and indomethacin. The rats in group B were also further divided into 3 subgroups of 6 rats each and treated with one of the following treatments: Animals in first subgroup received 1% Tween 80 as vehicle. Animals In second subgroup received 1% Tween 80 and indomethacin. Animals in third subgroup received CoQ10 and indomethacin. Four hours after the last treatment, animals were killed and the stomachs removed were cut and gastric mucosal lesions were examined. Ulcer indexes were determined and SOD activity measured in plasma                                                             Results: Pretreatment with both vitamin C and coenzyme Q10 was associated with attenuation of ulcer index and increased SOD activity compared with animals treated with indomethacin alone (P

  6. Water-soluble Coenzyme Q10 formulation (Q-ter) promotes outer hair cell survival in a guinea pig model of noise induced hearing loss (NIHL).

    Science.gov (United States)

    Fetoni, Anna Rita; Piacentini, Roberto; Fiorita, Antonella; Paludetti, Gaetano; Troiani, Diana

    2009-02-27

    The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS) also in noise induced hearing loss (NIHL) and anti-oxidants and free-radicals scavengers have been shown to attenuate the damage. Coenzyme Q(10) (CoQ(10)) or ubiquinone has a bioenergetic role as a component of the mithocondrial respiratory chain, it inhibits mitochondrial lipid peroxidation, inducing ATP production and it is involved in ROS removal and prevention of oxidative stress-induced apoptosis. However the therapeutic application of CoQ(10) is limited by the lack of solubility and poor bio- availability, therefore it is a challenge to improve its water solubility in order to ameliorate the efficacy in tissues and fluids. This study was conducted in a model of acoustic trauma in the guinea pig where the effectiveness of CoQ(10) was compared with a soluble formulation of CoQ(10) (multicomposite CoQ(10) Terclatrate, Q-ter) given intraperitoneally 1 h before and once daily for 3 days after pure tone noise exposure (6 kHz for 1 h at 120 dB SPL). Functional and morphological studies were carried out by measuring auditory brainstem responses, scanning electron microscopy for hair cell loss count, active caspase 3 staining and terminal deoxynucleotidyl transferase-mediated dUTP labelling assay in order to identify initial signs of apoptosis. Treatments decreased active caspase 3 expression and the number of apoptotic cells, but animals injected with Q-ter showed a greater degree of activity in preventing apoptosis and thus in improving hearing. These data confirm that solubility of Coenzyme Q(10) improves the ability of CoQ(10) in preventing oxidative injuries that result from mitochondrial dysfunction.

  7. The effect of coenzyme Q10 included by γ-cyclodextrin on the growth of fission yeast studied by microscope Raman spectroscopy

    Science.gov (United States)

    Nishida, Tatsuro; Kaino, Tomohiro; Ikarashi, Ryo; Nakata, Daisuke; Terao, Keiji; Ando, Masahiro; Hamaguchi, Hiro-o.; Kawamukai, Makoto; Yamamoto, Tatsuyuki

    2013-09-01

    The inclusion complex of coenzyme Q10 (CoQ10) by γ-cyclodextrin (γ-CD), CoQ10-CD complex, was recently developed. The addition of the CoQ10-CD complex recovered the growth of a fission yeast mutant strain, Δdps1, which otherwise cannot grow well due to the lack of coenzyme Q producing ability. However, the oxygen consumption rate of this strain was not restored by the addition of the CoQ10-CD complex. The addition of two other anti-oxidative reagents, glutathione and ascorbic acid, also recovered the growth of the Δdps1 strain as well. These results indicated that the recovery of the growth of Δdps1 was brought about by the anti-oxidative property of CoQ10. The intensity of Raman spectra of Δdps1 at 1602 cm-1, which is prominently observed for the wild type of the fission yeast, was compared between before and after addition of the CoQ10-CD complex. The signal was very weakly observed for Δdps1 and did not increase in intensity by the addition of the CoQ10-CD complex. These results suggested the recovery of the growth of Δdps1 was brought about not by the restoration of respiration function of Δdps1 but by the anti-oxidative property of CoQ10 to result in the decrease in the oxidative stress.

  8. Tomo II

    OpenAIRE

    Llano Zapata, José Eusebio

    2015-01-01

    Memorias, histórico, físicas, crítico, apologéticas de la América Meridional con unas breves advertencias y noticias útiles, a los que de orden de Su Majestad hubiesen de viajar y describir aquellas vastas regiones. Reino Vegetal, Tomo II. Por un anónimo americano en Cádiz por los años de 1757. Muy Señor mío, juzgo que los 20 artículos del libro que remití a Vuestra Merced le habrán hecho formar el concepto que merece la fecundidad de aquellos países en las producciones minerales. Y siendo es...

  9. Cd(II), Cu(II)

    African Journals Online (AJOL)

    user

    Depending on the way goethite was pretreated with oxalic acid, affinity for Cd(II) varied ...... Effects and mechanisms of oxalate on Cd(II) adsorption on goethite at different ... precipitation, surfactant mediation, hydrothermal and micro-emulsion.

  10. Cu(II) AND Zn(II)

    African Journals Online (AJOL)

    Preferred Customer

    SYNTHESIS OF 2,2-DIMETHYL-4-PHENYL-[1,3]-DIOXOLANE USING ZEOLITE. ENCAPSULATED Co(II), Cu(II) AND Zn(II) COMPLEXES. B.P. Nethravathi1, K. Rama Krishna Reddy2 and K.N. Mahendra1*. 1Department of Chemistry, Bangalore University, Bangalore-560001, India. 2Department of Chemistry, Government ...

  11. Elizabeth II uus kunstigalerii

    Index Scriptorium Estoniae

    1999-01-01

    Tähistamaks oma troonile asumise 50. aastapäeva, avab Elizabeth II 6. II 2002 Buckinghami palees uue kunstigalerii, mis ehitatakse palee tiibhoonena. Arhitekt John Simpson. Elizabeth II kunstikogust

  12. Fermentation of mixed glucose-xylose substrates by engineered strains of Saccharomyces cerevisiae: role of the coenzyme specificity of xylose reductase, and effect of glucose on xylose utilization

    Directory of Open Access Journals (Sweden)

    Klimacek Mario

    2010-03-01

    Full Text Available Abstract Background In spite of the substantial metabolic engineering effort previously devoted to the development of Saccharomyces cerevisiae strains capable of fermenting both the hexose and pentose sugars present in lignocellulose hydrolysates, the productivity of reported strains for conversion of the naturally most abundant pentose, xylose, is still a major issue of process efficiency. Protein engineering for targeted alteration of the nicotinamide cofactor specificity of enzymes catalyzing the first steps in the metabolic pathway for xylose was a successful approach of reducing xylitol by-product formation and improving ethanol yield from xylose. The previously reported yeast strain BP10001, which expresses heterologous xylose reductase from Candida tenuis in mutated (NADH-preferring form, stands for a series of other yeast strains designed with similar rational. Using 20 g/L xylose as sole source of carbon, BP10001 displayed a low specific uptake rate qxylose (g xylose/g dry cell weight/h of 0.08. The study presented herein was performed with the aim of analysing (external factors that limit qxylose of BP10001 under xylose-only and mixed glucose-xylose substrate conditions. We also carried out a comprehensive investigation on the currently unclear role of coenzyme utilization, NADPH compared to NADH, for xylose reduction during co-fermentation of glucose and xylose. Results BP10001 and BP000, expressing C. tenuis xylose reductase in NADPH-preferring wild-type form, were used. Glucose and xylose (each at 10 g/L were converted sequentially, the corresponding qsubstrate values being similar for each strain (glucose: 3.0; xylose: 0.05. The distribution of fermentation products from glucose was identical for both strains whereas when using xylose, BP10001 showed enhanced ethanol yield (BP10001 0.30 g/g; BP000 0.23 g/g and decreased yields of xylitol (BP10001 0.26 g/g; BP000 0.36 g/g and glycerol (BP10001 0.023 g/g; BP000 0.072 g/g as compared

  13. Gene structure and mutations of glutaryl-coenzyme A dehydrogenase: impaired association of enzyme subunits that is due to an A421V substitution causes glutaric acidemia type I in the Amish.

    OpenAIRE

    Biery, B. J.; Stein, D. E.; Morton, D. H.; Goodman, S. I.

    1996-01-01

    The structure of the human glutaryl coenzyme A dehydrogenase (GCD) gene was determined to contain 11 exons and to span approximately 7 kb. Fibroblast DNA from 64 unrelated glutaric acidemia type I (GA1) patients was screened for mutations by PCR amplification and analysis of SSCP. Fragments with altered electrophoretic mobility were subcloned and sequenced to detect mutations that caused GA1. This report describes the structure of the GCD gene, as well as point mutations and polymorphisms fou...

  14. Specific DNA Binding of a Potential Transcriptional Regulator, Inosine 5′-Monophosphate Dehydrogenase-Related Protein VII, to the Promoter Region of a Methyl Coenzyme M Reductase I-Encoding Operon Retrieved from Methanothermobacter thermautotrophicus Strain ΔH▿

    OpenAIRE

    Shinzato, Naoya; Enoki, Miho; Sato, Hiroaki; Nakamura, Kohei; Matsui, Toru; Kamagata, Yoichi

    2008-01-01

    Two methyl coenzyme M reductases (MCRs) encoded by the mcr and mrt operons of the hydrogenotrophic methanogen Methanothermobacter thermautotrophicus ΔH are expressed in response to H2 availability. In the present study, cis elements and trans-acting factors responsible for the gene expression of MCRs were investigated by using electrophoretic mobility shift assay (EMSA) and affinity particle purification. A survey of their operator regions by EMSA with protein extracts from mrt-expressing cul...

  15. Three endoplasmic reticulum-associated fatty acyl-coenzyme a reductases were involved in the production of primary alcohols in hexaploid wheat (Triticum aestivum L.).

    Science.gov (United States)

    Chai, Guaiqiang; Li, Chunlian; Xu, Feng; Li, Yang; Shi, Xue; Wang, Yong; Wang, Zhonghua

    2018-03-05

    The cuticle covers the surface of the polysaccharide cell wall of leaf epidermal cells and forms an essential diffusion barrier between the plant and the environment. The cuticle is composed of cutin and wax. Cuticular wax plays an important role in the survival of plants by serving as the interface between plants and their biotic and abiotic environments, especially restricting nonstomatal water loss. Leaf cuticular waxes of hexaploid wheat at the seedling stage mainly consist of primary alcohols, aldehydes, fatty acids, alkane and esters. Primary alcohols account for more than 80% of the total wax load. Therefore, we cloned several genes encoding fatty acyl-coenzyme A reductases from wheat and analyzed their function in yeast and plants. We propose the potential use of these genes in wheat genetic breeding. We reported the cloning and characterization of three TaFARs, namely TaFAR6, TaFAR7 and TaFAR8, encoding fatty acyl-coenzyme A reductases (FAR) in wheat leaf cuticle. Expression analysis revealed that TaFAR6, TaFAR7 and TaFAR8 were expressed at the higher levels in the seedling leaf blades, and were expressed moderately or weakly in stamen, glumes, peduncle, flag leaf blade, sheath, spike, and pistil. The heterologous expression of three TaFARs in yeast (Saccharomyces cerevisiae) led to the production of C24:0 and C26:0 primary alcohols. Transgenic expression of the three TaFARs in tomato (Solanum lycopersicum) and rice (Oryza sativa) led to increased accumulation of C24:0-C30:0 primary alcohols. Transient expression of GFP protein-tagged TaFARs revealed that the three TaFAR proteins were localized to the endoplasmic reticulum (ER), the site of wax biosynthesis. The three TaFAR genes were transcriptionally induced by drought, cold, heat, powdery mildew (Blumeria graminis) infection, abscisic acid (ABA) and methyl jasmonate (MeJa) treatments. These results indicated that wheat TaFAR6, TaFAR7 and TaFAR8 are involved in biosynthesis of very-long-chain primary

  16. Paraquat induces oxidative stress, neuronal loss in substantia nigra region and Parkinsonism in adult rats: Neuroprotection and amelioration of symptoms by water-soluble formulation of Coenzyme Q10

    Directory of Open Access Journals (Sweden)

    Sridhar TS

    2009-07-01

    Full Text Available Abstract Background Parkinson's disease, for which currently there is no cure, develops as a result of progressive loss of dopamine neurons in the brain; thus, identification of any potential therapeutic intervention for disease management is of a great importance. Results Here we report that prophylactic application of water-soluble formulation of coenzyme Q10 could effectively offset the effects of environmental neurotoxin paraquat, believed to be a contributing factor in the development of familial PD. In this study we utilized a model of paraquat-induced dopaminergic neurodegeneration in adult rats that received three weekly intra-peritoneal injections of the herbicide paraquat. Histological and biochemical analyses of rat brains revealed increased levels of oxidative stress markers and a loss of approximately 65% of dopamine neurons in the substantia nigra region. The paraquat-exposed rats also displayed impaired balancing skills on a slowly rotating drum (rotorod evidenced by their reduced spontaneity in gait performance. In contrast, paraquat exposed rats receiving a water-soluble formulation of coenzyme Q10 in their drinking water prior to and during the paraquat treatment neither developed neurodegeneration nor reduced rotorod performance and were indistinguishable from the control paraquat-untreated rats. Conclusion Our data confirmed that paraquat-induced neurotoxicity represents a convenient rat model of Parkinsonian neurodegeneration suitable for mechanistic and neuroprotective studies. This is the first preclinical evaluation of a water-soluble coenzyme Q10 formulation showing the evidence of prophylactic neuroprotection at clinically relevant doses.

  17. Synthesis and characterisation of Cu(II), Ni(II), Mn(II), Zn(II) and VO(II ...

    Indian Academy of Sciences (India)

    Unknown

    Synthesis and characterisation of Cu(II), Ni(II), Mn(II), Zn(II) and VO(II) Schiff base complexes derived from o-phenylenediamine and acetoacetanilide. N RAMAN*, Y PITCHAIKANI RAJA and A KULANDAISAMY. Department of Chemistry, VHNSN College, Virudhunagar 626 001, India e-mail: ra_man@123india.com.

  18. Coupled Ferredoxin and Crotonyl Coenzyme A (CoA) Reduction with NADH Catalyzed by the Butyryl-CoA Dehydrogenase/Etf Complex from Clostridium kluyveri▿ †

    Science.gov (United States)

    Li, Fuli; Hinderberger, Julia; Seedorf, Henning; Zhang, Jin; Buckel, Wolfgang; Thauer, Rudolf K.

    2008-01-01

    Cell extracts of butyrate-forming clostridia have been shown to catalyze acetyl-coenzyme A (acetyl-CoA)- and ferredoxin-dependent formation of H2 from NADH. It has been proposed that these bacteria contain an NADH:ferredoxin oxidoreductase which is allosterically regulated by acetyl-CoA. We report here that ferredoxin reduction with NADH in cell extracts from Clostridium kluyveri is catalyzed by the butyryl-CoA dehydrogenase/Etf complex and that the acetyl-CoA dependence previously observed is due to the fact that the cell extracts catalyze the reduction of acetyl-CoA with NADH via crotonyl-CoA to butyryl-CoA. The cytoplasmic butyryl-CoA dehydrogenase complex was purified and is shown to couple the endergonic reduction of ferredoxin (E0′ = −410 mV) with NADH (E0′ = −320 mV) to the exergonic reduction of crotonyl-CoA to butyryl-CoA (E0′ = −10 mV) with NADH. The stoichiometry of the fully coupled reaction is extrapolated to be as follows: 2 NADH + 1 oxidized ferredoxin + 1 crotonyl-CoA = 2 NAD+ + 1 ferredoxin reduced by two electrons + 1 butyryl-CoA. The implications of this finding for the energy metabolism of butyrate-forming anaerobes are discussed in the accompanying paper. PMID:17993531

  19. Coupled ferredoxin and crotonyl coenzyme A (CoA) reduction with NADH catalyzed by the butyryl-CoA dehydrogenase/Etf complex from Clostridium kluyveri.

    Science.gov (United States)

    Li, Fuli; Hinderberger, Julia; Seedorf, Henning; Zhang, Jin; Buckel, Wolfgang; Thauer, Rudolf K

    2008-02-01

    Cell extracts of butyrate-forming clostridia have been shown to catalyze acetyl-coenzyme A (acetyl-CoA)- and ferredoxin-dependent formation of H2 from NADH. It has been proposed that these bacteria contain an NADH:ferredoxin oxidoreductase which is allosterically regulated by acetyl-CoA. We report here that ferredoxin reduction with NADH in cell extracts from Clostridium kluyveri is catalyzed by the butyryl-CoA dehydrogenase/Etf complex and that the acetyl-CoA dependence previously observed is due to the fact that the cell extracts catalyze the reduction of acetyl-CoA with NADH via crotonyl-CoA to butyryl-CoA. The cytoplasmic butyryl-CoA dehydrogenase complex was purified and is shown to couple the endergonic reduction of ferredoxin (E0' = -410 mV) with NADH (E0' = -320 mV) to the exergonic reduction of crotonyl-CoA to butyryl-CoA (E0' = -10 mV) with NADH. The stoichiometry of the fully coupled reaction is extrapolated to be as follows: 2 NADH + 1 oxidized ferredoxin + 1 crotonyl-CoA = 2 NAD+ + 1 ferredoxin reduced by two electrons + 1 butyryl-CoA. The implications of this finding for the energy metabolism of butyrate-forming anaerobes are discussed in the accompanying paper.

  20. Pharmacological Chaperones and Coenzyme Q10 Treatment Improves Mutant β-Glucocerebrosidase Activity and Mitochondrial Function in Neuronopathic Forms of Gaucher Disease

    Science.gov (United States)

    de la Mata, Mario; Cotán, David; Oropesa-Ávila, Manuel; Garrido-Maraver, Juan; Cordero, Mario D.; Villanueva Paz, Marina; Delgado Pavón, Ana; Alcocer-Gómez, Elizabet; de Lavera, Isabel; Ybot-González, Patricia; Paula Zaderenko, Ana; Ortiz Mellet, Carmen; Fernández, José M. García; Sánchez-Alcázar, José A.

    2015-01-01

    Gaucher disease (GD) is caused by mutations in the GBA1 gene, which encodes lysosomal β-glucocerebrosidase. Homozygosity for the L444P mutation in GBA1 is associated with high risk of neurological manifestations which are not improved by enzyme replacement therapy. Alternatively, pharmacological chaperones (PCs) capable of restoring the correct folding and trafficking of the mutant enzyme represent promising alternative therapies.Here, we report on how the L444P mutation affects mitochondrial function in primary fibroblast derived from GD patients. Mitochondrial dysfunction was associated with reduced mitochondrial membrane potential, increased reactive oxygen species (ROS), mitophagy activation and impaired autophagic flux.Both abnormalities, mitochondrial dysfunction and deficient β-glucocerebrosidase activity, were partially restored by supplementation with coenzyme Q10 (CoQ) or a L-idonojirimycin derivative, N-[N’-(4-adamantan-1-ylcarboxamidobutyl)thiocarbamoyl]-1,6-anhydro-L-idonojirimycin (NAdBT-AIJ), and more markedly by the combination of both treatments. These data suggest that targeting both mitochondria function by CoQ and protein misfolding by PCs can be promising therapies in neurological forms of GD. PMID:26045184

  1. Three-dimensional structure of phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis in the apo form and in complexes with coenzyme A and dephosphocoenzyme A

    International Nuclear Information System (INIS)

    Timofeev, V. I.; Smirnova, E. A.; Chupova, L. A.; Esipov, R. S.; Kuranova, I. P.

    2012-01-01

    Crystals of phosphopantetheine adenylyltransferase (PPAT) from Mycobacterium tuberculosis in the apo form and in complexes with coenzyme A (PPAT/CoA) and dephosphocoenzyme A (PPAT/dPCoA) were grown in microgravity by the capillary counter-diffusion method. The structures of PPAT Mt in the apo form and in complexes with ligands were solved based on the X-ray diffraction data collected from the grown crystals. The crystal structures were refined at 1.76, 1.59, and 1.59 Å resolution to Rf factors of 0.175, 0.159, and 0.157 and Rfree of 0.224, 0.208, and 0.206 for PPAT, PPAT/CoA, and PPAT/dPCoA, respectively. The atomic coordinates of the structures were deposited in the Protein Data Bank (PDB ID: 3RFF, 3RHS, and 3RBA). In these structures, the ligand-binding sites were determined, the environment of these sites was characterized, and the conformational changes accompanying the ligand binding were analyzed.

  2. Analysis of five rice 4-coumarate:coenzyme A ligase enzyme activity and stress response for potential roles in lignin and flavonoid biosynthesis in rice

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Haiyan [National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070 (China); Biomass and Bioenergy Research Centre, Huazhong Agricultural University, Wuhan 430070 (China); College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); School of Biology and Food Engineering, Changshu Institute of Technology, Changshu 215500 (China); Li, Ying; Feng, Shengqiu; Zou, Weihua [National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070 (China); Biomass and Bioenergy Research Centre, Huazhong Agricultural University, Wuhan 430070 (China); College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Guo, Kai [National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070 (China); Biomass and Bioenergy Research Centre, Huazhong Agricultural University, Wuhan 430070 (China); College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Fan, Chunfen [National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070 (China); Biomass and Bioenergy Research Centre, Huazhong Agricultural University, Wuhan 430070 (China); College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Si, Shengli [National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070 (China); Biomass and Bioenergy Research Centre, Huazhong Agricultural University, Wuhan 430070 (China); College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); and others

    2013-01-18

    Highlights: ► 4CLs play important roles in both lignin and flavonoids biosynthesis. ► PA and FA are the two main substrates of 4CL (Os4CL1/3/4/5) for lignin biosynthesis. ► Os4CL2 is suggested for flavonoid formation in defense against UV radiation. -- Abstract: 4-Coumarate:coenzyme A ligase (4CL) catalyzes the conversion of hydroxycinnamates into corresponding CoA esters for biosynthesis of flavonoids and lignin. In this study, five members of the 4CL gene family from rice were cloned and analyzed. Recombinant 4CL data revealed that 4-coumaric acid and ferulic acid were the two main substrates of 4CL (Os4CL1/3/4/5) for monolignol biosynthesis in rice. Os4CL2 was specifically expressed in the anther and was strongly activated by UV irradiation, suggesting its potential involvement in flavonoid formation. Moreover, bioinformatics analysis showed that the existence of valine residue at the substrate-binding pocket may mainly affect rice 4CL activities toward sinapic acid.

  3. Characterization of oat beta-glucan and coenzyme Q10-loaded beta-glucan powders generated by the pressurized gas-expanded liquid (PGX) technology.

    Science.gov (United States)

    Liu, Nian; Couto, Ricardo; Seifried, Bernhard; Moquin, Paul; Delgado, Luis; Temelli, Feral

    2018-04-01

    The physicochemical properties of the oat beta-glucan powder (BG) and coenzyme Q10 (CoQ10)-loaded BG powder (L-BG) produced by the pressurized gas-expanded liquid (PGX) technology were studied. Helium ion microscope, differential scanning calorimeter, X-ray diffractometer, AutoSorb iQ and rheometer were used to determine the particle morphology, thermal properties, crystallinity, surface area and viscosity, respectively. Both BG (7.7μm) and L-BG (6.1μm) were produced as micrometer-scale particles, while CoQ10 nanoparticles (92nm) were adsorbed on the porous structure of L-BG. CoQ10 was successfully loaded onto BG using the PGX process via adsorptive precipitation mainly in its amorphous form. Viscosity of BG and L-BG solutions (0.15%, 0.2%, 0.3% w/v) displayed Newtonian behavior with increasing shear rate but decreased with temperature. Detailed characterization of the physicochemical properties of combination ingredients like L-BG will lead to the development of novel functional food and natural health product applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Effects of coenzyme Q10 supplementation on the anthropometric variables, lipid profiles and liver enzymes in patients with non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Elnaz Jafarvand

    2016-03-01

    Full Text Available This randomized double-blind placebo-controlled trial was conducted on 41 patients with non-alcoholic fatty liver disease. Patients in intervention group received 100 mg/day coenzyme Q10 (CoQ10 for four weeks. There was a significant reduction in waist circumference and aspartate aminotransferase concentrations after CoQ10 supplementation (p<0.05. Dietary fiber was in negative correlation with change in serum alanine aminotransferase (ALT concentrations (r = -410, p = 0.04, and dietary fat intake was in positive relation with serum triglyceride (r = 463, p = 0.04 and in negative relation with serum high-density lipoprotein cholesterol (HDL-C (r = -533, p = 0.02 in CoQ10-treated group. CoQ10 supplement is able to reduce central obesity and improve liver function in non-alcoholic fatty liver disease. Dietary factors were also significant determinants of change in liver-specific enzyme ALT and lipid profile in these patients. Further trials with higher dose of CoQ10 and longer treatment periods are warranted to better clarify these findings.

  5. Methamphetamine-induced neuronal protein NAT8L is the NAA biosynthetic enzyme: implications for specialized acetyl coenzyme A metabolism in the CNS.

    Science.gov (United States)

    Ariyannur, Prasanth S; Moffett, John R; Manickam, Pachiappan; Pattabiraman, Nagarajan; Arun, Peethambaran; Nitta, Atsumi; Nabeshima, Toshitaka; Madhavarao, Chikkathur N; Namboodiri, Aryan M A

    2010-06-04

    N-acetylaspartate (NAA) is a concentrated, neuron-specific brain metabolite routinely used as a magnetic resonance spectroscopy marker for brain injury and disease. Despite decades of research, the functional roles of NAA remain unclear. Biochemical investigations over several decades have associated NAA with myelin lipid synthesis and energy metabolism. However, studies have been hampered by an inability to identify the gene for the NAA biosynthetic enzyme aspartate N-acetyltransferase (Asp-NAT). A very recent report has identified Nat8l as the gene encoding Asp-NAT and confirmed that the only child diagnosed with a lack of NAA on brain magnetic resonance spectrograms has a 19-bp deletion in this gene. Based on in vitro Nat8l expression studies the researchers concluded that many previous biochemical investigations have been technically flawed and that NAA may not be associated with brain energy or lipid metabolism. In studies done concurrently in our laboratory we have demonstrated via cloning, expression, specificity for acetylation of aspartate, responsiveness to methamphetamine treatment, molecular modeling and comparative immunolocalization that NAT8L is the NAA biosynthetic enzyme Asp-NAT. We conclude that NAA is a major storage and transport form of acetyl coenzyme A specific to the nervous system, thus linking it to both lipid synthesis and energy metabolism. Published by Elsevier B.V.

  6. Analysis of five rice 4-coumarate:coenzyme A ligase enzyme activity and stress response for potential roles in lignin and flavonoid biosynthesis in rice

    International Nuclear Information System (INIS)

    Sun, Haiyan; Li, Ying; Feng, Shengqiu; Zou, Weihua; Guo, Kai; Fan, Chunfen; Si, Shengli

    2013-01-01

    Highlights: ► 4CLs play important roles in both lignin and flavonoids biosynthesis. ► PA and FA are the two main substrates of 4CL (Os4CL1/3/4/5) for lignin biosynthesis. ► Os4CL2 is suggested for flavonoid formation in defense against UV radiation. -- Abstract: 4-Coumarate:coenzyme A ligase (4CL) catalyzes the conversion of hydroxycinnamates into corresponding CoA esters for biosynthesis of flavonoids and lignin. In this study, five members of the 4CL gene family from rice were cloned and analyzed. Recombinant 4CL data revealed that 4-coumaric acid and ferulic acid were the two main substrates of 4CL (Os4CL1/3/4/5) for monolignol biosynthesis in rice. Os4CL2 was specifically expressed in the anther and was strongly activated by UV irradiation, suggesting its potential involvement in flavonoid formation. Moreover, bioinformatics analysis showed that the existence of valine residue at the substrate-binding pocket may mainly affect rice 4CL activities toward sinapic acid

  7. Development of a photoelectrochemical lactic dehydrogenase biosensor using multi-wall carbon nanotube-TiO2 nanoparticle composite as coenzyme regeneration tool

    International Nuclear Information System (INIS)

    Liu, Xiaoqiang; Yan, Rui; Zhu, Jie; Huo, Xiaohe; Wang, Xinhai

    2015-01-01

    Highlights: •Multi-wall Carbon Nanotube-TiO 2 nanoparticle composite was synthesized by hydrothermal method •The composite was characterized by TEM, XRD, FT-IR •A photoelectrochemical (PEC) lactic dehydrogenase (LDH) biosensor was developed based on the composite •The composite acts as both coenzyme regeneration tool and immobilization material •The PEC biosensor shows superiority over the electrochemical LDH biosensors in analytical performance -- Abstract: A novel photoelectrochemical (PEC) lactic dehydrogenase (LDH) biosensor was developed based on a multi-wall carbon nanotube (MWCNT)-TiO 2 nanoparticle (TNP) composite platform. This composite platform can not only aid in regeneration of nicotinamide adenine dinucleotide (NAD + ) in the enzymatic cycle, but also immobilize enzymes on electrode surface. TNPs were grown on MWCNT surface through a hydrothermal method and the composite was characterized by various spectroscopic techniques. The electrochemical performance of the LDH biosensors has demonstrated that the composite is a feasible immobilization matrix for LDH. The PEC experiments have confirmed that NAD + can be regenerated by the holes produced by irradiating MWCNT-TNP composite to fulfill the enzyme catalytic cycle. The analytical performance of the PEC LDH biosensor was studied by measuring its photocurrents. The dynamic range, sensitivity and limit of detection of the biosensor were estimated to be 0.5 to 120 μM, 0.0242 μA μM −1 and 0.1 μM respectively, which are superior to those of electrochemical LDH biosensors

  8. Cloning, Expression Profiling and Functional Analysis of CnHMGS, a Gene Encoding 3-hydroxy-3-Methylglutaryl Coenzyme A Synthase from Chamaemelum nobile.

    Science.gov (United States)

    Cheng, Shuiyuan; Wang, Xiaohui; Xu, Feng; Chen, Qiangwen; Tao, Tingting; Lei, Jing; Zhang, Weiwei; Liao, Yongling; Chang, Jie; Li, Xingxiang

    2016-03-08

    Roman chamomile (Chamaemelum nobile L.) is renowned for its production of essential oils, which major components are sesquiterpenoids. As the important enzyme in the sesquiterpenoid biosynthesis pathway, 3-hydroxy-3-methylglutaryl coenzyme A synthase (HMGS) catalyze the crucial step in the mevalonate pathway in plants. To isolate and identify the functional genes involved in the sesquiterpene biosynthesis of C. nobile L., a HMGS gene designated as CnHMGS (GenBank Accession No. KU529969) was cloned from C. nobile. The cDNA sequence of CnHMGS contained a 1377 bp open reading frame encoding a 458-amino-acid protein. The sequence of the CnHMGS protein was highly homologous to those of HMGS proteins from other plant species. Phylogenetic tree analysis revealed that CnHMGS clustered with the HMGS of Asteraceae in the dicotyledon clade. Further functional complementation of CnHMGS in the mutant yeast strain YSC6274 lacking HMGS activity demonstrated that the cloned CnHMGS cDNA encodes a functional HMGS. Transcript profile analysis indicated that CnHMGS was preferentially expressed in flowers and roots of C. nobile. The expression of CnHMGS could be upregulated by exogenous elicitors, including methyl jasmonate and salicylic acid, suggesting that CnHMGS was elicitor-responsive. The characterization and expression analysis of CnHMGS is helpful to understand the biosynthesis of sesquiterpenoid in C. nobile at the molecular level and also provides molecular wealth for the biotechnological improvement of this important medicinal plant.

  9. Age-Related Loss in Bone Mineral Density of Rats Fed Lifelong on a Fish Oil-Based Diet Is Avoided by Coenzyme Q10 Addition

    Directory of Open Access Journals (Sweden)

    Alfonso Varela-López

    2017-02-01

    Full Text Available During aging, bone mass declines increasing osteoporosis and fracture risks. Oxidative stress has been related to this bone loss, making dietary compounds with antioxidant properties a promising weapon. Male Wistar rats were maintained for 6 or 24 months on diets with fish oil as unique fat source, supplemented or not with coenzyme Q10 (CoQ10, to evaluate the potential of adding this molecule to the n-3 polyunsaturated fatty acid (n-3 PUFA-based diet for bone mineral density (BMD preservation. BMD was evaluated in the femur. Serum osteocalcin, osteopontin, receptor activator of nuclear factor-κB ligand, ostroprotegerin, parathyroid hormone, urinary F2-isoprostanes, and lymphocytes DNA strand breaks were also measured. BMD was lower in aged rats fed a diet without CoQ10 respect than their younger counterparts, whereas older animals receiving CoQ10 showed the highest BMD. F2-isoprostanes and DNA strand breaks showed that oxidative stress was higher during aging. Supplementation with CoQ10 prevented oxidative damage to lipid and DNA, in young and old animals, respectively. Reduced oxidative stress associated to CoQ10 supplementation of this n-3 PUFA-rich diet might explain the higher BMD found in aged rats in this group of animals.

  10. Water-Soluble Coenzyme Q10 Inhibits Nuclear Translocation of Apoptosis Inducing Factor and Cell Death Caused by Mitochondrial Complex I Inhibition

    Directory of Open Access Journals (Sweden)

    Haining Li

    2014-07-01

    Full Text Available The objectives of the study were to explore the mechanism of rotenone-induced cell damage and to examine the protective effects of water-soluble Coenzyme Q10 (CoQ10 on the toxic effects of rotenone. Murine hippocampal HT22 cells were cultured with mitochondrial complex I inhibitor rotenone. Water-soluble CoQ10 was added to the culture media 3 h prior to the rotenone incubation. Cell viability was determined by alamar blue, reactive oxygen species (ROS production by dihydroethidine (DHE and mitochondrial membrane potential by tetramethyl rhodamine methyl ester (TMRM. Cytochrome c, caspase-9 and apoptosis-inducing factor (AIF were measured using Western blotting after 24 h rotenone incubation. Rotenone caused more than 50% of cell death, increased ROS production, AIF nuclear translocation and reduction in mitochondrial membrane potential, but failed to cause mitochondrial cytochrome c release and caspase-9 activation. Pretreatment with water-soluble CoQ10 enhanced cell viability, decreased ROS production, maintained mitochondrial membrane potential and prevented AIF nuclear translocation. The results suggest that rotenone activates a mitochondria-initiated, caspase-independent cell death pathway. Water-soluble CoQ10 reduces ROS accumulation, prevents the fall of mitochondrial membrane potential, and inhibits AIF translocation and subsequent cell death.

  11. Coenzyme Q10 Inhibits the Aging of Mesenchymal Stem Cells Induced by D-Galactose through Akt/mTOR Signaling

    Directory of Open Access Journals (Sweden)

    Dayong Zhang

    2015-01-01

    Full Text Available Increasing evidences indicate that reactive oxygen species are the main factor promoting stem cell aging. Recent studies have demonstrated that coenzyme Q10 (CoQ10 plays a positive role in organ and cellular aging. However, the potential for CoQ10 to protect stem cell aging has not been fully evaluated, and the mechanisms of cell senescence inhibited by CoQ10 are still poorly understood. Our previous study had indicated that D-galactose (D-gal can remarkably induce mesenchymal stem cell (MSC aging through promoting intracellular ROS generation. In this study, we showed that CoQ10 could significantly inhibit MSC aging induced by D-gal. Moreover, in the CoQ10 group, the expression of p-Akt and p-mTOR was clearly reduced compared with that in the D-gal group. However, after Akt activating by CA-Akt plasmid, the senescence-cell number in the CoQ10 group was significantly higher than that in the control group. These results indicated that CoQ10 could inhibit D-gal-induced MSC aging through the Akt/mTOR signaling.

  12. From nicotinate-containing layered double hydroxides (LDHs) to NAD coenzyme-LDH nanocomposites - Syntheses and structural characterization by various spectroscopic methods

    Science.gov (United States)

    Muráth, Szabolcs; Dudás, Csilla; Kukovecz, Ákos; Kónya, Zoltán; Sipos, Pál; Pálinkó, István

    2017-07-01

    The syntheses of nicotinate anion- and NAD coenzyme-layered double hydroxide (LDH) composites were performed with the aim of having the organic component among the layers. In-house prepared CaAl-LDHs were the host materials. Intercalation was attempted by direct ion exchange or by the dehydration-rehydration method applying aqueous solvent mixtures (containing ethanol, propanol, acetone, N,N-dimethylformamide). For structural characterization, beside X-ray diffractometry, X-ray photoelectron and IR spectroscopies, transmission and scanning electron microscopies as well as energy-dispersive X-ray analysis were used. Molecular modelling served for the visualization of the arrangements of the intercalated ions among the layers of the LDH samples. Although not all the intercalation methods and solvent mixtures led to intercalated composite materials, successful ones could be identified. The combination of spectroscopic methods helped in proposing sensible spatial arrangements for the intercalated anions. The NAD-CaAl-LDH composite proved to be an active catalyst in the oxidation of hydroquinone to 1,4-bezoquinoe in the presence of H2O2.

  13. Preparation and in vitro-in vivo evaluation of Witepsol H35 based self-nanoemulsifying drug delivery systems (SNEDDS) of coenzyme Q(10).

    Science.gov (United States)

    Nepal, Pushp R; Han, Hyo-Kyung; Choi, Hoo-Kyun

    2010-02-19

    Coenzyme Q(10) (CoQ(10)) was formulated into self-nanoemulsifying drug delivery systems (SNEDDS) to overcome low bioavailability attributed to hydrophobic nature of the drug. Screening of oil phase, surfactants and co-surfactants were performed to select Witepsol H35, Solutol HS15 and Lauroglycol FCC, respectively. Ternary phase diagrams were drawn to identify nanoemulsifying region followed by optimization of SNEDDS formulation. The optimized formulation, CoQ(10), Witepsol H35, Solutol HS15 and Lauroglycol FCC in the weight ratio of 1:0.7:4:2, respectively, emulsified readily at 37 degrees C with mean emulsion droplet size of 32.4 nm. The stability test of the optimized formulation in pH 1.2 and 6.8 buffers confirmed no pH effect on emulsion droplet size. In vitro dissolution (emulsification) test and in vivo animal study of the formulation elucidated the complete emulsification of drug and improved oral bioavailability of poorly soluble CoQ(10). 2009 Elsevier B.V. All rights reserved.

  14. Arachidonic acid alters tomato HMG expression and fruit growth and induces 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent lycopene accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Concepcion, M.; Gruissem, W. [Univ. of California, Berkeley, CA (United States). Dept. of Plant and Microbial Biology

    1999-01-01

    Regulation of isoprenoid end-product synthesis required for normal growth and development in plants is not well understood. To investigate the extent to which specific genes for the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) are involved in end-product regulation, the authors manipulated expression of the HMG1 and HMG2 genes in tomato (Lycopersicon esculentum) fruit using arachidonic acid (AA). In developing young fruit AA blocked fruit growth, inhibited HMG1, and activated HMG2 expression. These results are consistent with other reports indicating that HMG1 expression is closely correlated with growth processes requiring phytosterol production. In mature-green fruit AA strongly induced the expression of HMG2, PSY1 (the gene for phytoene synthase), and lycopene accumulation before the normal onset of carotenoid synthesis and ripening. The induction of lycopene synthesis was not blocked by inhibition of HMGR activity using mevinolin, suggesting that cytoplasmic HMGR is not required for carotenoid synthesis. Their results are consistent with the function of an alternative plastid isoprenoid pathway (the Rohmer pathway) that appears to direct the production of carotenoids during tomato fruit ripening.

  15. The Combination of Physical Exercise with Muscle-Directed Antioxidants to Counteract Sarcopenia: A Biomedical Rationale for Pleiotropic Treatment with Creatine and Coenzyme Q10

    Directory of Open Access Journals (Sweden)

    Michele Guescini

    2017-01-01

    Full Text Available Sarcopenia represents an increasing public health risk due to the rapid aging of the world’s population. It is characterized by both low muscle mass and function and is associated with mobility disorders, increased risk of falls and fractures, loss of independence, disabilities, and increased risk of death. Despite the urgency of the problem, the development of treatments for sarcopenia has lagged. Increased reactive oxygen species (ROS production and decreased antioxidant (AO defences seem to be important factors contributing to muscle impairment. Studies have been conducted to verify whether physical exercise and/or AOs could prevent and/or delay sarcopenia through a normalization of the etiologically relevant ROS imbalance. Despite the strong rationale, the results obtained were contradictory, particularly with regard to the effects of the tested AOs. A possible explanation might be that not all the agents included in the general heading of “AOs” could fulfill the requisites to counteract the complex series of events causing/accelerating sarcopenia: the combination of the muscle-directed antioxidants creatine and coenzyme Q10 with physical exercise as a biomedical rationale for pleiotropic prevention and/or treatment of sarcopenia is discussed.

  16. Overexpression of the Squalene Epoxidase Gene Alone and in Combination with the 3-Hydroxy-3-methylglutaryl Coenzyme A Gene Increases Ganoderic Acid Production in Ganoderma lingzhi.

    Science.gov (United States)

    Zhang, De-Huai; Jiang, Lu-Xi; Li, Na; Yu, Xuya; Zhao, Peng; Li, Tao; Xu, Jun-Wei

    2017-06-14

    The squalene epoxidase (SE) gene from the biosynthetic pathway of ganoderic acid (GA) was cloned and overexpressed in Ganoderma lingzhi. The strain that overexpressed the SE produced approximately 2 times more GA molecules than the wild-type (WT) strain. Moreover, SE overexpression upregulated lanosterol synthase gene expression in the biosynthetic pathway. These results indicated that SE stimulates GA accumulation. Then, the SE and 3-hydroxy-3-methylglutaryl coenzyme A (HMGR) genes were simultaneously overexpressed in G. lingzhi. Compared with the individual overexpression of SE or HMGR, the combined overexpression of the two genes further enhanced individual GA production. The overexpressing strain produced maximum GA-T, GA-S, GA-Mk, and GA-Me contents of 90.4 ± 7.5, 35.9 ± 5.4, 6.2 ± 0.5, and 61.8 ± 5.8 μg/100 mg dry weight, respectively. These values were 5.9, 4.5, 2.4, and 5.8 times higher than those produced by the WT strain. This is the first example of the successful manipulation of multiple biosynthetic genes to improve GA content in G. lingzhi.

  17. Chronic alcoholism in rats induces a compensatory response, preserving brain thiamine diphosphate, but the brain 2-oxo acid dehydrogenases are inactivated despite unchanged coenzyme levels.

    Science.gov (United States)

    Parkhomenko, Yulia M; Kudryavtsev, Pavel A; Pylypchuk, Svetlana Yu; Chekhivska, Lilia I; Stepanenko, Svetlana P; Sergiichuk, Andrej A; Bunik, Victoria I

    2011-06-01

    Thiamine-dependent changes in alcoholic brain were studied using a rat model. Brain thiamine and its mono- and diphosphates were not reduced after 20 weeks of alcohol exposure. However, alcoholism increased both synaptosomal thiamine uptake and thiamine diphosphate synthesis in brain, pointing to mechanisms preserving thiamine diphosphate in the alcoholic brain. In spite of the unchanged level of the coenzyme thiamine diphosphate, activities of the mitochondrial 2-oxoglutarate and pyruvate dehydrogenase complexes decreased in alcoholic brain. The inactivation of pyruvate dehydrogenase complex was caused by its increased phosphorylation. The inactivation of 2-oxoglutarate dehydrogenase complex (OGDHC) correlated with a decrease in free thiols resulting from an elevation of reactive oxygen species. Abstinence from alcohol following exposure to alcohol reactivated OGDHC along with restoration of the free thiol content. However, restoration of enzyme activity occurred before normalization of reactive oxygen species levels. Hence, the redox status of cellular thiols mediates the action of oxidative stress on OGDHC in alcoholic brain. As a result, upon chronic alcohol consumption, physiological mechanisms to counteract the thiamine deficiency and silence pyruvate dehydrogenase are activated in rat brain, whereas OGDHC is inactivated due to impaired antioxidant ability. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  18. ORF Alignment: NC_002945 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available ] ... pdb|1M4I|B Chain B, Aminoglycoside ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis...ain A, Aminoglycoside ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis-Complex W...se From Mycobacterium ... Tuberculosis-Complex With Coenzyme A And Ribostamycin ... pdb|1M4G|A... Chain A, Aminoglycoside ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis... ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis-Complex With Coenzyme A And Tob

  19. ORF Alignment: NC_000962 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available ] ... pdb|1M4I|B Chain B, Aminoglycoside ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis...ain A, Aminoglycoside ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis-Complex W...se From Mycobacterium ... Tuberculosis-Complex With Coenzyme A And Ribostamycin ... pdb|1M4G|A... Chain A, Aminoglycoside ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis... ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis-Complex With Coenzyme A And Tob

  20. ORF Alignment: NC_002755 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available ] ... pdb|1M4I|B Chain B, Aminoglycoside ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis...ain A, Aminoglycoside ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis-Complex W...se From Mycobacterium ... Tuberculosis-Complex With Coenzyme A And Ribostamycin ... pdb|1M4G|A... Chain A, Aminoglycoside ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis... ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis-Complex With Coenzyme A And Tob

  1. Supplementation with Selenium and Coenzyme Q10 Reduces Cardiovascular Mortality in Elderly with Low Selenium Status. A Secondary Analysis of a Randomised Clinical Trial

    Science.gov (United States)

    Alexander, Jan; Aaseth, Jan

    2016-01-01

    Background Selenium is needed by all living cells in order to ensure the optimal function of several enzyme systems. However, the selenium content in the soil in Europe is generally low. Previous reports indicate that a dietary supplement of selenium could reduce cardiovascular disease but mainly in populations in low selenium areas. The objective of this secondary analysis of a previous randomised double-blind placebo-controlled trial from our group was to determine whether the effects on cardiovascular mortality of supplementation with a fixed dose of selenium and coenzyme Q10 combined during a four-year intervention were dependent on the basal level of selenium. Methods In 668 healthy elderly individuals from a municipality in Sweden, serum selenium concentration was measured. Of these, 219 individuals received daily supplementation with selenium (200 μg Se as selenized yeast) and coenzyme Q10 (200 mg) combined for four years. The remaining participants (n = 449) received either placebo (n = 222) or no treatment (n = 227). All cardiovascular mortality was registered. No participant was lost during a median follow-up of 5.2 years. Based on death certificates and autopsy results, all mortality was registered. Findings The mean serum selenium concentration among participants at baseline was low, 67.1 μg/L. Based on the distribution of selenium concentration at baseline, the supplemented group was divided into three groups; 85 μg/L (45 and 90 percentiles) and the remaining participants were distributed accordingly. Among the non-treated participants, lower cardiovascular mortality was found in the high selenium group as compared with the low selenium group (13.0% vs. 24.1%; P = 0.04). In the group with the lowest selenium basal concentration, those receiving placebo or no supplementation had a mortality of 24.1%, while mortality was 12.1% in the group receiving the active substance, which was an absolute risk reduction of 12%. In the middle selenium concentration

  2. Effects of coenzyme Q10 supplementation on plasma C-reactive protein concentrations: A systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Mazidi, Mohsen; Kengne, Andre Pascal; Banach, Maciej

    2018-02-01

    The aim of this systematic review and meta-analysis of prospective interventional studies was to investigate the effects of coenzyme Q10 (CQ10) on plasma C-reactive protein (CRP) levels. PubMed/Medline, Web of Science (WoS), Cochrane Database and Google Scholar databases were searched (up to December 2016) to identify prospective studies evaluating the impact of CQ10 supplementation on CRP. Random effects models meta-analysis was used for quantitative data synthesis. Sensitivity analysis used the leave-one-out method, and heterogeneity was quantitatively assessed using the I 2 index. Systematic review PROSPERO database registration: CRD42016038155. From a total of 119 entries identified via searches, 7 studies were finally included to the analysis. The results of the meta-analysis indicated a non-significant reduction in CRP concentrations following supplementation with CQ10 with a weighted mean difference [WMD] of -0.25mg/l (95% confidence intervals [CI] -0.56 to 0.06, I 2 =42.0%). The WMD for the effects on interleukin 6 (IL6) was -0.72pg/dl, (95% CI -1.24 to -0.24, I 2 =51.8%). These findings were robust in sensitivity analyses. Random-effects meta-regression revealed that changes in plasma CRP levels were independent of the dosage of CQ10 (slope: -0.0005; 95% CI: -0.005, 0.004; p=0.832) while duration of supplementation was the dependent mediator (slope: slope: -0.111; 95% CI: -0.21, -0.004; p=0.042). In conclusion, CQ10 supplementation has a borderline favourable effect on CRP levels, and a significant effect on IL-6 level. This suggests that CQ10 supplementation likely attenuates subclinical inflammation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. OleA Glu117 is key to condensation of two fatty-acyl coenzyme A substrates in long-chain olefin biosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, Matthew R.; Goblirsch, Brandon R.; Christenson, James K.; Esler, Morgan A.; Mohamed, Fatuma A.; Wackett, Lawrence P.; Wilmot, Carrie M. (UMM)

    2017-10-12

    In the interest of decreasing dependence on fossil fuels, microbial hydrocarbon biosynthesis pathways are being studied for renewable, tailored production of specialty chemicals and biofuels. One candidate is long-chain olefin biosynthesis, a widespread bacterial pathway that produces waxy hydrocarbons. Found in three- and four-gene clusters, oleABCD encodes the enzymes necessary to produce cis-olefins that differ by alkyl chain length, degree of unsaturation, and alkyl chain branching. The first enzyme in the pathway, OleA, catalyzes the Claisen condensation of two fatty acyl-coenzyme A (CoA) molecules to form a β-keto acid. In this report, the mechanistic role of Xanthomonas campestris OleA Glu117 is investigated through mutant enzymes. Crystal structures were determined for each mutant as well as their complex with the inhibitor cerulenin. Complemented by substrate modeling, these structures suggest that Glu117 aids in substrate positioning for productive carbon–carbon bond formation. Analysis of acyl-CoA substrate hydrolysis shows diminished activity in all mutants. When the active site lacks an acidic residue in the 117 position, OleA cannot form condensed product, demonstrating that Glu117 has a critical role upstream of the essential condensation reaction. Profiling of pH dependence shows that the apparent pKa for Glu117 is affected by mutagenesis. Taken together, we propose that Glu117 is the general base needed to prime condensation via deprotonation of the second, non-covalently bound substrate during turnover. This is the first example of a member of the thiolase superfamily of condensing enzymes to contain an active site base originating from the second monomer of the dimer.

  4. High-yield production of vanillin from ferulic acid by a coenzyme-independent decarboxylase/oxygenase two-stage process.

    Science.gov (United States)

    Furuya, Toshiki; Miura, Misa; Kuroiwa, Mari; Kino, Kuniki

    2015-05-25

    Vanillin is one of the world's most important flavor and fragrance compounds in foods and cosmetics. Recently, we demonstrated that vanillin could be produced from ferulic acid via 4-vinylguaiacol in a coenzyme-independent manner using the decarboxylase Fdc and the oxygenase Cso2. In this study, we investigated a new two-pot bioprocess for vanillin production using the whole-cell catalyst of Escherichia coli expressing Fdc in the first stage and that of E. coli expressing Cso2 in the second stage. We first optimized the second-step Cso2 reaction from 4-vinylguaiacol to vanillin, a rate-determining step for the production of vanillin. Addition of FeCl2 to the cultivation medium enhanced the activity of the resulting E. coli cells expressing Cso2, an iron protein belonging to the carotenoid cleavage oxygenase family. Furthermore, a butyl acetate-water biphasic system was effective in improving the production of vanillin. Under the optimized conditions, we attempted to produce vanillin from ferulic acid by a two-pot bioprocess on a flask scale. In the first stage, E. coli cells expressing Fdc rapidly decarboxylated ferulic acid and completely converted 75 mM of this substrate to 4-vinylguaiacol within 2 h at pH 9.0. After the first-stage reaction, cells were removed from the reaction mixture by centrifugation, and the pH of the resulting supernatant was adjusted to 10.5, the optimal pH for Cso2. This solution was subjected to the second-stage reaction. In the second stage, E. coli cells expressing Cso2 efficiently oxidized 4-vinylguaiacol to vanillin. The concentration of vanillin reached 52 mM (7.8 g L(-1)) in 24 h, which is the highest level attained to date for the biotechnological production of vanillin using recombinant cells. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney disease.

    Science.gov (United States)

    Barden, Anne E; Shinde, Sujata; Burke, Valerie; Puddey, Ian B; Beilin, Lawrence J; Irish, Ashley B; Watts, Gerald F; Mori, Trevor A

    2018-03-22

    Neutrophils release leukotriene (LT)B 4 and myeloperoxidase (MPO) that may be important mediators of chronic inflammation in chronic kidney disease (CKD). The n-3 fatty acids (n-3 FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have the potential to attenuate inflammation through production of LTB 5 and the Specialized Proresolving Lipid Mediators (SPM) that promote the resolution of inflammation. In animal models, coenzyme Q10 (CoQ) also attenuates inflammation by reducing MPO and LTB 4 . This study evaluated the independent and combined effects of n-3 FA and CoQ supplementation on neutrophil leukotrienes, the pro-inflammatory eicosanoid 5-hydroxyeicosatetraenoic acid (5-HETE), SPM, and plasma MPO, in patients with CKD. In a double-blind, placebo-controlled intervention of factorial design, 85 patients with CKD were randomized to either n-3 FA (4 g), CoQ (200 mg), both supplements, or control (4 g olive oil), daily for 8 weeks. Plasma MPO and calcium ionophore-stimulated neutrophil release of LTs, 5-HETE and SPM were measured at baseline and after 8 weeks. Seventy four patients completed the intervention. n-3 FA, but not CoQ, significantly increased neutrophil LTB 5 (P n-3 FA or CoQ. Plasma MPO was significantly reduced with n-3 FA alone (P = 0.013) but not when given in combination with CoQ. n-3 FA supplementation in patients with CKD leads to increased neutrophil release of LTB 5 and several SPM, as well as a reduction in plasma MPO that may have important implications for limiting chronic inflammation. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. The effects of coenzyme Q10 treatment on maternally inherited diabetes mellitus and deafness, and mitochondrial DNA 3243 (A to G) mutation.

    Science.gov (United States)

    Suzuki, S; Hinokio, Y; Ohtomo, M; Hirai, M; Hirai, A; Chiba, M; Kasuga, S; Satoh, Y; Akai, H; Toyota, T

    1998-05-01

    The characteristic clinical features of diabetes mellitus with mitochondrial DNA (mtDNA) 3243(A-G) mutation are progressive insulin secretory defect, neurosensory deafness and maternal inheritance, referred to as maternally inherited diabetes mellitus and deafness (MIDD). A treatment for MIDD to improve insulin secretory defects and reduce deafness has not been established. The effects of coenzyme Q10 (CoQ10) treatment on insulin secretory response, hearing capacity and clinical symptoms of MIDD were investigated. 28 MIDD patients (CoQ10-DM), 7 mutant subjects with impaired glucose tolerance (IGT), and 15 mutant subjects with normal glucose tolerance (NGT) were treated daily with oral administration of 150 mg of CoQ10 for 3 years. Insulin secretory response, blood lactate after exercise, hearing capacity and other laboratory examinations were investigated every year. In the same way we evaluated 16 MIDD patients (control-DM), 5 mutant IGT and 5 mutant NGT subjects in yearly examinations. The insulin secretory response assessed by glucagon-induced C-peptide secretion and 24 h urinary C-peptide excretion after 3 years in the CoQ10-DM group was significantly higher than that in the control-DM group. CoQ10 therapy prevented progressive hearing loss and improved blood lactate after exercise in the MIDD patients. CoQ10 treatment did not affect the diabetic complications or other clinical symptoms of MIDD patients. CoQ10 treatment did not affect the insulin secretory capacity of the mutant IGT and NGT subjects. There were no side effects during therapy. This is the first report demonstrating the therapeutic usefulness of CoQ10 on MIDD.

  7. Liquid chromatography-tandem mass spectrometry method for the measurement of serum mevalonic acid: a novel marker of hydroxymethylglutaryl coenzyme A reductase inhibition by statins.

    Science.gov (United States)

    Waldron, Jenna; Webster, Craig

    2011-05-01

    Mevalonic acid (MVA) is synthesized at an early and rate-limiting step in the biosynthesis of cholesterol by the enzyme hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, and is a useful measure of statin efficacy or treatment. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the measurement of serum MVA has been developed. Following the in vitro conversion of MVA to mevalonic acid lactone (MVAL) in the serum, MVAL and a deuterated internal standard were extracted using an online solid-phase extraction procedure. Chromatographic separation was achieved using a Luna PFP column (Phenomenex), with enhanced selectivity and improved resolution for polar compounds. A gradient system was used, with mobile phase comprising methanol and water (5 mmol/L ammonium formate buffer, pH 2.5). Analysis was performed using an API 5000 tandem mass spectrometer (Applied Biosystems) in positive electrospray ionization mode. The method showed excellent recoveries (98 ± 8%) and imprecision (intra-assay coefficient of variation of 2.2% [6.5 ng/mL] and 2.6% [10.5 ng/mL], and inter-assay coefficient of variation of 9% [10.5 ng/mL]). The assay provides a calibration range up to 50 ng/mL with a limit of detection at 0.1 ng/mL. A simple, rapid and analytically specific method has been developed for the measurement of serum MVA, in the form of MVAL. The high analytical sensitivity of the method allows for accurate quantitation of MVAL in serum samples, both at the endogenous levels found in healthy individuals and in statin-treated patients where normal levels are expected to be greatly reduced through the inhibition of HMG-CoA reductase.

  8. Efficacy of eyedrops containing cross-linked hyaluronic acid and coenzyme Q10 in treating patients with mild to moderate dry eye.

    Science.gov (United States)

    Postorino, Elisa I; Rania, Laura; Aragona, Emanuela; Mannucci, Carmen; Alibrandi, Angela; Calapai, Gioacchino; Puzzolo, Domenico; Aragona, Pasquale

    2018-01-01

    Dry eye disease (DED) is a common condition causing substantial burden. A randomized, controlled, single-masked study was performed in 40 patients with mild to moderate DED to evaluate the efficacy and safety of a collyrium based on crosslinked hyaluronic acid (XLHA) with coenzyme Q10 (CoQ10). Enrolled subjects were divided into 2 groups: group A, treated with XLHA + CoQ10; and group B, treated with hyaluronic acid (HA). Eyedrops were administered 4 times daily for 3 months. The Ocular Surface Disease Index (OSDI) questionnaire, tear break-up time (TBUT), corneal and conjunctival staining, and meibomian gland assessment (MGD) were evaluated; furthermore, corneal aesthesiometry, in vivo corneal confocal microscopy, visual acuity, intraocular pressure (IOP), and fundus examination were performed. At the end of treatment, OSDI score significantly decreased in groups A and B (p<0.01 and p<0.05, respectively); the decrease was significantly higher in group A. Corneal staining decreased in both groups, with lower scores in group A. The MGD was significantly ameliorated in group A patients. No differences were found for corneal aesthesiometry or TBUT. Epithelial cell reflectivity was significantly reduced only in group A. For keratocytes and stromal matrix parameters, there was a significant improvement in group A. No changes were found for visual acuity, IOP, or fundus examination. The XLHA + CoQ10 treatment showed greater effectiveness in DED compared to HA alone, probably due to the longer permanency on ocular surface and the antioxidant activity of CoQ10. Therefore, XLHA + CoQ10 eyedrops could represent a new possibility in dry eye treatment.

  9. Anaerobic p-coumarate degradation by Rhodopseudomonas palustris and identification of CouR, a MarR repressor protein that binds p-coumaroyl coenzyme A.

    Science.gov (United States)

    Hirakawa, Hidetada; Schaefer, Amy L; Greenberg, E Peter; Harwood, Caroline S

    2012-04-01

    The phenylpropanoid p-coumarate and structurally related aromatic compounds are produced in large amounts by green plants and are excellent carbon sources for many soil bacteria. Aerobic bacteria remove the acyl side chain from phenylpropanoids to leave an aromatic aldehyde, which then enters one of several possible central pathways of benzene ring degradation. We investigated the pathway for the anaerobic degradation of p-coumarate by the phototrophic bacterium Rhodopseudomonas palustris and found that it also follows this metabolic logic. We characterized enzymes for the conversion of p-coumarate to p-hydroxybenzaldehyde and acetyl coenzyme A (acetyl-CoA) encoded by the couAB operon. We also identified a MarR family transcriptional regulator that we named CouR. A couR mutant had elevated couAB expression. In addition, His-tagged CouR bound with high affinity to a DNA fragment encompassing the couAB promoter region, and binding was abrogated by the addition of nanomolar quantities of p-coumaroyl-CoA but not by p-coumarate. Footprinting demonstrated binding of CouR to an inverted repeat sequence that overlaps the -10 region of the couAB promoter. Our results provide evidence for binding of a CoA-modified aromatic compound by a MarR family member. Although the MarR family is widely distributed in bacteria and archaea and includes over 12,000 members, ligands have been identified for relatively few family members. Here we provide biochemical evidence for a new category of MarR ligand.

  10. Association of Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies With DRB1*07:01 and Severe Myositis in Juvenile Myositis Patients.

    Science.gov (United States)

    Kishi, Takayuki; Rider, Lisa G; Pak, Katherine; Barillas-Arias, Lilliana; Henrickson, Michael; McCarthy, Paul L; Shaham, Bracha; Weiss, Pamela F; Horkayne-Szakaly, Iren; Targoff, Ira N; Miller, Frederick W; Mammen, Andrew L

    2017-07-01

    Autoantibodies recognizing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) are associated with statin exposure, the HLA allele DRB1*11:01, and necrotizing muscle biopsies in adult myositis patients. The aim of this study was to characterize the features of juvenile anti-HMGCR-positive myositis patients. The sera of 440 juvenile myositis patients were screened for anti-HMGCR autoantibodies. Demographic and clinical features, responses to therapy, and HLA alleles were assessed. The features of anti-HMGCR-positive patients were compared to those of previously described adult patients with this autoantibody and to children with other myositis-specific autoantibodies (MSAs). Five of 440 patients (1.1%) were anti-HMGCR-positive; none had taken statin medications. Three patients had rashes characteristic of juvenile dermatomyositis and 2 patients had immune-mediated necrotizing myopathies. The median highest creatine kinase (CK) level of anti-HMGCR-positive subjects was 17,000 IU/liter. All patients had severe proximal muscle weakness, distal weakness, muscle atrophy, joint contractures, and arthralgias, which were all more prevalent in HMGCR-positive subjects compared to MSA-negative patients or those with other MSAs. Anti-HMGCR-positive patients had only partial responses to multiple immunosuppressive medications, and their disease often took a chronic course. The DRB1*07:01 allele was present in all 5 patients, compared to 26.25% of healthy controls (corrected P = 0.01); none of the 5 juvenile patients had DRB1*11:01. Compared to children with other MSAs, muscle disease appears to be more severe in those with anti-HMGCR autoantibodies. Like adults, children with anti-HMGCR autoantibodies have severe weakness and high CK levels. In contrast to adults, in anti-HMGCR-positive children, there is a strong association with HLA-DRB1*07:01. © 2017, American College of Rheumatology.

  11. The effect of short-term coenzyme Q10 supplementation and pre-cooling strategy on cardiac damage markers in elite swimmers.

    Science.gov (United States)

    Emami, Ali; Tofighi, Asghar; Asri-Rezaei, Siamak; Bazargani-Gilani, Behnaz

    2018-02-01

    Strenuous physical exercise and hyperthermia may paradoxically induce oxidative stress and adverse effects on myocardial function. The purpose of this study was to investigate the effect of 14-d coenzyme Q10 (CoQ10) supplementation and pre-cooling on serum creatine kinase-MB (CK-MB), cardiac Troponin I (cTnI), myoglobin (Mb), lactate dehydrogenase (LD), total antioxidant capacity (TAC), lipid peroxidation (LPO) and CoQ10 concentration in elite swimmers. In total, thirty-six healthy males (mean age 17 (sd 1) years) were randomly selected and divided into four groups of supplementation, supplementation with pre-cooling, pre-cooling and control. During an eighteen-session protocol in the morning and evening, subjects attended speed and endurance swimming training sessions for 5 km in each session. Blood sampling was done before (two stages) and after (two stages) administration of CoQ10 and pre-cooling. ANCOVA and repeated measurement tests with Bonferroni post hoc test were used for the statistical analysis of the data. There was no significant statistical difference among groups for the levels of CK-MB, cTnI, Mb, LD, TAC, LPO and CoQ10 at the presampling (stages 1 and 2) (P>0·05). However, pre-cooling and control groups show a significant increase in the levels of CK-MB, cTnI, Mb, LD and LPO compared with the supplementation and supplementation with pre-cooling groups in the post-sampling (stages 1 and 2) (Pcompetition phase. Meanwhile, the pre-cooling strategy individually has no desired effect on the levels of CK-MB, cTnI, Mb, LD, LPO, TAC and CoQ10.

  12. Cloning, Expression Profiling and Functional Analysis of CnHMGS, a Gene Encoding 3-hydroxy-3-Methylglutaryl Coenzyme A Synthase from Chamaemelum nobile

    Directory of Open Access Journals (Sweden)

    Shuiyuan Cheng

    2016-03-01

    Full Text Available Roman chamomile (Chamaemelum nobile L. is renowned for its production of essential oils, which major components are sesquiterpenoids. As the important enzyme in the sesquiterpenoid biosynthesis pathway, 3-hydroxy-3-methylglutaryl coenzyme A synthase (HMGS catalyze the crucial step in the mevalonate pathway in plants. To isolate and identify the functional genes involved in the sesquiterpene biosynthesis of C. nobile L., a HMGS gene designated as CnHMGS (GenBank Accession No. KU529969 was cloned from C. nobile. The cDNA sequence of CnHMGS contained a 1377 bp open reading frame encoding a 458-amino-acid protein. The sequence of the CnHMGS protein was highly homologous to those of HMGS proteins from other plant species. Phylogenetic tree analysis revealed that CnHMGS clustered with the HMGS of Asteraceae in the dicotyledon clade. Further functional complementation of CnHMGS in the mutant yeast strain YSC6274 lacking HMGS activity demonstrated that the cloned CnHMGS cDNA encodes a functional HMGS. Transcript profile analysis indicated that CnHMGS was preferentially expressed in flowers and roots of C. nobile. The expression of CnHMGS could be upregulated by exogenous elicitors, including methyl jasmonate and salicylic acid, suggesting that CnHMGS was elicitor-responsive. The characterization and expression analysis of CnHMGS is helpful to understand the biosynthesis of sesquiterpenoid in C. nobile at the molecular level and also provides molecular wealth for the biotechnological improvement of this important medicinal plant.

  13. Inhibition of liver fibrosis by solubilized coenzyme Q10: Role of Nrf2 activation in inhibiting transforming growth factor-β1 expression

    International Nuclear Information System (INIS)

    Choi, Hoo-Kyun; Pokharel, Yuba Raj; Lim, Sung Chul; Han, Hyo-Kyung; Ryu, Chang Seon; Kim, Sang Kyum; Kwak, Mi Kyong; Kang, Keon Wook

    2009-01-01

    Coenzyme Q10 (CoQ10), an endogenous antioxidant, is important in oxidative phosphorylation in mitochondria. It has anti-diabetic and anti-cardiovascular disease effects, but its ability to protect against liver fibrosis has not been studied. Here, we assessed the ability of solubilized CoQ10 to improve dimethylnitrosamine (DMN)-induced liver fibrogenesis in mice. DMN treatments for 3 weeks produced a marked liver fibrosis as assessed by histopathological examination and tissue 4-hydroxyproline content. Solubilized CoQ10 (10 and 30 mg/kg) significantly inhibited both the increases in fibrosis score and 4-hydroxyproline content induced by DMN. Reverse transcription-polymerase chain reaction and Western blot analyses revealed that solubilized CoQ10 inhibited increases in the transforming growth factor-β1 (TGF-β1) mRNA and α-smooth muscle actin (α-SMA) protein by DMN. Interestingly, hepatic glutamate-cysteine ligase (GCL) and glutathione S-transferase A2 (GSTA2) were up-regulated in mice treated with CoQ10. Solubilized CoQ10 also up-regulated antioxidant enzymes such as catalytic subunits of GCL and GSTA2 via activating NF-E2 related factor2 (Nrf2)/antioxidant response element (ARE) in H4IIE hepatoma cells. Moreover, CoQ10's inhibition of α-SMA and TGF-β1 expressions disappeared in Nrf2-null MEF cells. In contrast, Nrf2 overexpression significantly decreased the basal expression levels of α-SMA and TGF-β1 in Nrf2-null MEF cells. These results demonstrated that solubilized CoQ10 inhibited DMN-induced liver fibrosis through suppression of TGF-β1 expression via Nrf2/ARE activation.

  14. Pilot study of safety and efficacy of polyprenols in combination with coenzyme Q10 in patients with statin-induced myopathy.

    Science.gov (United States)

    Latkovskis, Gustavs; Saripo, Vita; Sokolova, Emma; Upite, Dana; Vanaga, Ilona; Kletnieks, Ugis; Erglis, Andrejs

    2016-01-01

    Statin-induced myopathy (SIM) has been partially attributed to deficiency of dolichol and coenzyme Q10 (CoQ10). We aimed to test the safety and efficacy of plant polyprenols in combination with CoQ10 for alleviation of SIM. In an open-label, one-center prospective pilot study patients with SIM received conifer-tree needle polyprenols (4mg/day) and CoQ10 (100mg/day) for 8 weeks. Symptoms and safety were evaluated according to symptom severity score (0-10), creatine kinase (CK) levels, exercise test, dynamometry, complete blood count, clinical biochemistry and electrocardiography. Of the 14 patients, 11 completed the study per protocol. Two patients withdrew consent due to travels abroad, and it was discontinued for one patient with stage 3 chronic kidney disease due to asymptomatic elevations of liver enzymes at week 4. No safety parameters changed significantly in per protocol group. Non-significant increase of CK levels was observed (P=0.231). Muscle pain (n=10) and weakness (n=7) scores improved significantly (PMuscle pain completely disappeared in 2 patients, weakness resolved in 3 patients and cramps disappeared in two patients. Four patients assessed improvement strong enough to consider increase of statin dose. No changes were observed in exercise test or dynamometry. Conifer-tree polyprenols in combination with CoQ10 may be generally safe in patients with SIM, but caution should be exercised in patients with glomerular filtration rate <60mL/min and routine monitoring of the liver enzymes and CK is advocated in all patients. The observed efficacy provides the rationale for a larger, double-blind controlled study with polyprenols. Copyright © 2016 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  15. Cardiac dysfunction and peri-weaning mortality in malonyl-coenzyme A decarboxylase (MCD) knockout mice as a consequence of restricting substrate plasticity.

    Science.gov (United States)

    Aksentijević, Dunja; McAndrew, Debra J; Karlstädt, Anja; Zervou, Sevasti; Sebag-Montefiore, Liam; Cross, Rebecca; Douglas, Gillian; Regitz-Zagrosek, Vera; Lopaschuk, Gary D; Neubauer, Stefan; Lygate, Craig A

    2014-10-01

    Inhibition of malonyl-coenzyme A decarboxylase (MCD) shifts metabolism from fatty acid towards glucose oxidation, which has therapeutic potential for obesity and myocardial ischemic injury. However, ~40% of patients with MCD deficiency are diagnosed with cardiomyopathy during infancy. To clarify the link between MCD deficiency and cardiac dysfunction in early life and to determine the contributing systemic and cardiac metabolic perturbations. MCD knockout mice ((-/-)) exhibited non-Mendelian genotype ratios (31% fewer MCD(-/-)) with deaths clustered around weaning. Immediately prior to weaning (18days) MCD(-/-) mice had lower body weights, elevated body fat, hepatic steatosis and glycogen depletion compared to wild-type littermates. MCD(-/-) plasma was hyperketonemic, hyperlipidemic, had 60% lower lactate levels and markers of cellular damage were elevated. MCD(-/-) hearts exhibited hypertrophy, impaired ejection fraction and were energetically compromised (32% lower total adenine nucleotide pool). However differences between WT and MCD(-/-) converged with age, suggesting that, in surviving MCD(-/-) mice, early cardiac dysfunction resolves over time. These observations were corroborated by in silico modelling of cardiomyocyte metabolism, which indicated improvement of the MCD(-/-) metabolic phenotype and improved cardiac efficiency when switched from a high-fat diet (representative of suckling) to a standard post-weaning diet, independent of any developmental changes. MCD(-/-) mice consistently exhibited cardiac dysfunction and severe metabolic perturbations while on a high-fat, low carbohydrate diet of maternal milk and these gradually resolved post-weaning. This suggests that dysfunction is a common feature of MCD deficiency during early development, but that severity is dependent on composition of dietary substrates. Copyright © 2014. Published by Elsevier Ltd.

  16. Genome-Wide Identification and Comparative Analysis of the 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase (HMGR Gene Family in Gossypium

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    Wei Liu

    2018-01-01

    Full Text Available Terpenes are the largest and most diverse class of secondary metabolites in plants and play a very important role in plant adaptation to environment. 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR is a rate-limiting enzyme in the process of terpene biosynthesis in the cytosol. Previous study found the HMGR genes underwent gene expansion in Gossypium raimondii, but the characteristics and evolution of the HMGR gene family in Gossypium genus are unclear. In this study, genome-wide identification and comparative study of HMGR gene family were carried out in three Gossypium species with genome sequences, i.e., G. raimondii, Gossypium arboreum, and Gossypium hirsutum. In total, nine, nine and 18 HMGR genes were identified in G. raimondii, G. arboreum, and G. hirsutum, respectively. The results indicated that the HMGR genes underwent gene expansion and a unique gene cluster containing four HMGR genes was found in all the three Gossypium species. The phylogenetic analysis suggested that the expansion of HMGR genes had occurred in their common ancestor. There was a pseudogene that had a 10-bp deletion resulting in a frameshift mutation and could not be translated into functional proteins in G. arboreum and the A-subgenome of G. hirsutum. The expression profiles of the two pseudogenes showed that they had tissue-specific expression. Additionally, the expression pattern of the pseudogene in the A-subgenome of G. hirsutum was similar to its paralogous gene in the D-subgenome of G. hirsutum. Our results provide useful information for understanding cytosolic terpene biosynthesis in Gossypium species.

  17. Modification of the Host Cell Lipid Metabolism Induced by Hypolipidemic Drugs Targeting the Acetyl Coenzyme A Carboxylase Impairs West Nile Virus Replication.

    Science.gov (United States)

    Merino-Ramos, Teresa; Vázquez-Calvo, Ángela; Casas, Josefina; Sobrino, Francisco; Saiz, Juan-Carlos; Martín-Acebes, Miguel A

    2016-01-01

    West Nile virus (WNV) is a neurotropic flavivirus transmitted by the bite of mosquitoes that causes meningitis and encephalitis in humans, horses, and birds. Several studies have highlighted that flavivirus infection is highly dependent on cellular lipids for virus replication and infectious particle biogenesis. The first steps of lipid synthesis involve the carboxylation of acetyl coenzyme A (acetyl-CoA) to malonyl-CoA that is catalyzed by the acetyl-CoA carboxylase (ACC). This makes ACC a key enzyme of lipid synthesis that is currently being evaluated as a therapeutic target for different disorders, including cancers, obesity, diabetes, and viral infections. We have analyzed the effect of the ACC inhibitor 5-(tetradecyloxy)-2-furoic acid (TOFA) on infection by WNV. Lipidomic analysis of TOFA-treated cells confirmed that this drug reduced the cellular content of multiple lipids, including those directly implicated in the flavivirus life cycle (glycerophospholipids, sphingolipids, and cholesterol). Treatment with TOFA significantly inhibited the multiplication of WNV in a dose-dependent manner. Further analysis of the antiviral effect of this drug showed that the inhibitory effect was related to a reduction of viral replication. Furthermore, treatment with another ACC inhibitor, 3,3,14,14-tetramethylhexadecanedioic acid (MEDICA 16), also inhibited WNV infection. Interestingly, TOFA and MEDICA 16 also reduced the multiplication of Usutu virus (USUV), a WNV-related flavivirus. These results point to the ACC as a druggable cellular target suitable for antiviral development against WNV and other flaviviruses. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  18. A conserved START domain coenzyme Q-binding polypeptide is required for efficient Q biosynthesis, respiratory electron transport, and antioxidant function in Saccharomyces cerevisiae.

    Science.gov (United States)

    Allan, Christopher M; Hill, Shauna; Morvaridi, Susan; Saiki, Ryoichi; Johnson, Jarrett S; Liau, Wei-Siang; Hirano, Kathleen; Kawashima, Tadashi; Ji, Ziming; Loo, Joseph A; Shepherd, Jennifer N; Clarke, Catherine F

    2013-04-01

    Coenzyme Qn (ubiquinone or Qn) is a redox active lipid composed of a fully substituted benzoquinone ring and a polyisoprenoid tail of n isoprene units. Saccharomyces cerevisiae coq1-coq9 mutants have defects in Q biosynthesis, lack Q6, are respiratory defective, and sensitive to stress imposed by polyunsaturated fatty acids. The hallmark phenotype of the Q-less yeast coq mutants is that respiration in isolated mitochondria can be rescued by the addition of Q2, a soluble Q analog. Yeast coq10 mutants share each of these phenotypes, with the surprising exception that they continue to produce Q6. Structure determination of the Caulobacter crescentus Coq10 homolog (CC1736) revealed a steroidogenic acute regulatory protein-related lipid transfer (START) domain, a hydrophobic tunnel known to bind specific lipids in other START domain family members. Here we show that purified CC1736 binds Q2, Q3, Q10, or demethoxy-Q3 in an equimolar ratio, but fails to bind 3-farnesyl-4-hydroxybenzoic acid, a farnesylated analog of an early Q-intermediate. Over-expression of C. crescentus CC1736 or COQ8 restores respiratory electron transport and antioxidant function of Q6 in the yeast coq10 null mutant. Studies with stable isotope ring precursors of Q reveal that early Q-biosynthetic intermediates accumulate in the coq10 mutant and de novo Q-biosynthesis is less efficient than in the wild-type yeast or rescued coq10 mutant. The results suggest that the Coq10 polypeptide:Q (protein:ligand) complex may serve essential functions in facilitating de novo Q biosynthesis and in delivering newly synthesized Q to one or more complexes of the respiratory electron transport chain. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Pretreatment with coenzyme Q10 improves ovarian response and embryo quality in low-prognosis young women with decreased ovarian reserve: a randomized controlled trial.

    Science.gov (United States)

    Xu, Yangying; Nisenblat, Victoria; Lu, Cuiling; Li, Rong; Qiao, Jie; Zhen, Xiumei; Wang, Shuyu

    2018-03-27

    Management of women with reduced ovarian reserve or poor ovarian response (POR) to stimulation is one of the major challenges in reproductive medicine. The primary causes of POR remain elusive and oxidative stress was proposed as one of the important contributors. It has been suggested that focus on the specific subpopulations within heterogeneous group of poor responders could assist in evaluating optimal management strategies for these patients. This study investigated the effect of anti-oxidant treatment with coenzyme Q10 (CoQ10) on ovarian response and embryo quality in young low-prognosis patients with POR. This prospective, randomized controlled study included 186 consecutive patients with POR stratified according to the POSEIDON classification group 3 (age reserve parameters). The participants were randomized to the CoQ10 pre-treatment for 60 days preceding IVF-ICSI cycle or no pre-treatment. The number of high quality embryos was a primary outcome measure. A total of 169 participants were evaluated (76 treated with CoQ10 and 93 controls); 17 women were excluded due to low compliance with CoQ10 administration. The baseline demographic and clinical characteristics were comparable between the groups. CoQ10 pretreatment resulted in significantly lower gonadotrophin requirements and higher peak E2 levels. Women in CoQ10 group had increased number of retrieved oocytes (4, IQR 2-5), higher fertilization rate (67.49%) and more high-quality embryos (1, IQR 0-2); p reserve in IVF-ICSI cycles. Further work is required to determine whether there is an effect on clinical treatment endpoints.

  20. A single nucleotide polymorphism within the acetyl-coenzyme A carboxylase beta gene is associated with proteinuria in patients with type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Shiro Maeda

    2010-02-01

    Full Text Available It has been suggested that genetic susceptibility plays an important role in the pathogenesis of diabetic nephropathy. A large-scale genotyping analysis of gene-based single nucleotide polymorphisms (SNPs in Japanese patients with type 2 diabetes identified the gene encoding acetyl-coenzyme A carboxylase beta (ACACB as a candidate for a susceptibility to diabetic nephropathy; the landmark SNP was found in the intron 18 of ACACB (rs2268388: intron 18 +4139 C > T, p = 1.4x10(-6, odds ratio = 1.61, 95% confidence interval [CI]: 1.33-1.96. The association of this SNP with diabetic nephropathy was examined in 9 independent studies (4 from Japan including the original study, one Singaporean, one Korean, and two European with type 2 diabetes. One case-control study involving European patients with type 1 diabetes was included. The frequency of the T allele for SNP rs2268388 was consistently higher among patients with type 2 diabetes and proteinuria. A meta-analysis revealed that rs2268388 was significantly associated with proteinuria in Japanese patients with type 2 diabetes (p = 5.35 x 10(-8, odds ratio = 1.61, 95% Cl: 1.35-1.91. Rs2268388 was also associated with type 2 diabetes-associated end-stage renal disease (ESRD in European Americans (p = 6 x 10(-4, odds ratio = 1.61, 95% Cl: 1.22-2.13. Significant association was not detected between this SNP and nephropathy in those with type 1 diabetes. A subsequent in vitro functional analysis revealed that a 29-bp DNA fragment, including rs2268388, had significant enhancer activity in cultured human renal proximal tubular epithelial cells. Fragments corresponding to the disease susceptibility allele (T had higher enhancer activity than those of the major allele. These results suggest that ACACB is a strong candidate for conferring susceptibility for proteinuria in patients with type 2 diabetes.

  1. Properties of latent and thiol-activated rat hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase and regulation of enzyme activity.

    Science.gov (United States)

    Dotan, I; Shechter, I

    1983-10-15

    The effect of the thiols glutathione (GSH), dithiothreitol (DTT), and dithioerythritol (DTE) on the conversion of an inactive, latent form (El) of rat liver 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase, EC 1.1.1.34) to a catalyticaly active form (Ea) is examined. Latent hepatic microsomal HMG-CoA reductase is activated to a similar degree of activation by DTT and DTE and to a lower extent by GSH. All three thiols affect both Km and Vmax values of the enzyme toward HMG-CoA and NADPH. Studies of the effect of DTT on the affinity binding of HMG-CoA reductase to agarose-hexane-HMG-CoA (AG-HMG-CoA) resin shows that thiols are necessary for the binding of the enzyme to the resin. Removal of DTT from AG-HMG-CoA-bound soluble Ea (active enzyme) does not cause dissociation of the enzyme from the resin at low salt concentrations. Substitution of DTT by NADPH does not promote binding of soluble El (latent enzyme) to AG-HMG-CoA. The enzymatic activity of Ea in the presence of DTT and GSH indicates that these thiols compete for the same binding site on the enzyme. Diethylene glycol disulfide (ESSE) and glutathione disulfide (GSSG) inhibit the activity of Ea. ESSE is more effective for the inhibition of Ea than GSSG, causing a higher degree of maximal inhibition and affecting the enzymatic activity at lower concentrations. A method is described for the rapid conversion of soluble purified Ea to El using gel-filtration chromatography on Bio-Gel P-4 columns. These combined results point to the importance of the thiol/disulfide ratio for the modulation of hepatic HMG-CoA reductase activity.

  2. Modulatory role of Co-enzyme Q10 on methionine and choline deficient diet-induced non-alcoholic steatohepatitis (NASH) in albino rats.

    Science.gov (United States)

    Saleh, Dalia O; Ahmed, Rania F; Amin, Mohamed M

    2017-03-01

    The present study aimed to evaluate the hepato-protective and neuro-protective activity of Co-enzyme Q10 (CoQ10) on non-alcoholic steatohepatitis (NASH) in albino rats induced by methionine and choline-deficient (MCD) diet. Rats were fed an MCD diet for 8 weeks to induce non-alcoholic steatohepatitis. CoQ10 (10 mg/(kg·day) -1 ) was orally administered for 2 consecutive weeks. Twenty-four hours after the last dose of the drug, the behavioral test, namely the activity cage test, was performed and the activity counts were recorded. Serum alanine transaminase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, total/direct bilirubin, and albumin were valued to assess liver function. Moreover, hepatic cytokines interleukin-6 as well as its modulator nuclear factor kappa-light-chain-enhancer of activated B cells were determined. In addition, brain biomarkers, viz ammonia, nitric oxide, and brain-derived neurotrophic factor (BDNF), were measured as they are reliable indices to assess brain damage. Histopathological and immunohistochemical examination of brain proliferating cell nuclear antigen in brain and liver tissues were also evaluated. Results revealed that MCD-induced NASH showed impairment in the liver functions with an increase in the liver inflammatory markers. Moreover, NASH resulted in pronounced brain dysfunction as evidenced by hyper-locomotor activity, a decrease in the BDNF level, as well as an increase in the brain nitric oxide and ammonia contents. Oral treatment of MCD-diet-fed rats with CoQ10 for 14 days showed a marked improvement in all the assigned parameters. Finally, it can be concluded that CoQ10 has a hepatoprotective and neuroprotective role in MCD-diet-induced NASH in rats.

  3. Acetyl coenzyme A synthetase is acetylated on multiple lysine residues by a protein acetyltransferase with a single Gcn5-type N-acetyltransferase (GNAT) domain in Saccharopolyspora erythraea.

    Science.gov (United States)

    You, Di; Yao, Li-Li; Huang, Dan; Escalante-Semerena, Jorge C; Ye, Bang-Ce

    2014-09-01

    Reversible lysine acetylation (RLA) is used by cells of all domains of life to modulate protein function. To date, bacterial acetylation/deacetylation systems have been studied in a few bacteria (e.g., Salmonella enterica, Bacillus subtilis, Escherichia coli, Erwinia amylovora, Mycobacterium tuberculosis, and Geobacillus kaustophilus), but little is known about RLA in antibiotic-producing actinomycetes. Here, we identify the Gcn5-like protein acetyltransferase AcuA of Saccharopolyspora erythraea (SacAcuA, SACE_5148) as the enzyme responsible for the acetylation of the AMP-forming acetyl coenzyme A synthetase (SacAcsA, SACE_2375). Acetylated SacAcsA was deacetylated by a sirtuin-type NAD(+)-dependent consuming deacetylase (SacSrtN, SACE_3798). In vitro acetylation/deacetylation of SacAcsA enzyme was studied by Western blotting, and acetylation of lysine residues Lys(237), Lys(380), Lys(611), and Lys(628) was confirmed by mass spectrometry. In a strain devoid of SacAcuA, none of the above-mentioned Lys residues of SacAcsA was acetylated. To our knowledge, the ability of SacAcuA to acetylate multiple Lys residues is unique among AcuA-type acetyltransferases. Results from site-specific mutagenesis experiments showed that the activity of SacAcsA was controlled by lysine acetylation. Lastly, immunoprecipitation data showed that in vivo acetylation of SacAcsA was influenced by glucose and acetate availability. These results suggested that reversible acetylation may also be a conserved regulatory posttranslational modification strategy in antibiotic-producing actinomycetes. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  4. Induction of Neuron-Specific Degradation of Coenzyme A Models Pantothenate Kinase-Associated Neurodegeneration by Reducing Motor Coordination in Mice.

    Directory of Open Access Journals (Sweden)

    Stephanie A Shumar

    Full Text Available Pantothenate kinase-associated neurodegeneration, PKAN, is an inherited disorder characterized by progressive impairment in motor coordination and caused by mutations in PANK2, a human gene that encodes one of four pantothenate kinase (PanK isoforms. PanK initiates the synthesis of coenzyme A (CoA, an essential cofactor that plays a key role in energy metabolism and lipid synthesis. Most of the mutations in PANK2 reduce or abolish the activity of the enzyme. This evidence has led to the hypothesis that lower CoA might be the underlying cause of the neurodegeneration in PKAN patients; however, no mouse model of the disease is currently available to investigate the connection between neuronal CoA levels and neurodegeneration. Indeed, genetic and/or dietary manipulations aimed at reducing whole-body CoA synthesis have not produced a desirable PKAN model, and this has greatly hindered the discovery of a treatment for the disease.Cellular CoA levels are tightly regulated by a balance between synthesis and degradation. CoA degradation is catalyzed by two peroxisomal nudix hydrolases, Nudt7 and Nudt19. In this study we sought to reduce neuronal CoA in mice through the alternative approach of increasing Nudt7-mediated CoA degradation. This was achieved by combining the use of an adeno-associated virus-based expression system with the synapsin (Syn promoter. We show that mice with neuronal overexpression of a cytosolic version of Nudt7 (scAAV9-Syn-Nudt7cyt exhibit a significant decrease in brain CoA levels in conjunction with a reduction in motor coordination. These results strongly support the existence of a link between CoA levels and neuronal function and show that scAAV9-Syn-Nudt7cyt mice can be used to model PKAN.

  5. (II) COMPLEX COMPOUND

    African Journals Online (AJOL)

    user

    electrochemical sensors, as well as in various chromatographic ... were carried out using Jenway pH meter Model 3320 and a conductivity ... Figure 1: the proposed molecular structure of the copper (II) Schiff base complex. M = Cu (II) or Mn (II).

  6. and copper(II)

    Indian Academy of Sciences (India)

    Unknown

    (II) and copper(II)–zinc(II) complexes. SUBODH KUMAR1, R N PATEL1*, P V KHADIKAR1 and. K B PANDEYA2. 1 Department of Chemistry, APS University, Rewa 486 003, India. 2 CSJM University, Kanpur 208 016, India e-mail: (R N Patel) ...

  7. Isolated Poly(3-Hydroxybutyrate) (PHB) Granules Are Complex Bacterial Organelles Catalyzing Formation of PHB from Acetyl Coenzyme A (CoA) and Degradation of PHB to Acetyl-CoA▿

    OpenAIRE

    Uchino, Keiichi; Saito, Terumi; Gebauer, Birgit; Jendrossek, Dieter

    2007-01-01

    Poly(3-hydroxybutyrate) (PHB) granules isolated in native form (nPHB granules) from Ralstonia eutropha catalyzed formation of PHB from 14C-labeled acetyl coenzyme A (CoA) in the presence of NADPH and concomitantly released CoA, revealing that PHB biosynthetic proteins (acetoacetyl-CoA thiolase, acetoacetyl-CoA reductase, and PHB synthase) are present and active in isolated nPHB granules in vitro. nPHB granules also catalyzed thiolytic cleavage of PHB in the presence of added CoA, resulting in...

  8. Pius II. a utrakvismus

    OpenAIRE

    Šimek, Milan

    2009-01-01

    Milan Šimek Pius II. a utrakvismus Pius II. and utraquism Based on sources work - out, the thesis aims the description and analysis of the attitude alternation of Enea Sylvio Piccolomini - Pius II to the utraquism. The conclusions stress the postulate that Pius II. did not change that attitude, but just did not succed in quelling the utraquist movement. In the sense of political background that finally led to fatal dissention among both leaders, king Jiří of Poděbrady and pope Pius II.

  9. Complexes of cobalt(II), nickel(II), copper(II), zinc(II), cadmium(II) and dioxouranium(II) with thiophene-2-aldehydethiosemicarbazone

    International Nuclear Information System (INIS)

    Singh, Balwan; Misra, Harihar

    1986-01-01

    Metal complexes of thiosemicarbazides have been known for their pharmacological applications. Significant antitubercular, fungicidal and antiviral activities have been reported for thiosemicarbazides and their derivatives. The present study describes the systhesis and characterisation of complexes of Co II , Cu II , Zn II ,Cd II and UO II with thiosemicarbazone obtained by condensing thiophene-2-aldehyde with thiosemicarbazide. 17 refs., 2 tables. (author)

  10. Mangiferin treatment inhibits hepatic expression of acyl-coenzyme A:diacylglycerol acyltransferase-2 in fructose-fed spontaneously hypertensive rats: a link to amelioration of fatty liver

    Energy Technology Data Exchange (ETDEWEB)

    Xing, Xiaomang; Li, Danyang; Chen, Dilong; Zhou, Liang [Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016 China (China); Chonan, Ritsu [Koei Kogyo Co., Ltd., Tokyo, 101-0063 Japan (Japan); Yamahara, Johji [Pharmafood Institute, Kyoto, 602-8136 Japan (Japan); Wang, Jianwei, E-mail: wangjianwei1968@gmail.com [Department of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016 China (China); Li, Yuhao, E-mail: yuhao@sitcm.edu.au [Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, NSW 2000 Australia (Australia)

    2014-10-15

    Mangiferin, a xanthone glucoside, and its associated traditional herbs have been demonstrated to improve abnormalities of lipid metabolism. However, its underlying mechanisms remain largely unclear. This study investigated the anti-steatotic effect of mangiferin in fructose-fed spontaneously hypertensive rat (SHR)s that have a mutation in sterol regulatory element binding protein (SREBP)-1. The results showed that co-administration of mangiferin (15 mg/kg, once daily, by oral gavage) over 7 weeks dramatically diminished fructose-induced increases in hepatic triglyceride content and Oil Red O-stained area in SHRs. However, blood pressure, fructose and chow intakes, white adipose tissue weight and metabolic parameters (plasma concentrations of glucose, insulin, triglyceride, total cholesterol and non-esterified fatty acids) were unaffected by mangiferin treatment. Mechanistically, mangiferin treatment suppressed acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver. In contrast, mangiferin treatment was without effect on hepatic mRNA and/or protein expression of SREBP-1/1c, carbohydrate response element binding protein, liver pyruvate kinase, fatty acid synthase, acetyl-CoA carboxylase-1, stearoyl-CoA desaturase-1, DGAT-1, monoacyglycerol acyltransferase-2, microsomal triglyceride transfer protein, peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase. Collectively, our results suggest that mangiferin treatment ameliorates fatty liver in fructose-fed SHRs by inhibiting hepatic DGAT-2 that catalyzes the final step in triglyceride biosynthesis. The anti-steatotic effect of mangiferin may occur independently of the hepatic signals associated with de novo fatty acid synthesis and oxidation. - Highlights: • We investigated the anti-steatotic effect of mangiferin (MA) in fructose-fed SHR. • MA (15 mg/kg/day for 7 weeks) ameliorated fructose-induced fatty liver in

  11. Targeting Oxidative Stress, Cytokines and Serotonin Interactions Via Indoleamine 2, 3 Dioxygenase by Coenzyme Q10: Role in Suppressing Depressive Like Behavior in Rats.

    Science.gov (United States)

    Abuelezz, Sally A; Hendawy, Nevien; Magdy, Yosra

    2017-06-01

    Depression is a major health problem in which oxidative stress and inflammation are inextricably connected in its pathophysiology. Coenzyme Q10 (CoQ10) is an important anti-oxidant compound with anti-inflammatory and neuro-protective properties. This study was designed to investigate the hypothesis that CoQ10 by its anti-oxidant and anti-inflammatory potentials can alleviate depressive- like behavior by restoring the balance of the tryptophan catabolites kynurenine/serotonin toward the serotonin pathway by down-regulation of hippocampal indoleamine 2,3-dioxygenase 1 (IDO-1). Depressive-like behavior was induced by chronic unpredictable mild stress (CUMS) protocol including food or water deprivation, cage tilting, reversed light cycle etc. Male Wistar rats were randomly divided into five groups; Control, CUMS, CUMS and CoQ10 (50,100 and 200 mg/kg/day i.p. respectively) groups. CoQ10 effects on different behavioral and biochemical tests were analyzed. CoQ10 showed significant antidepressant efficacy, as evidenced by significantly decreased stress induced changes to forced swimming challenge and open field test, as well as attenuating raised corticosterone level and adrenal glands weight. The anti-oxidant effect of CoQ10 was exhibited by its ability to significantly reduce hippocampal elevated malondialdehyde and 4-hydroxynonenal levels and elevate the reduced glutathione and catalase levels. CoQ10 significantly reduced different pro-inflammatory cytokines levels including interleukin (IL)-1β, IL-2, IL-6 and tumor necrosis factor-α. It suppressed hippocampal IDO-1 and subsequent production of kynurenine and enhanced the hippocampal contents of tryptophan and serotonin. Immunohistochemical analysis revealed that CoQ10 was able to attenuate the elevated microglial CD68 and elevate the astrocyte glial fibrillary acidic protein compared to CUMS group. CoQ10 exhibited antidepressant-like effects on rats exposed to CUMS. This could be attributed to its ability to reduce

  12. Effects of metabolic modifiers such as carnitines, coenzyme Q10, and PUFAs against different forms of neurotoxic insults: metabolic inhibitors, MPTP, and methamphetamine.

    Science.gov (United States)

    Virmani, Ashraf; Gaetani, Franco; Binienda, Zbigniew

    2005-08-01

    A number of strategies using the nutritional approach are emerging for the protection of the brain from damage caused by metabolic toxins, age, or disease. Neural dysfunction and metabolic imbalances underlie many diseases, and the inclusion of metabolic modifiers may provide an alternative and early intervention approach that may prevent further damage. Various models have been developed to study the impact of metabolism on brain function. These have also proven useful in expanding our understanding of neurodegeneration processes. For example, the metabolic compromise induced by inhibitors such as 3-nitropropionic acid (3-NPA), rotenone, and 1-methyl-4-phenylpyridinium (MPP+) can cause neurodegeneration in animal models and these models are thought to simulate the processes that may lead to diseases such as Huntington's and Parkinson's diseases. These inhibitors of metabolism are thought to selectively kill neurons by inhibiting various mitochondrial enzymes. However, the eventual cell death is attributed to oxidative stress damage of selectively vulnerable cells, especially highly differentiated neurons. Various studies indicate that the neurotoxicity resulting from these types of metabolic compromise is related to mitochondrial dysfunction and may be ameliorated by metabolic modifiers such as L-carnitine (L-C), creatine, and coenzyme Q10, as well as by antioxidants such as lipoic acid, vitamin E, and resveratrol. Mitochondrial function and cellular metabolism are also affected by the dietary intake of essential polyunsaturated fatty acids (PUFAs), which may regulate membrane composition and influence cellular processes, especially the inflammatory pathways. Cellular metabolic function may also be ameliorated by caloric restriction diets. L-C is a naturally occurring quaternary ammonium compound that is a vital cofactor for the mitochondrial entry and oxidation of fatty acids. Any factors affecting L-C levels may also affect ATP levels. This endogenous compound

  13. FAR5, a fatty acyl-coenzyme A reductase, is involved in primary alcohol biosynthesis of the leaf blade cuticular wax in wheat (Triticum aestivum L.).

    Science.gov (United States)

    Wang, Yong; Wang, Meiling; Sun, Yulin; Wang, Yanting; Li, Tingting; Chai, Guaiqiang; Jiang, Wenhui; Shan, Liwei; Li, Chunlian; Xiao, Enshi; Wang, Zhonghua

    2015-03-01

    A waxy cuticle that serves as a protective barrier against non-stomatal water loss and environmental damage coats the aerial surfaces of land plants. It comprises a cutin polymer matrix and waxes. Cuticular waxes are complex mixtures of very long chain fatty acids (VLCFAs) and their derivatives. Results show that primary alcohols are the major components of bread wheat (Triticum aestivum L.) leaf blade cuticular waxes. Here, the characterization of TaFAR5 from wheat cv Xinong 2718, which is allelic to TAA1b, an anther-specific gene, is reported. Evidence is presented for a new function for TaFAR5 in the biosynthesis of primary alcohols of leaf blade cuticular wax in wheat. Expression of TaFAR5 cDNA in yeast (Saccharomyces cerevisiae) led to production of C22:0 primary alcohol. The transgenic expression of TaFAR5 in tomato (Solanum lycopersicum) cv MicroTom leaves resulted in the accumulation of C26:0, C28:0, and C30:0 primary alcohols. TaFAR5 encodes an alcohol-forming fatty acyl-coenzyme A reductase (FAR). Expression analysis revealed that TaFAR5 was expressed at high levels in the leaf blades, anthers, pistils, and seeds. Fully functional green fluorescent protein-tagged TaFAR5 protein was localized to the endoplasmic reticulum (ER), the site of primary alcohol biosynthesis. SDS-PAGE analysis indicated that the TaFAR5 protein possessed a molecular mass of 58.4kDa, and it was also shown that TaFAR5 transcript levels were regulated in response to drought, cold, and abscisic acid (ABA). Overall, these data suggest that TaFAR5 plays an important role in the synthesis of primary alcohols in wheat leaf blade. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  14. Anaerobic degradation of 2-aminobenzoic acid (anthranilic acid) via benzoyl-coenzyme A (CoA) and cyclohex-1-enecarboxyl-CoA in a denitrifying bacterium.

    Science.gov (United States)

    Lochmeyer, C; Koch, J; Fuchs, G

    1992-06-01

    The enzymes catalyzing the initial reactions in the anaerobic degradation of 2-aminobenzoic acid (anthranilic acid) were studied with a denitrifying Pseudomonas sp. anaerobically grown with 2-aminobenzoate and nitrate as the sole carbon and energy sources. Cells grown on 2-aminobenzoate are simultaneously adapted to growth with benzoate, whereas cells grown on benzoate degrade 2-aminobenzoate several times less efficiently than benzoate. Evidence for a new reductive pathway of aromatic metabolism and for four enzymes catalyzing the initial steps is presented. The organism contains 2-aminobenzoate-coenzyme A ligase (2-aminobenzoate-CoA ligase), which forms 2-aminobenzoyl-CoA. 2-Aminobenzoyl-CoA is then reductively deaminated to benzoyl-CoA by an oxygen-sensitive enzyme, 2-aminobenzoyl-CoA reductase (deaminating), which requires a low potential reductant [Ti(III)]. The specific activity is 15 nmol of 2-aminobenzoyl-CoA reduced min-1 mg-1 of protein at an optimal pH of 7. The two enzymes are induced by the substrate under anaerobic conditions only. Benzoyl-CoA is further converted in vitro by reduction with Ti(III) to six products; the same products are formed when benzoyl-CoA or 2-aminobenzoyl-CoA is incubated under reducing conditions. Two of them were identified preliminarily. One product is cyclohex-1-enecarboxyl-CoA, the other is trans-2-hydroxycyclohexane-carboxyl-CoA. The complex transformation of benzoyl-CoA is ascribed to at least two enzymes, benzoyl-CoA reductase (aromatic ring reducing) and cyclohex-1-enecarboxyl-CoA hydratase. The reduction of benzoyl-CoA to alicyclic compounds is catalyzed by extracts from cells grown anaerobically on either 2-aminobenzoate or benzoate at almost the same rate (10 to 15 nmol min-1 mg-1 of protein). In contrast, extracts from cells grown anaerobically on acetate or grown aerobically on benzoate or 2-aminobenzoate are inactive. This suggests a sequential induction of the enzymes.

  15. Mangiferin treatment inhibits hepatic expression of acyl-coenzyme A:diacylglycerol acyltransferase-2 in fructose-fed spontaneously hypertensive rats: a link to amelioration of fatty liver

    International Nuclear Information System (INIS)

    Xing, Xiaomang; Li, Danyang; Chen, Dilong; Zhou, Liang; Chonan, Ritsu; Yamahara, Johji; Wang, Jianwei; Li, Yuhao

    2014-01-01

    Mangiferin, a xanthone glucoside, and its associated traditional herbs have been demonstrated to improve abnormalities of lipid metabolism. However, its underlying mechanisms remain largely unclear. This study investigated the anti-steatotic effect of mangiferin in fructose-fed spontaneously hypertensive rat (SHR)s that have a mutation in sterol regulatory element binding protein (SREBP)-1. The results showed that co-administration of mangiferin (15 mg/kg, once daily, by oral gavage) over 7 weeks dramatically diminished fructose-induced increases in hepatic triglyceride content and Oil Red O-stained area in SHRs. However, blood pressure, fructose and chow intakes, white adipose tissue weight and metabolic parameters (plasma concentrations of glucose, insulin, triglyceride, total cholesterol and non-esterified fatty acids) were unaffected by mangiferin treatment. Mechanistically, mangiferin treatment suppressed acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver. In contrast, mangiferin treatment was without effect on hepatic mRNA and/or protein expression of SREBP-1/1c, carbohydrate response element binding protein, liver pyruvate kinase, fatty acid synthase, acetyl-CoA carboxylase-1, stearoyl-CoA desaturase-1, DGAT-1, monoacyglycerol acyltransferase-2, microsomal triglyceride transfer protein, peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase. Collectively, our results suggest that mangiferin treatment ameliorates fatty liver in fructose-fed SHRs by inhibiting hepatic DGAT-2 that catalyzes the final step in triglyceride biosynthesis. The anti-steatotic effect of mangiferin may occur independently of the hepatic signals associated with de novo fatty acid synthesis and oxidation. - Highlights: • We investigated the anti-steatotic effect of mangiferin (MA) in fructose-fed SHR. • MA (15 mg/kg/day for 7 weeks) ameliorated fructose-induced fatty liver in

  16. Coenzyme Q10 quantification in muscle, fibroblasts and cerebrospinal fluid by liquid chromatography/tandem mass spectrometry using a novel deuterated internal standard.

    Science.gov (United States)

    Duberley, Kate E C; Hargreaves, Iain P; Chaiwatanasirikul, Korn-Anong; Heales, Simon J R; Land, John M; Rahman, Shamima; Mills, Kevin; Eaton, Simon

    2013-05-15

    Neurological dysfunction is common in primary coenzyme Q10 (2,3-dimethoxy, 5-methyl, 6-polyisoprene parabenzoquinone; CoQ10 ; ubiquinone) deficiencies, the most readily treatable subgroup of mitochondrial disorders. Therapeutic benefit from CoQ10 supplementation has also been noted in other neurodegenerative diseases. CoQ10 can be measured by high-performance liquid chromatography (HPLC) in plasma, muscle or leucocytes; however, there is no reliable method to quantify CoQ10 in cerebrospinal fluid (CSF). Additionally, many methods use CoQ9 , an endogenous ubiquinone in humans, as an internal standard. Deuterated CoQ10 (d6 -CoQ10 ) was synthesised by a novel, simple, method. Total CoQ10 was measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS) using d6 -CoQ10 as internal standard and 5 mM methylamine as an ion-pairing reagent. Chromatography was performed using a Hypsersil GOLD C4 column (150 × 3 mm, 3 µm). CoQ10 levels were linear over a concentration range of 0-200 nM (R(2) = 0.9995). The lower limit of detection was 2 nM. The inter-assay coefficient of variation (CV) was 3.6% (10 nM) and 4.3% (20 nM), and intra-assay CV 3.4% (10 nM) and 3.6% (20 nM). Reference ranges were established for CoQ10 in CSF (5.7-8.7 nM; n = 17), fibroblasts (57.0-121.6 pmol/mg; n = 50) and muscle (187.3-430.1 pmol/mg; n = 15). Use of d6 -CoQ10 internal standard has enabled the development of a sensitive LC/MS/MS method to accurately determine total CoQ10 levels. Clinical applications of CSF CoQ10 determination include identification of patients with cerebral CoQ10 deficiency, and monitoring CSF CoQ10 levels following supplementation. Copyright © 2013 John Wiley & Sons, Ltd.

  17. Concerted elevation of acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) activity through independent stimulation of mRNA expression of DGAT1 and DGAT2 by carbohydrate and insulin.

    Science.gov (United States)

    Meegalla, Rupalie L; Billheimer, Jeffrey T; Cheng, Dong

    2002-11-01

    Glucose and insulin are anabolic signals which upregulate the transcriptions of a series of lipogenic enzymes to convert excess carbohydrate into triglycerides for efficient energy storage. These enzymes include ATP-citrate lyase (ACL), acetyl-coenzyme A carboxylase (ACC), fatty acid synthase (FAS), and glycerol-3-phosphate acyltransferase (G3PA). Acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) is important to synthesize fatty acids into triglycerides. Two DGATs from different gene families have recently been identified. In the current study, we report that glucose preferentially enhances DGAT1 mRNA expression, whereas insulin specifically increases the level of DGAT2 mRNA. Treatment of adipocytes with glucose and insulin together results in higher DGAT activity in the membrane than cells treated with either of the agents alone, indicating that glucose and insulin have additive effect on DGAT activation. In mice treated with fast/refeeding protocol, DGAT2 mRNA decreased upon fasting and was replenished upon refeeding in adipose tissue and liver. This pattern of change was not observed for DGAT1. Inasmuch as DGAT1 mRNA is less abundant in liver, we suggest that DGAT1 is more involved in fat absorption in the intestine and in basal level triglyceride synthesis in adipose tissue where it is more highly expressed. In contrast, DGAT2 is more likely to play important roles in assembly of de novo synthesized fatty acids into VLDL particles in the liver.

  18. Quininium tetrachloridozinc(II

    Directory of Open Access Journals (Sweden)

    Li-Zhuang Chen

    2009-10-01

    Full Text Available The asymmetric unit of the title compound {systematic name: 2-[hydroxy(6-methoxyquinolin-1-ium-4-ylmethyl]-8-vinylquinuclidin-1-ium tetrachloridozinc(II}, (C20H26N2O2[ZnCl4], consists of a double protonated quininium cation and a tetrachloridozinc(II anion. The ZnII ion is in a slightly distorted tetrahedral coordination environment. The crystal structure is stabilized by intermolecular N—H...Cl and O—H...Cl hydrogen bonds.

  19. Burkina Faso - BRIGHT II

    Data.gov (United States)

    Millennium Challenge Corporation — Millennium Challenge Corporation hired Mathematica Policy Research to conduct an independent evaluation of the BRIGHT II program. The three main research questions...

  20. cobalt(II), nickel(II)

    Indian Academy of Sciences (India)

    Unknown

    procedures. The supporting electrolyte, NaClO4 used in the voltammetric experiment was purchased from. Sigma. IR spectra were recorded in KBr medium on .... (13⋅6). L = Schiff base ligand form of one broad band envelope. The electronic spectra of Co(II) complex showed two spin-allowed transitions at 17856 and ...

  1. Nuclear physics II

    International Nuclear Information System (INIS)

    Elze, T.

    1988-01-01

    This script consisting of two parts contains the matter of the courses Nuclear Pyhsics I and II, as they were presented in the winter term 1987/88 and summer term 1988 for students of physics at Frankfurt University. In the present part II the matter of the summer term is summarized. (orig.) [de

  2. World War II Homefront.

    Science.gov (United States)

    Garcia, Rachel

    2002-01-01

    Presents an annotated bibliography that provides Web sites focusing on the U.S. homefront during World War II. Covers various topics such as the homefront, Japanese Americans, women during World War II, posters, and African Americans. Includes lesson plan sources and a list of additional resources. (CMK)

  3. Biologically active new Fe(II, Co(II, Ni(II, Cu(II, Zn(II and Cd(II complexes of N-(2-thienylmethylenemethanamine

    Directory of Open Access Journals (Sweden)

    C. SPÎNU

    2008-04-01

    Full Text Available Iron(II, cobalt(II, nickel (II, copper (II, zinc(II and cadmium(II complexes of the type ML2Cl2, where M is a metal and L is the Schiff base N-(2-thienylmethylenemethanamine (TNAM formed by the condensation of 2-thiophenecarboxaldehyde and methylamine, were prepared and characterized by elemental analysis as well as magnetic and spectroscopic measurements. The elemental analyses suggest the stoichiometry to be 1:2 (metal:ligand. Magnetic susceptibility data coupled with electronic, ESR and Mössbauer spectra suggest a distorted octahedral structure for the Fe(II, Co(II and Ni(II complexes, a square-planar geometry for the Cu(II compound and a tetrahedral geometry for the Zn(II and Cd(II complexes. The infrared and NMR spectra of the complexes agree with co-ordination to the central metal atom through nitrogen and sulphur atoms. Conductance measurements suggest the non-electrolytic nature of the complexes, except for the Cu(II, Zn(II and Cd(II complexes, which are 1:2 electrolytes. The Schiff base and its metal chelates were screened for their biological activity against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa and the metal chelates were found to possess better antibacterial activity than that of the uncomplexed Schiff base.

  4. Obesity-induced oocyte mitochondrial defects are partially prevented and rescued by supplementation with co-enzyme Q10 in a mouse model

    Science.gov (United States)

    Boots, C.E.; Boudoures, A.; Zhang, W.; Drury, A.; Moley, K.H.

    2016-01-01

    STUDY QUESTION Does supplementation with co-enzyme Q10 (CoQ10) improve the oocyte mitochondrial abnormalities associated with obesity in mice? SUMMARY ANSWER In an obese mouse model, CoQ10 improves the mitochondrial function of oocytes. WHAT IS KNOWN ALREADY Obesity impairs oocyte quality. Oocytes from mice fed a high-fat/high-sugar (HF/HS) diet have abnormalities in mitochondrial distribution and function and in meiotic progression. STUDY DESIGN, SIZE, DURATION Mice were randomly assigned to a normal, chow diet or an isocaloric HF/HS diet for 12 weeks. After 6 weeks on the diet, half of the mice receiving a normal diet and half of the mice receiving a HF/HS diet were randomly assigned to receive CoQ10 supplementation injections for the remaining 6 weeks. PARTICIPANTS/MATERIALS, SETTING, METHODS Dietary intervention was initiated on C57Bl6 female mice at 4 weeks of age, CoQ10 versus vehicle injections were assigned at 10 weeks, and assays were conducted at 16 weeks of age. Mice were super-ovulated, and oocytes were collected and stained to assess mitochondrial distribution, quantify reactive oxygen species (ROS), assess meiotic spindle formation, and measure metabolites. In vitro fertilization was performed, and blastocyst embryos were transferred into control mice. Oocyte number, fertilization rate, blastulation rate and implantation rate were compared between the four cohorts. Bivariate statistics were performed appropriately. MAIN RESULTS AND THE ROLE OF CHANCE HF/HS mice weighed significantly more than normal diet mice (29 versus 22 g, P< 0.001). CoQ10 supplementation did not influence weight. Levels of ATP, citrate, and phosphocreatine were lower and ROS levels were higher in HF/HS mice than in controls (P< 0.001). CoQ10 supplementation significantly increased the levels of metabolites and decreased ROS levels in oocytes from normal diet mice but not in oocytes from HF/HS mice. However, CoQ10 completely prevented the mitochondrial distribution abnormalities

  5. Evolved H II regions

    International Nuclear Information System (INIS)

    Churchwell, E.

    1975-01-01

    A probable evolutionary sequence of H II regions based on six distinct types of observed objects is suggested. Two examples which may deviate from this idealized sequence, are discussed. Even though a size-mean density relation of H II regions can be used as a rough indication of whether a nebula is very young or evolved, it is argued that such a relation is not likely to be useful for the quantitative assignment of ages to H II regions. Evolved H II regions appear to fit into one of four structural types: rings, core-halos, smooth structures, and irregular or filamentary structures. Examples of each type are given with their derived physical parameters. The energy balance in these nebulae is considered. The mass of ionized gas in evolved H II regions is in general too large to trace the nebula back to single compact H II regions. Finally, the morphological type of the Galaxy is considered from its H II region content. 2 tables, 2 figs., 29 refs

  6. Preliminary PBFA II design

    International Nuclear Information System (INIS)

    Johnson, D.L.; VanDevender, J.P.; Martin, T.H.

    1980-01-01

    The upgrade of Sandia National Laboratories particle beam fusion accelerator, PBFA I, to PBFA II presents several interesting and challenging pulsed power design problems. PBFA II requires increasing the PBFA I output parameters from 2 MV, 30 TW, 1 MJ to 4 MV, 100 TW, 3.5 MJ with the constraint of using much of the same PBFA I hardware. The increased PBFA II output will be obtained by doubling the number of modules (from 36 to 72), increasing the primary energy storage (from 4 MJ to 15 MJ), lowering the pulse forming line (PFL) output impedance, and adding a voltage doubling network

  7. Increase in insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 after supplementation with selenium and coenzyme Q10. A prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens

    Science.gov (United States)

    Johansson, Peter; Aaseth, Jan; Alexander, Jan; Brismar, Kerstin

    2017-01-01

    Background Insulin-like growth factor-1(IGF-1) has a multitude of effects besides cell growth and metabolism. Reports also indicate anti-inflammatory and antioxidative effects. The concentrations of IGF-1 decrease with age and during inflammation. As selenium and coenzyme Q10 are involved in both the antioxidative defense and the inflammatory response, the present study aimed to examine the effects of supplementation with selenium and coenzyme Q10 on concentrations of IGF-1 and its binding protein IGFBP-1 in a population showing reduced cardiovascular mortality following such supplementation. Methods 215 elderly individuals were included and given the intervention for four years. A clinical examination was performed and blood samples were taken at the start and after 48 months. Evaluations of IGF-1, the age adjusted IGF-1 SD score and IGFBP-1 were performed using group mean values, and repeated measures of variance. Findings After supplementation with selenium and coenzyme Q10, applying group mean evaluations, significantly higher IGF-1 and IGF-1 SD scores could be seen in the active treatment group, whereas a decrease in concentration could be seen of the same biomarkers in the placebo group. Applying the repeated measures of variance evaluations, the same significant increase in concentrations of IGF-1 (F = 68; P>0.0001), IGF-1 SD score (F = 29; PIGF-1 as one of the mechanistic effects of the intervention. Conclusion Supplementation with selenium and coenzyme Q10 over four years resulted in increased levels of IGF-1 and the postprandial IGFBP-1, and an increase in the age-corrected IGF-1 SD score, compared with placebo. The effects could be part of the mechanistic explanation behind the surprisingly positive clinical effects on cardiovascular morbidity and mortality reported earlier. However, as the effects of IGF-1 are complex, more research on the result of intervention with selenium and coenzyme Q10 is needed. PMID:28609475

  8. Mn(II), Zn(II) and VO(II) Schiff

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences; Volume 113; Issue 3. Synthesis and characterisation of Cu(II), Ni(II), Mn(II), Zn(II) and VO(II) Schiff base complexes derived from o-phenylenediamine and acetoacetanilide. N Raman Y Pitchaikani Raja A Kulandaisamy. Inorganic Volume 113 Issue 3 June 2001 pp 183-189 ...

  9. The Belle II Experiment

    CERN Document Server

    Kahn, J

    2017-01-01

    Set to begin data taking at the end of 2018, the Belle II experiment is the next-generation B-factory experiment hosted at KEK in Tsukuba, Japan. The experiment represents the cumulative effort from the collaboration of experimental and detector physics, computing, and software development. Taking everything learned from the previous Belle experiment, which ran from 1998 to 2010, Belle II aims to probe deeper than ever before into the field of heavy quark physics. By achieving an integrated luminosity of 50 ab−1 and accumulating 50 times more data than the previous experiment across its lifetime, along with a rewritten analysis framework, the Belle II experiment will push the high precision frontier of high energy physics. This paper will give an overview of the key components and development activities that make the Belle II experiment possible.

  10. Factor II assay

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003674.htm Factor II assay To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  11. Factor II deficiency

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000549.htm Factor II deficiency To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  12. Ni(II

    African Journals Online (AJOL)

    Preferred Customer

    analytical chemistry, catalysis, electrochemistry, ring-opening metathesis ... Ethanol was dried over anhydrous copper(II) sulfate and distilled over metallic sodium. ... All bacteria were inoculated into Nutrient Broth (Difco) and incubated for 24 h ...

  13. NNDSS - Table II. Vibriosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Vibriosis - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding year), and selected...

  14. Disruption Rose Tinted II

    OpenAIRE

    Livingstone, Andrew

    2009-01-01

    'Disruption - Rose Tinted II' continues to engage narratives of historical English china as previously explored in the work 'Rose Tinted'. This work engages the sleepy rural idyll which is overlaid with visual contemporary social commentary.

  15. NNDSS - Table II. Vibriosis

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Vibriosis - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the preceding year), and selected...

  16. Gamble II Facility

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Gamble II produces a high-voltage (2 MV), high-current (1 MA), short (100 ns) pulse of energy of either positive or negative polarity. This terawatt power...

  17. Leo II PC

    Data.gov (United States)

    Kansas Data Access and Support Center — LEO II is a second-generation software system developed for use on the PC, which is designed to convert location references accurately between legal descriptions and...

  18. Tokapole II device

    International Nuclear Information System (INIS)

    Sprott, J.G.

    1978-05-01

    A discussion is given of the design and operation of the Tokapole II device. The following topics are considered: physics considerations, vacuum vessel, poloidal field, ring and support design, toroidal field, vacuum system, initial results, and future plans

  19. copper(II)

    Indian Academy of Sciences (India)

    Unknown

    bis(2,2,6,6-tetramethyl-3,5-heptadionato)copper(II) ... Abstract. Equilibrium concentrations of various condensed and gaseous phases have been thermodyna- ... phere, over a wide range of substrate temperatures and total reactor pressures.

  20. Digital optical computer II

    Science.gov (United States)

    Guilfoyle, Peter S.; Stone, Richard V.

    1991-12-01

    OptiComp is currently completing a 32-bit, fully programmable digital optical computer (DOC II) that is designed to operate in a UNIX environment running RISC microcode. OptiComp's DOC II architecture is focused toward parallel microcode implementation where data is input in a dual rail format. By exploiting the physical principals inherent to optics (speed and low power consumption), an architectural balance of optical interconnects and software code efficiency can be achieved including high fan-in and fan-out. OptiComp's DOC II program is jointly sponsored by the Office of Naval Research (ONR), the Strategic Defense Initiative Office (SDIO), NASA space station group and Rome Laboratory (USAF). This paper not only describes the motivational basis behind DOC II but also provides an optical overview and architectural summary of the device that allows the emulation of any digital instruction set.

  1. SPEAR II performance

    International Nuclear Information System (INIS)

    Paterson, J.M.

    1975-01-01

    The single beam and colliding beam performance of the SLAC electron-positron storage ring SPEAR II is described. The sevenfold increase in harmonic number in SPEAR II in comparison to SPEAR I has made significant changes in single beam behavior. Strong synchrobetatron resonances and a new transverse instability are observed, and our first studies of these phenomena are described. Measurements on current dependent bunch lengthening are presented. (auth)

  2. Computing at Belle II

    International Nuclear Information System (INIS)

    Kuhr, Thomas

    2012-01-01

    Belle II, a next-generation B-factory experiment, will search for new physics effects in a data sample about 50 times larger than the one collected by its predecessor, the Belle experiment. To match the advances in accelerator and detector technology, the computing system and the software have to be upgraded as well. The Belle II computing model is presented and an overview of the distributed computing system and the offline software framework is given.

  3. Nsls-II Boster

    Science.gov (United States)

    Gurov, S. M.; Akimov, A. V.; Akimov, V. E.; Anashin, V. V.; Anchugov, O. V.; Baranov, G. N.; Batrakov, A. M.; Belikov, O. V.; Bekhtenev, E. A.; Blum, E.; Bulatov, A. V.; Burenkov, D. B.; Cheblakov, P. B.; Chernyakin, A. D.; Cheskidov, V. G.; Churkin, I. N.; Davidsavier, M.; Derbenev, A. A.; Erokhin, A. I.; Fliller, R. P.; Fulkerson, M.; Gorchakov, K. M.; Ganetis, G.; Gao, F.; Gurov, D. S.; Hseuh, H.; Hu, Y.; Johanson, M.; Kadyrov, R. A.; Karnaev, S. E.; Karpov, G. V.; Kiselev, V. A.; Kobets, V. V.; Konstantinov, V. M.; Kolmogorov, V. V.; Korepanov, A. A.; Kramer, S.; Krasnov, A. A.; Kremnev, A. A.; Kuper, E. A.; Kuzminykh, V. S.; Levichev, E. B.; Li, Y.; Long, J. De; Makeev, A. V.; Mamkin, V. R.; Medvedko, A. S.; Meshkov, O. I.; Nefedov, N. B.; Neyfeld, V. V.; Okunev, I. N.; Ozaki, S.; Padrazo, D.; Petrov, V. V.; Petrichenkov, M. V.; Philipchenko, A. V.; Polyansky, A. V.; Pureskin, D. N.; Rakhimov, A. R.; Rose, J.; Ruvinskiy, S. I.; Rybitskaya, T. V.; Sazonov, N. V.; Schegolev, L. M.; Semenov, A. M.; Semenov, E. P.; Senkov, D. V.; Serdakov, L. E.; Serednyakov, S. S.; Shaftan, T. V.; Sharma, S.; Shichkov, D. S.; Shiyankov, S. V.; Shvedov, D. A.; Simonov, E. A.; Singh, O.; Sinyatkin, S. V.; Smaluk, V. V.; Sukhanov, A. V.; Tian, Y.; Tsukanova, L. A.; Vakhrushev, R. V.; Vobly, P. D.; Utkin, A. V.; Wang, G.; Wahl, W.; Willeke, F.; Yaminov, K. R.; Yong, H.; Zhuravlev, A.; Zuhoski, P.

    The National Synchrotron Light Source II is a third generation light source, which was constructed at Brookhaven National Laboratory. This project includes a highly-optimized 3 GeV electron storage ring, linac preinjector, and full-energy synchrotron injector. Budker Institute of Nuclear Physics built and delivered the booster for NSLS-II. The commissioning of the booster was successfully completed. This paper reviews fulfilled work by participants.

  4. Therapeutic effects of coenzyme Q10 on dilated cardiomyopathy. Assessment by {sup 123}I-BMIPP myocardial single photon emission computed tomography (SPECT). A multicenter trial in Osaka University Medical School Group

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Tsunehiko; Hori, Masatsugu [Osaka Univ. (Japan). Faculty of Medicine

    1996-01-01

    To evaluate therapeutic effects of Coenzyme Q10 (CoQ10), 15 patients with dilated cardiomyopathy were investigated by {sup 123}I-BMIPP myocardial single photon emission computed tomography (SPECT). The BMIPP defect score was determined semiquantitatively by using representative short and long axial SPECT images. Mean BMIPP defect score with CoQ10 treatment was significantly low, 7.7{+-}6.1 compared to 12.7{+-}7.4 without CoQ10 treatment. On the other hand, in 8 patients of dilated cardiomyopathy, % fractional shortening using echocardiography was not different before and after CoQ10 treatment. In conclusion, {sup 123}I-BMIPP myocardial SPECT was proved to be sensitive to evaluate the therapeutic effects of CoQ10, which improve myocardial mitochondrial function, in the cases of dilated cardiomyopathy. (author).

  5. Gene structure and mutations of glutaryl-coenzyme A dehydrogenase: impaired association of enzyme subunits that is due to an A421V substitution causes glutaric acidemia type I in the Amish.

    Science.gov (United States)

    Biery, B J; Stein, D E; Morton, D H; Goodman, S I

    1996-11-01

    The structure of the human glutaryl coenzyme A dehydrogenase (GCD) gene was determined to contain 11 exons and to span approximately 7 kb. Fibroblast DNA from 64 unrelated glutaric acidemia type I (GA1) patients was screened for mutations by PCR amplification and analysis of SSCP. Fragments with altered electrophoretic mobility were subcloned and sequenced to detect mutations that caused GA1. This report describes the structure of the GCD gene, as well as point mutations and polymorphisms found in 7 of its 11 exons. Several mutations were found in more than one patient, but no one prevalent mutation was detected in the general population. As expected from pedigree analysis, a single mutant allele causes GA1 in the Old Order Amish of Lancaster County, Pennsylvania. Several mutations have been expressed in Escherichia coli, and all produce diminished enzyme activity. Reduced activity in GCD encoded by the A421V mutation in the Amish may be due to impaired association of enzyme subunits.

  6. cAMP response element binding protein1 is essential for activation of steroyl co-enzyme a desaturase 1 (Scd1 in mouse lung type II epithelial cells.

    Directory of Open Access Journals (Sweden)

    Nisha Antony

    Full Text Available Cyclic AMP Response Element-Binding Protein 1 (Creb1 is a transcription factor that mediates cyclic adenosine 3', 5'-monophosphate (cAMP signalling in many tissues. Creb1(-/- mice die at birth due to respiratory failure and previous genome-wide microarray analysis of E17.5 Creb1(-/- fetal mouse lung identified important Creb1-regulated gene targets during lung development. The lipogenic enzymes stearoyl-CoA desaturase 1 (Scd1 and fatty acid synthase (Fasn showed highly reduced gene expression in Creb1(-/- lungs. We therefore hypothesized that Creb1 plays a crucial role in the transcriptional regulation of genes involved in pulmonary lipid biosynthetic pathways during lung development. In this study we confirmed that Scd1 and Fasn mRNA levels were down regulated in the E17.5 Creb1(-/- mouse lung while the lipogenic-associated transcription factors SrebpF1, C/ebpα and Pparγ were increased. In vivo studies using germline (Creb1(-/- and lung epithelial-specific (Creb1(EpiΔ/Δ Creb1 knockout mice showed strongly reduced Scd1, but not Fasn gene expression and protein levels in lung epithelial cells. In vitro studies using mouse MLE-15 epithelial cells showed that forskolin-mediated activation of Creb1 increased both Scd1 gene expression and protein synthesis. Additionally, MLE15 cells transfected with a dominant-negative ACreb vector blocked forskolin-mediated stimulation of Scd1 gene expression. Lipid profiling in MLE15 cells showed that dominant-negative ACreb suppressed forskolin-induced desaturation of ether linked lipids to produce plasmalogens, as well as levels of phosphatidylethanolamine, ceramide and lysophosphatidylcholine. Taken together these results demonstrate that Creb1 is essential for the induction and maintenance of Scd1 in developing fetal mouse lung epithelial cells.

  7. II-VI semiconductor compounds

    CERN Document Server

    1993-01-01

    For condensed matter physicists and electronic engineers, this volume deals with aspects of II-VI semiconductor compounds. Areas covered include devices and applications of II-VI compounds; Co-based II-IV semi-magnetic semiconductors; and electronic structure of strained II-VI superlattices.

  8. About APPLE II Operation

    International Nuclear Information System (INIS)

    Schmidt, T.; Zimoch, D.

    2007-01-01

    The operation of an APPLE II based undulator beamline with all its polarization states (linear horizontal and vertical, circular and elliptical, and continous variation of the linear vector) requires an effective description allowing an automated calculation of gap and shift parameter as function of energy and operation mode. The extension of the linear polarization range from 0 to 180 deg. requires 4 shiftable magnet arrrays, permitting use of the APU (adjustable phase undulator) concept. Studies for a pure fixed gap APPLE II for the SLS revealed surprising symmetries between circular and linear polarization modes allowing for simplified operation. A semi-analytical model covering all types of APPLE II and its implementation will be presented

  9. VATICANO II CONCILIO DOCTRINAL?

    Directory of Open Access Journals (Sweden)

    Horacio Bojorge

    1970-01-01

    Full Text Available It is a century since the army of Victor Manuel invaded Rome and put an end to Vatican I. In this article we try to understand Vatican II linking it to the previous circumtances and binding it to its doctrinal and pastoral character. Vatican II omitted many subjects that seemed important, e. g. not giving any dogmatic definitions. Contrasting with the Tridentine and Vatican I, that were mostly doctrinal, Vatican II was pastoral. But it was also doctrinal as were the two previous also pastoral. The Constitution "Dei Verbum" brings forth the intentions that led John XXIII to summon the Council in 5-8-1962. The world looked confused and agitated. What could the Church do?

  10. Datalogger usando nios ii

    OpenAIRE

    Campoverde Rugel, Luis Enrique; Velásquez Vargas, Washington Adrián; Ponguillo, Ronald

    2013-01-01

    El presente proyecto consiste en la implementación de un Datalogger utilizando el microprocesador NIOS II el cual fue embebido en el FPGA CYCLONE II que se encuentra integrada en la tarjeta de desarrollo ALTERA DE2, el cual obtiene datos de distintos sensores y los almacena en una tarjeta SD Card. Para la realización del proyecto se aplican cuatro etapas. La primera etapa está basada en obtener los datos mediante el uso de sensores y la transmisión usando un PIC, la siguiente etapa se basa...

  11. Results from SAGE II

    International Nuclear Information System (INIS)

    Nico, J.S.

    1994-01-01

    The Russian-American Gallium solar neutrino Experiment (SAGE) began the second phase of operation (SAGE II) in September of 1992. Monthly measurements of the integral flux of solar neutrinos have been made with 55 tonnes of gallium. The K-peak results of the first nine runs of SAGE II give a capture rate of 66 -13 +18 (stat) -7 +5 (sys) SNU. Combined with the SAGE I result of 73 -16 +18 (stat) -7 5 (sys) SNU, the capture rate is 69 -11 +11 (stat) -7 +5 (sys) SNU. This represents only 52%--56% of the capture rate predicted by different Standard Solar Models

  12. Information on Asse II

    International Nuclear Information System (INIS)

    2014-01-01

    The brochure published by BfS describes the actual situation of Asse II with respect to the debate on an interim storage and the status of the realization of a final repository search law. During the visit of the new environment minister Hendricks in the underground facility repository Asse II the issue interim storage site and the retrieval of the corroded casks with radioactive waste were discussed. The challenges for BFS include the acceleration of the retrieval process and the safety of the procedure.

  13. TJ-II project

    International Nuclear Information System (INIS)

    Alejaldre, C.; Gozalo, J.J.A.; Perez, J.B.; Magaria, F.C.; Diaz, J.R.C.; Perez, J.G.; Lopez-Fraguas, A.; Garcia, L.; Krivenski, V.I.; Martin, R.; Navarro, A.P.; Perea, A.; Rodriguez-Yunta, A.; Ayza, M.S.; Varias, A.

    1990-01-01

    The TJ-II device is a medium-size helical-axis stellarator to be built in Madrid. Its main characteristics are potential for high-beta operation; flexibility, i.e., its rotational transform can be varied over a wide range and its shear to some extent; and bean-shaped plasma cross section. The latest understanding of TJ-II physics in the fields of electron cyclotron resonance heating, transport, and magneto-hydrodynamics, and the engineering solutions introduced in its final design are discussed

  14. ECLESIOLOGIA DO VATICANO II

    Directory of Open Access Journals (Sweden)

    Víctor Codina

    2013-01-01

    Full Text Available Não se pode compreender a eclesiologia do Vaticano II sem conhecer a vida, o estilo pastoral e o carisma de João XXIII, que convocou o Concílio e abriu o caminho em direção a uma nova configuração eclesial que acabava com séculos de uma Igreja de Cristandade. O Vaticano II implica uma transição de uma Igreja clerical a uma Igreja Povo de Deus, povo de batizados. A passagem de uma Igreja juridicista e legalista a uma Igreja Mistério de comunhão em Cristo. Mudar de uma Igreja triunfalista e ligada ao poder mundano a uma Igreja vivificada pela força renovadora do Espírito. A Igreja está a caminho rumo ao Reino de Deus juntamente com todos os cristãos e com toda a humanidade. A recepção do Vaticano II supõe uma conversão pastoral: voltar ao Evangelho e abrir-se aos novos sinais dos tempos seguindo o Espírito que inspirou João XXIII. ABSTRACT: You cannot understand the Ecclesiology of Vatican II without knowing the life, the pastoral style and the charisma of John XXIII, who convened the Council and opened the way toward a new ecclesial setting that ended centuries of a church of Christendom. The Vatican II involves a transition from a clerical Church to a “People (baptized people of God” Church. The Vatican II implies the passage from a juridical and legalistic Church to a Church as the Mystery of the communion in Christ. The Vatican II implies the change from a triumphalistic Church and connected to worldly power to a Church vivified by the renewing force of the Spirit. The Church is on its way toward the Kingdom of God together with all Christians and all mankind. The reception of the Vatican II supposes a pastoral conversion: a return to the Gospel and openness to new signs of the times following the Spirit that inspired John XXIII.

  15. Galaxy S II

    CERN Document Server

    Gralla, Preston

    2011-01-01

    Unlock the potential of Samsung's outstanding smartphone with this jargon-free guide from technology guru Preston Gralla. You'll quickly learn how to shoot high-res photos and HD video, keep your schedule, stay in touch, and enjoy your favorite media. Every page is packed with illustrations and valuable advice to help you get the most from the smartest phone in town. The important stuff you need to know: Get dialed in. Learn your way around the Galaxy S II's calling and texting features.Go online. Browse the Web, manage email, and download apps with Galaxy S II's 3G/4G network (or create you

  16. Calculus II For Dummies

    CERN Document Server

    Zegarelli, Mark

    2012-01-01

    An easy-to-understand primer on advanced calculus topics Calculus II is a prerequisite for many popular college majors, including pre-med, engineering, and physics. Calculus II For Dummies offers expert instruction, advice, and tips to help second semester calculus students get a handle on the subject and ace their exams. It covers intermediate calculus topics in plain English, featuring in-depth coverage of integration, including substitution, integration techniques and when to use them, approximate integration, and improper integrals. This hands-on guide also covers sequences and series, wit

  17. Periodontics II: Course Proposal.

    Science.gov (United States)

    Dordick, Bruce

    A proposal is presented for Periodontics II, a course offered at the Community College of Philadelphia to give the dental hygiene/assisting student an understanding of the disease states of the periodontium and their treatment. A standardized course proposal cover form is given, followed by a statement of purpose for the course, a list of major…

  18. Workshop 96. Part II

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-31

    Part II of the seminar proceedings contains contributions in various areas of science and technology, among them materials science in mechanical engineering, materials science in electrical, chemical and civil engineering, and electronics, measuring and communication engineering. In those areas, 6 contributions have been selected for INIS. (P.A.).

  19. Experiment CATETO II

    International Nuclear Information System (INIS)

    Hendriks, J.A.; Freudenreich, W.E.

    1994-03-01

    In the irradiation experiment CATETO II different reduced activation (RA) steels will be irradiated up to 2.5 dpa at a temperature of 300 C. The results of the calculation of the nuclear constants, the reactivity effect, and the activity of the steel samples are presented. (orig.)

  20. Amorphous iron (II) carbonate

    DEFF Research Database (Denmark)

    Sel, Ozlem; Radha, A.V.; Dideriksen, Knud

    2012-01-01

    Abstract The synthesis, characterization and crystallization energetics of amorphous iron (II) carbonate (AFC) are reported. AFC may form as a precursor for siderite (FeCO3). The enthalpy of crystallization (DHcrys) of AFC is similar to that of amorphous magnesium carbonate (AMC) and more...

  1. Workshop 96. Part II

    International Nuclear Information System (INIS)

    1995-12-01

    Part II of the seminar proceedings contains contributions in various areas of science and technology, among them materials science in mechanical engineering, materials science in electrical, chemical and civil engineering, and electronics, measuring and communication engineering. In those areas, 6 contributions have been selected for INIS. (P.A.)

  2. UNISIST II: Special Report.

    Science.gov (United States)

    Hattery, Lowell H., Ed.

    1979-01-01

    The major part of this report of the Intergovernmental Conference on Scientific and Technical Information (UNISIST II), held in Paris May 28-June 1, 1979, focuses on three sets of recommendations which were unanimously approved after combining the recommendations proposed by various groups and blocs: (1) recommendations to the United Nations…

  3. Photosystem II and photoinhibition

    NARCIS (Netherlands)

    Feikema, Willem Onno

    2006-01-01

    Plants harvest light energy and convert it into chemical energy. Light absorption by photosystems I and II (PSI and PSII) results in charge separations in their reaction centers (RCs), initiating a chain of redox reactions with PSI generating the reducing power for CO2 assimilation into sugars, and

  4. European Telecommunications Satellite II (EUTELSAT II)

    Science.gov (United States)

    Laemmel, G.; Brittinger, P.

    1991-01-01

    EUTELSAT II is a regional public telecommunications system for Europe. The services which will be provided are telephone and television. The satellites will be placed at a geostationary orbit within the arcs of 6 degrees east to 19 degrees east or 26 degrees to 36 degrees east. The designed lifetime is 7 years. After separation of the satellites from the launch vehicles, telemetry, telecommand, and ranging will be performed within the S-band frequencies. After positioning of the satellite at its final geostationary orbit, the Ku-band telecommunication equipment will be activated. From this time on, all satellite control operations will be performed in Ku-band. The Deep Space Network (DSN) will support the transfer and drift orbit mission phases. The coverage will consist of the 26-m antennas at Goldstone and Canberra as prime support for the transfer and drift orbits. Maximum support will consist of a 7-day period, plus 14 days of contingency support. Information is given in tabular form for DSN support, frequency assignments, telemetry, command, and tracking support responsibility.

  5. Ni (II) and Cu(II) complexes of

    African Journals Online (AJOL)

    ADOWIE PERE

    ABSTRACT: The objective of this study is to investigate the antimicrobial activity of novel. Schiff base metal complexes. The resistance of micro-organisms to classical antimicrobial compounds poses a challenge to effective management and treatment of some diseases. In line with this, copper (II), nickel (II) and cobalt (II) ...

  6. Levels of sP-selectin and hs-CRP Decrease with Dietary Intervention with Selenium and Coenzyme Q10 Combined: A Secondary Analysis of a Randomized Clinical Trial

    Science.gov (United States)

    Lindahl, Tomas L.; Svensson, Erland

    2015-01-01

    Background/Objectives Inflammation and oxidative stress are central in many disease states. The major anti-oxidative enzymes contain selenium. The selenium intake in Europe is low, and supplementation with selenium and coenzyme Q10, important anti-oxidants, was evaluated in a previous study. The aim of this study was to evaluate response on the inflammatory biomarkers C-reactive protein, and sP-selectin, and their possible impact on cardiovascular mortality. Subjects/Methods 437 elderly individuals were included in the study. Clinical examination, echocardiography, electrocardiography and blood samples were drawn. The intervention time was 48 months, and median follow-up was 5.2 years. The effects on inflammation/atherosclerosis were evaluated through analyses of CRP and sP-selectin. Evaluations of the effect of the intervention was performed using repeated measures of variance. All mortality was registered, and endpoints of mortality were assessed by Kaplan-Meier plots. Results The placebo group showed a CRP level of 4.8 ng/mL at the start, and 5.1 ng/mL at the study end. The active supplementation group showed a CRP level of 4.1 ng/mL at the start, and 2.1 ng/mL at the study end. SP-selectin exhibited a level of 56.6 mg/mL at the start in the placebo group and 72.3 mg/mL at the study end, and in the active group the corresponding figures were 55.9 mg/mL and 58.0 mg/mL. A significantly smaller increase was demonstrated through repeated measurements of the two biomarkers in those on active supplementation. Active supplementation showed an effect on the CRP and sP-selectin levels, irrespective of the biomarker levels. Reduced cardiovascular mortality was demonstrated in both those with high and low levels of CRP and sP-selectin in the active supplementation group. Conclusion CRP and sP-selectin showed significant changes reflecting effects on inflammation and atherosclerosis in those given selenium and coenzyme Q10 combined. A reduced cardiovascular mortality could

  7. Levels of sP-selectin and hs-CRP Decrease with Dietary Intervention with Selenium and Coenzyme Q10 Combined: A Secondary Analysis of a Randomized Clinical Trial.

    Directory of Open Access Journals (Sweden)

    Urban Alehagen

    Full Text Available Inflammation and oxidative stress are central in many disease states. The major anti-oxidative enzymes contain selenium. The selenium intake in Europe is low, and supplementation with selenium and coenzyme Q10, important anti-oxidants, was evaluated in a previous study. The aim of this study was to evaluate response on the inflammatory biomarkers C-reactive protein, and sP-selectin, and their possible impact on cardiovascular mortality.437 elderly individuals were included in the study. Clinical examination, echocardiography, electrocardiography and blood samples were drawn. The intervention time was 48 months, and median follow-up was 5.2 years. The effects on inflammation/atherosclerosis were evaluated through analyses of CRP and sP-selectin. Evaluations of the effect of the intervention was performed using repeated measures of variance. All mortality was registered, and endpoints of mortality were assessed by Kaplan-Meier plots.The placebo group showed a CRP level of 4.8 ng/mL at the start, and 5.1 ng/mL at the study end. The active supplementation group showed a CRP level of 4.1 ng/mL at the start, and 2.1 ng/mL at the study end. SP-selectin exhibited a level of 56.6 mg/mL at the start in the placebo group and 72.3 mg/mL at the study end, and in the active group the corresponding figures were 55.9 mg/mL and 58.0 mg/mL. A significantly smaller increase was demonstrated through repeated measurements of the two biomarkers in those on active supplementation. Active supplementation showed an effect on the CRP and sP-selectin levels, irrespective of the biomarker levels. Reduced cardiovascular mortality was demonstrated in both those with high and low levels of CRP and sP-selectin in the active supplementation group.CRP and sP-selectin showed significant changes reflecting effects on inflammation and atherosclerosis in those given selenium and coenzyme Q10 combined. A reduced cardiovascular mortality could be demonstrated in the active group

  8. Transport phenomena II essentials

    CERN Document Server

    REA, The Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Transport Phenomena II covers forced convention, temperature distribution, free convection, diffusitivity and the mechanism of mass transfer, convective mass transfer, concentration

  9. Information on Asse II

    International Nuclear Information System (INIS)

    2015-01-01

    The information brochure on Asse II describes the situation in the repository for radioactive wastes that was closed by law due to the violations of safety standards. The discussed topics include the necessity of waste retrieval, the problems with public anxiety and public information, the hazard of an uncontrolled water ingress (worst case scenario), the work sites in the cavern, man-machine interactions and the cost of the project.

  10. Information on Asse II

    International Nuclear Information System (INIS)

    2014-01-01

    The information on Asse II include the following topics: The image and what is behind - the barrier building Dammjoch built 1914; Fact finding - underground explorations; concept for a site comparison; Learning from experiences - the final repository projects Asse, Gorleben and Morsleben show what should not be done; At first drilling - thereafter building - progress of the recovery duct; The retrieval can only go on in dialogue with the public.

  11. Heat transfer II essentials

    CERN Document Server

    REA, The Editors of

    1988-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Heat Transfer II reviews correlations for forced convection, free convection, heat exchangers, radiation heat transfer, and boiling and condensation.

  12. Numerical analysis II essentials

    CERN Document Server

    REA, The Editors of; Staff of Research Education Association

    1989-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Numerical Analysis II covers simultaneous linear systems and matrix methods, differential equations, Fourier transformations, partial differential equations, and Monte Carlo methods.

  13. Review on technology II

    International Nuclear Information System (INIS)

    Mroziewicz, B.

    1986-01-01

    The most important requirements for the spectral properties of photodetectors are reviewed with particular attention to the fiber optics applications. Data on a number of materials are collected and presented. Pros and cons are pointed out for each type of photodetector-photoconductor, p-i-n photodiode and APD. A review is given of the relevant papers presented in the poster session 'Technology II' of the Symposium

  14. Algebra & trigonometry II essentials

    CERN Document Server

    REA, Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Algebra & Trigonometry II includes logarithms, sequences and series, permutations, combinations and probability, vectors, matrices, determinants and systems of equations, mathematica

  15. EASI graphics - Version II

    International Nuclear Information System (INIS)

    Allensworth, J.A.

    1984-04-01

    EASI (Estimate of Adversary Sequence Interruption) is an analytical technique for measuring the effectiveness of physical protection systems. EASI Graphics is a computer graphics extension of EASI which provides a capability for performing sensitivity and trade-off analyses of the parameters of a physical protection system. This document reports on the implementation of the Version II of EASI Graphics and illustrates its application with some examples. 5 references, 15 figures, 6 tables

  16. BeII** revisited

    International Nuclear Information System (INIS)

    Fischer, C.F.

    1982-01-01

    Doubly excited 1s2snl and 1s2pnl quartet states of BeII** are readily populated in beam-foil experiments and line-rich spectra have been obtained covering 600 to 5500 A wavelength range. In spite of several theoretical calculations a substantial number of observed lines have not been identified. The quartet system in BeII is an intersting one from a theoretical point of view. Three electron systems are simple enough that a fairly high level of accuracy is attainable without the calculations becoming horrendous. The important correlation effects are between the outer two electrons and, to a good approximation, the three-electrons system may be treated as a two-electron system outside a 1s-core. The multi-configuration Hartree-Fock (MCHF) method has been used successfully in a number of studies. Programs are under development that take into account the non-orthogonality of orbitals in the initial and final state, and allow for some non-orthogonal orbitals in a wavefunction expansion. LS dependent relativistic effects are also included. A study of BeII** was undertaken to evaluate the MCHF techniques being developed and to assit in the identification of observed lines. Most of the earlier calculations concentrated on the lower-lying levels. In this work particular attention was given to the more highly-excited states, though calculations for lower-lying states had to be repeated in order to predict life-times

  17. What is LAMPF II

    International Nuclear Information System (INIS)

    Thiessen, H.A.

    1982-08-01

    The present conception of LAMPF II is a high-intensity 16-GeV synchrotron injected by the LAMPF 800-MeV H - beam. The proton beam will be used to make secondary beams of neutrinos, muons, pions, kaons, antiprotons, and hyperons more intense than those of any existing or proposed accelerator. For example, by taking maximum advantage of a thick target, modern beam optics, and the LAMPF II proton beam, it will be possible to make a negative muon beam with nearly 100% duty factor and nearly 100 times the flux of the existing Stopped Muon Channel (SMC). Because the unique features of the proposed machine are most applicable to beams of the same momentum as LAMPF (that is, < 2 GeV/c), it may be possible to use most of the experimental areas and some of the auxiliary equipment, including spectrometers, with the new accelerator. The complete facility will provide improved technology for many areas of physics already available at LAMPF and will allow expansion of medium-energy physics to include kaons, antiprotons, and hyperons. When LAMPF II comes on line in 1990 LAMPF will have been operational for 18 years and a major upgrade such as this proposal will be reasonable and prudent

  18. What is LAMPF II

    Energy Technology Data Exchange (ETDEWEB)

    Thiessen, H.A.

    1982-08-01

    The present conception of LAMPF II is a high-intensity 16-GeV synchrotron injected by the LAMPF 800-MeV H/sup -/ beam. The proton beam will be used to make secondary beams of neutrinos, muons, pions, kaons, antiprotons, and hyperons more intense than those of any existing or proposed accelerator. For example, by taking maximum advantage of a thick target, modern beam optics, and the LAMPF II proton beam, it will be possible to make a negative muon beam with nearly 100% duty factor and nearly 100 times the flux of the existing Stopped Muon Channel (SMC). Because the unique features of the proposed machine are most applicable to beams of the same momentum as LAMPF (that is, < 2 GeV/c), it may be possible to use most of the experimental areas and some of the auxiliary equipment, including spectrometers, with the new accelerator. The complete facility will provide improved technology for many areas of physics already available at LAMPF and will allow expansion of medium-energy physics to include kaons, antiprotons, and hyperons. When LAMPF II comes on line in 1990 LAMPF will have been operational for 18 years and a major upgrade such as this proposal will be reasonable and prudent.

  19. Angiotensin II reduces cardiac AdipoR1 expression through AT1 receptor/ROS/ERK1/2/c-Myc pathway.

    Directory of Open Access Journals (Sweden)

    Li Li

    Full Text Available Adiponectin, an abundant adipose tissue-derived protein, exerts protective effect against cardiovascular disease. Adiponectin receptors (AdipoR1 and AdipoR2 mediate the beneficial effects of adiponectin on the cardiovascular system. However, the alteration of AdipoRs in cardiac remodeling is not fully elucidated. Here, we investigated the effect of angiotensin II (AngII on cardiac AdipoRs expression and explored the possible molecular mechanism. AngII infusion into rats induced cardiac hypertrophy, reduced AdipoR1 but not AdipoR2 expression, and attenuated the phosphorylations of adenosine monophosphate-activated protein kinase and acetyl coenzyme A carboxylase, and those effects were all reversed by losartan, an AngII type 1 (AT1 receptor blocker. AngII reduced expression of AdipoR1 mRNA and protein in cultured neonatal rat cardiomyocytes, which was abolished by losartan, but not by PD123319, an AT2 receptor antagonist. The antioxidants including reactive oxygen species (ROS scavenger NAC, NADPH oxidase inhibitor apocynin, Nox2 inhibitor peptide gp91 ds-tat, and mitochondrial electron transport chain complex I inhibitor rotenone attenuated AngII-induced production of ROS and phosphorylation of extracellular signal-regulated kinase (ERK 1/2. AngII-reduced AdipoR1 expression was reversed by pretreatment with NAC, apocynin, gp91 ds-tat, rotenone, and an ERK1/2 inhibitor PD98059. Chromatin immunoprecipitation assay demonstrated that AngII provoked the recruitment of c-Myc onto the promoter region of AdipoR1, which was attenuated by PD98059. Moreover, AngII-induced DNA binding activity of c-Myc was inhibited by losartan, NAC, apocynin, gp91 ds-tat, rotenone, and PD98059. c-Myc small interfering RNA abolished the inhibitory effect of AngII on AdipoR1 expression. Our results suggest that AngII inhibits cardiac AdipoR1 expression in vivo and in vitro and AT1 receptor/ROS/ERK1/2/c-Myc pathway is required for the downregulation of AdipoR1 induced by AngII.

  20. Average [O II] nebular emission associated with Mg II absorbers: dependence on Fe II absorption

    Science.gov (United States)

    Joshi, Ravi; Srianand, Raghunathan; Petitjean, Patrick; Noterdaeme, Pasquier

    2018-05-01

    We investigate the effect of Fe II equivalent width (W2600) and fibre size on the average luminosity of [O II] λλ3727, 3729 nebular emission associated with Mg II absorbers (at 0.55 ≤ z ≤ 1.3) in the composite spectra of quasars obtained with 3 and 2 arcsec fibres in the Sloan Digital Sky Survey. We confirm the presence of strong correlations between [O II] luminosity (L_{[O II]}) and equivalent width (W2796) and redshift of Mg II absorbers. However, we show L_{[O II]} and average luminosity surface density suffer from fibre size effects. More importantly, for a given fibre size, the average L_{[O II]} strongly depends on the equivalent width of Fe II absorption lines and found to be higher for Mg II absorbers with R ≡W2600/W2796 ≥ 0.5. In fact, we show the observed strong correlations of L_{[O II]} with W2796 and z of Mg II absorbers are mainly driven by such systems. Direct [O II] detections also confirm the link between L_{[O II]} and R. Therefore, one has to pay attention to the fibre losses and dependence of redshift evolution of Mg II absorbers on W2600 before using them as a luminosity unbiased probe of global star formation rate density. We show that the [O II] nebular emission detected in the stacked spectrum is not dominated by few direct detections (i.e. detections ≥3σ significant level). On an average, the systems with R ≥ 0.5 and W2796 ≥ 2 Å are more reddened, showing colour excess E(B - V) ˜ 0.02, with respect to the systems with R < 0.5 and most likely trace the high H I column density systems.

  1. Efficiency of emulsifier-free emulsions and emulsions containing rapeseed lecithin as delivery systems for vectorization and release of coenzyme Q10: physico-chemical properties and in vitro evaluation.

    Science.gov (United States)

    Kaci, M; Arab-Tehrany, E; Dostert, G; Desjardins, I; Velot, E; Desobry, S

    2016-11-01

    To improve the encapsulation and release of coenzyme Q10 (CoQ10), emulsifier-free-emulsions were developed with a new emulsification process using high-frequency ultrasound (HFU) at 1.7MHz. Nano-emulsions containing CoQ10 were prepared with or without rapeseed lecithin as an emulsifier. The emulsions prepared with HFU were compared with an emulsion of CoQ10 containing emulsifier prepared with the same emulsification technique as well as with emulsions prepared with low-frequency ultrasound coupled with high-pressure homogenization (LFU+HPH). The physico-chemical properties of the emulsions were determined by average droplet size measurement with nano-droplet tracking analysis, droplet surface charge with ζ potential measurement, surface tension and rheological behaviour. Emulsions made by LFU+HPH with an emulsifier showed lower droplet sizes due to cavitation generated by the HFU process. Surface tension results showed that there was no significant difference between emulsions containing lecithin emulsifier regardless of the preparation process or the inclusion of CoQ10. In vitro biocompatibility tests were performed on human mesenchymal stem cells in order to show the cytotoxicity of various formulations and the efficiency of CoQ10-loaded emulsions. In vitro tests proved that the vectors were not toxic. Furthermore, CoQ10 facilitated a high rate of cell proliferation and metabolic activity especially when in an emulsifier-free formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Regulation of low-density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase expression by Zingiber officinale in the liver of high-fat diet-fed rats.

    Science.gov (United States)

    Nammi, Srinivas; Kim, Moon S; Gavande, Navnath S; Li, George Q; Roufogalis, Basil D

    2010-05-01

    Zingiber officinale has been used to control lipid disorders and reported to possess remarkable cholesterol-lowering activity in experimental hyperlipidaemia. In the present study, the effect of a characterized and standardized extract of Zingiber officinale on the hepatic lipid levels as well as on the hepatic mRNA and protein expression of low-density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was investigated in a high-fat diet-fed rat model. Rats were treated with an ethanol extract of Zingiber officinale (400 mg/kg) extract along with a high-fat diet for 6 weeks. The extract of Zingiber officinale significantly decreased hepatic triglyceride and tended to decrease hepatic cholesterol levels when administered over 6 weeks to the rats fed a high-fat diet. We found that in parallel, the extract up-regulated both LDL receptor mRNA and protein level and down-regulated HMG-CoA reductase protein expression in the liver of these rats. The metabolic control of body lipid homeostasis is in part due to enhanced cholesterol biosynthesis and reduced expression of LDL receptor sites following long-term consumption of high-fat diets. The present results show restoration of transcriptional and post-transcriptional changes in low-density lipoprotein and HMG CoA reductase by Zingiber officinale administration with a high-fat diet and provide a rational explanation for the effect of ginger in the treatment of hyperlipidaemia.

  3. The effects of coenzyme Q10 supplementation on cardiometabolic markers in overweight type 2 diabetic patients with stable myocardial infarction: A randomized, double-blind, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Seyyed Mehdi Mirhashemi

    2016-09-01

    Full Text Available BACKGROUND: Limited data are present that have assessed the effects of coenzyme Q10 (CoQ10 intake on cardiometabolic markers in type 2 diabetic patients with coronary heart disease (CHD. This study was done to determine the effects of CoQ10 administration on cardiometabolic markers in overweight diabetic patients with stable myocardial infarction. METHODS: This randomized double-blind placebo-controlled clinical trial was done among 60 diabetic patients with CHD aged 45-75 years old. Subjects were randomly allocated into two groups to receive either 100 mg/day CoQ10 supplements (n = 30 or placebo (n = 30 for 8 weeks. RESULTS: Compared with the placebo, CoQ10 intake led to a significant reduction in serum interleukin 6 (IL-6 (-1.7 ± 1.6 vs. 0.8 ± 1.7 ng/l, P < 0.001 and protein carbonyl (PCO levels (-0.2 ± 0.3 vs. 0.1 ± 0.2 nmol/mg protein, P < 0.001. Supplementation with CoQ10 did not affect serum lipoprotein(a, advanced glycation end-products and thiol concentrations compared with the placebo. CONCLUSION: Overall, this study indicated that CoQ10 intake after 8 weeks among diabetic patients with the stable CHD had beneficial effects on serum IL-6 and PCO levels, but did not alter other cardiometabolic markers.  

  4. Photoaffinity Labeling of Developing Jojoba Seed Microsomal Membranes with a Photoreactive Analog of Acyl-Coenzyme A (Acyl-CoA) (Identification of a Putative Acyl-CoA:Fatty Alcohol Acyltransferase.

    Science.gov (United States)

    Shockey, J. M.; Rajasekharan, R.; Kemp, J. D.

    1995-01-01

    Jojoba (Simmondsia chinensis, Link) is the only plant known that synthesizes liquid wax. The final step in liquid wax biosynthesis is catalyzed by an integral membrane enzyme, fatty acyl-coenzyme A (CoA):fatty alcohol acyltransferase, which transfers an acyl chain from acyl-CoA to a fatty alcohol to form the wax ester. To purify the acyltransferase, we have labeled the enzyme with a radioiodinated, photoreactive analog of acyl-CoA, 12-[N-(4-azidosalicyl)amino] dodecanoyl-CoA (ASD-CoA). This molecule acts as an inhibitor of acyltransferase activity in the dark and as an irreversible inhibitor upon exposure to ultraviolet light. Oleoyl-CoA protects enzymatic activity in a concentration-dependent manner. Photolysis of microsomal membranes with labeled ASD-CoA resulted in strong labeling of two polypeptides of 57 and 52 kD. Increasing concentrations of oleoyl-CoA reduced the labeling of the 57-kD polypeptide dramatically, whereas the labeling of the 52-kD polypeptide was much less responsive to oleoyl-CoA. Also, unlike the other polypeptide, the labeling of the 57-kD polypeptide was enhanced considerably when photolyzed in the presence of dodecanol. These results suggest that a 57-kD polypeptide from jojoba microsomes may be the acyl-CoA:fatty alcohol acyltransferase.

  5. Bioconversion of α-linolenic acid to n-3 LCPUFA and expression of PPAR-alpha, acyl Coenzyme A oxidase 1 and carnitine acyl transferase I are incremented after feeding rats with α-linolenic acid-rich oils.

    Science.gov (United States)

    González-Mañán, Daniel; Tapia, Gladys; Gormaz, Juan Guillermo; D'Espessailles, Amanda; Espinosa, Alejandra; Masson, Lilia; Varela, Patricia; Valenzuela, Alfonso; Valenzuela, Rodrigo

    2012-07-01

    High dietary intake of n-6 fatty acids in relation to n-3 fatty acids may generate health disorders, such as cardiovascular and other chronic diseases. Fish consumption rich in n-3 fatty acids is low in Latin America, it being necessary to seek other alternatives to provide α-linolenic acid (ALA), precursor of n-3 LCPUFA (EPA and DHA). Two innovative oils were assayed, chia (Salvia hispanica) and rosa mosqueta (Rosa rubiginosa). This study evaluated hepatic bioconversion of ALA to EPA and DHA, expression of PPAR-α, acyl-Coenzyme A oxidase 1 (ACOX1) and carnitine acyltransferase I (CAT-I), and accumulation of EPA and DHA in plasma and adipose tissue in Sprague-Dawley rats. Three experimental groups were fed 21 days: sunflower oil (SFO, control); chia oil (CO); rosa mosqueta oil (RMO). Fatty acid composition of total lipids and phospholipids from plasma, hepatic and adipose tissue was assessed by gas-liquid chromatography and TLC. Expression of PPAR-α (RT-PCR) and ACOX1 and CAT-I (Western blot). CO and RMO increased plasma, hepatic and adipose tissue levels of ALA, EPA and DHA and decreased n-6:n-3 ratio compared to SFO (p oil.

  6. Insight into the molecular mechanism of yeast acetyl-coenzyme A carboxylase mutants F510I, N485G, I69E, E477R, and K73R resistant to soraphen A

    Science.gov (United States)

    Gao, Jian; Liang, Li; Chen, Qingqing; Zhang, Ling; Huang, Tonghui

    2018-02-01

    Acetyl-coenzyme A carboxylases (ACCs) is the first committed enzyme of fatty acid synthesis pathway. The inhibition of ACC is thought to be beneficial not only for diseases related to metabolism, such as type-2 diabetes, but also for infectious disease like bacterial infection disease. Soraphen A, a potent allosteric inhibitor of BC domain of yeast ACC, exhibit lower binding affinities to several yeast ACC mutants and the corresponding drug resistance mechanisms are still unknown. We report here a theoretical study of binding of soraphen A to wild type and yeast ACC mutants (including F510I, N485G, I69E, E477R, and K73R) via molecular dynamic simulation and molecular mechanics/generalized Born surface area free energy calculations methods. The calculated binding free energies of soraphen A to yeast ACC mutants are weaker than to wild type, which is highly consistent with the experimental results. The mutant F510I weakens the binding affinity of soraphen A to yeast ACC mainly by decreasing the van der Waals contributions, while the weaker binding affinities of Soraphen A to other yeast ACC mutants including N485G, I69E, E477R, and K73R are largely attributed to the decreased net electrostatic (ΔE ele + ΔG GB) interactions. Our simulation results could provide important insights for the development of more potent ACC inhibitors.

  7. Specific DNA binding of a potential transcriptional regulator, inosine 5'-monophosphate dehydrogenase-related protein VII, to the promoter region of a methyl coenzyme m reductase I-encoding operon retrieved from Methanothermobacter thermautotrophicus strain DeltaH.

    Science.gov (United States)

    Shinzato, Naoya; Enoki, Miho; Sato, Hiroaki; Nakamura, Kohei; Matsui, Toru; Kamagata, Yoichi

    2008-10-01

    Two methyl coenzyme M reductases (MCRs) encoded by the mcr and mrt operons of the hydrogenotrophic methanogen Methanothermobacter thermautotrophicus DeltaH are expressed in response to H(2) availability. In the present study, cis elements and trans-acting factors responsible for the gene expression of MCRs were investigated by using electrophoretic mobility shift assay (EMSA) and affinity particle purification. A survey of their operator regions by EMSA with protein extracts from mrt-expressing cultures restricted them to 46- and 41-bp-long mcr and mrt upstream regions, respectively. Affinity particle purification of DNA-binding proteins conjugated with putative operator regions resulted in the retrieval of a protein attributed to IMP dehydrogenase-related protein VII (IMPDH VII). IMPDH VII is predicted to have a winged helix-turn-helix DNA-binding motif and two cystathionine beta-synthase domains, and it has been suspected to be an energy-sensing module. EMSA with oligonucleotide probes with unusual sequences showed that the binding site of IMPDH VII mostly overlaps the factor B-responsible element-TATA box of the mcr operon. The results presented here suggest that IMPDH VII encoded by MTH126 is a plausible candidate for the transcriptional regulator of the mcr operon in this methanogen.

  8. Algebra II workbook for dummies

    CERN Document Server

    Sterling, Mary Jane

    2014-01-01

    To succeed in Algebra II, start practicing now Algebra II builds on your Algebra I skills to prepare you for trigonometry, calculus, and a of myriad STEM topics. Working through practice problems helps students better ingest and retain lesson content, creating a solid foundation to build on for future success. Algebra II Workbook For Dummies, 2nd Edition helps you learn Algebra II by doing Algebra II. Author and math professor Mary Jane Sterling walks you through the entire course, showing you how to approach and solve the problems you encounter in class. You'll begin by refreshing your Algebr

  9. Synthesis and spectroscopic studies of biologically active tetraazamacrocyclic complexes of Mn(II, Co(II, Ni(II, Pd(II and Pt(II

    Directory of Open Access Journals (Sweden)

    Monika Tyagi

    2014-01-01

    Full Text Available Complexes of Mn(II, Co(II, Ni(II, Pd(II and Pt(II were synthesized with the macrocyclic ligand, i.e., 2,3,9,10-tetraketo-1,4,8,11-tetraazacycoletradecane. The ligand was prepared by the [2 + 2] condensation of diethyloxalate and 1,3-diamino propane and characterized by elemental analysis, mass, IR and 1H NMR spectral studies. All the complexes were characterized by elemental analysis, molar conductance, magnetic susceptibility measurements, IR, electronic and electron paramagnetic resonance spectral studies. The molar conductance measurements of Mn(II, Co(II and Ni(II complexes in DMF correspond to non electrolyte nature, whereas Pd(II and Pt(II complexes are 1:2 electrolyte. On the basis of spectral studies an octahedral geometry has been assigned for Mn(II, Co(II and Ni(II complexes, whereas square planar geometry assigned for Pd(II and Pt(II. In vitro the ligand and its metal complexes were evaluated against plant pathogenic fungi (Fusarium odum, Aspergillus niger and Rhizoctonia bataticola and some compounds found to be more active as commercially available fungicide like Chlorothalonil.

  10. Removal of Ni (II), Co (II) and Pb (II) ions from aqueous media using ...

    African Journals Online (AJOL)

    Removal of Ni (II), Co (II) and Pb (II) ions from aqueous media using Starch ... The results showed that 0.025 % loaded SSMNPs gave the optimal sorption ... constants (Lagergren and Pseudo-2nd-order) for Ni2+ and Co2+ adsorption were ... Langmuir correlation coefficients showed a better fit for the adsorption isotherms.

  11. Electronics II essentials

    CERN Document Server

    REA, The Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Electronics II covers operational amplifiers, feedback and frequency compensation of OP amps, multivibrators, logic gates and families, Boolean algebra, registers, counters, arithmet

  12. Engineering mathematics-II

    CERN Document Server

    Ganesh, A

    2009-01-01

    About the Book: This book Engineering Mathematics-II is designed as a self-contained, comprehensive classroom text for the second semester B.E. Classes of Visveswaraiah Technological University as per the Revised new Syllabus. The topics included are Differential Calculus, Integral Calculus and Vector Integration, Differential Equations and Laplace Transforms. The book is written in a simple way and is accompanied with explanatory figures. All this make the students enjoy the subject while they learn. Inclusion of selected exercises and problems make the book educational in nature. It shou

  13. Thermodynamics II essentials

    CERN Document Server

    REA, The Editors of

    2013-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Thermodynamics II includes review of thermodynamic relations, power and refrigeration cycles, mixtures and solutions, chemical reactions, chemical equilibrium, and flow through nozzl

  14. Physics II for dummies

    CERN Document Server

    Holzner, Steven

    2010-01-01

    A plain-English guide to advanced physics. Does just thinking about the laws of motion make your head spin? Does studying electricity short your circuits? Physics II For Dummies walks you through the essentials and gives you easy-to-understand and digestible guidance on this often intimidating course. Thanks to this book, you don?t have to be Einstein to understand physics. As you learn about mechanical waves and sound, forces and fields, electric potential and electric energy, and much more, you?ll appreciate the For Dummies law: The easier we make it, the faster you'll understand it!

  15. Physical chemistry II essentials

    CERN Document Server

    REA, The Editors of

    1992-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Physical Chemistry II includes reaction mechanisms, theoretical approaches to chemical kinetics, gravitational work, electrical and magnetic work, surface work, kinetic theory, collisional and transport properties of gases, statistical mechanics, matter and waves, quantum mechanics, and rotations and vibrations of atoms and molecules.

  16. Graphics gems II

    CERN Document Server

    Arvo, James

    1991-01-01

    Graphics Gems II is a collection of articles shared by a diverse group of people that reflect ideas and approaches in graphics programming which can benefit other computer graphics programmers.This volume presents techniques for doing well-known graphics operations faster or easier. The book contains chapters devoted to topics on two-dimensional and three-dimensional geometry and algorithms, image processing, frame buffer techniques, and ray tracing techniques. The radiosity approach, matrix techniques, and numerical and programming techniques are likewise discussed.Graphics artists and comput

  17. Thin film processes II

    CERN Document Server

    Kern, Werner

    1991-01-01

    This sequel to the 1978 classic, Thin Film Processes, gives a clear, practical exposition of important thin film deposition and etching processes that have not yet been adequately reviewed. It discusses selected processes in tutorial overviews with implementation guide lines and an introduction to the literature. Though edited to stand alone, when taken together, Thin Film Processes II and its predecessor present a thorough grounding in modern thin film techniques.Key Features* Provides an all-new sequel to the 1978 classic, Thin Film Processes* Introduces new topics, and sever

  18. Statistics II essentials

    CERN Document Server

    Milewski, Emil G

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Statistics II discusses sampling theory, statistical inference, independent and dependent variables, correlation theory, experimental design, count data, chi-square test, and time se

  19. Data structures II essentials

    CERN Document Server

    Smolarski, Dennis C

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Data Structures II includes sets, trees, advanced sorting, elementary graph theory, hashing, memory management and garbage collection, and appendices on recursion vs. iteration, alge

  20. Computer science II essentials

    CERN Document Server

    Raus, Randall

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Computer Science II includes organization of a computer, memory and input/output, coding, data structures, and program development. Also included is an overview of the most commonly

  1. Synthesis and spectral studies of manganese(II), cobalt(II), nickel(II), copper(II), zinc(II), cadmium(II) and mercury(II) complexes of 4-oxo-4H-1-benzopyran-3-carboxaldehyde hydrazone derivatives

    International Nuclear Information System (INIS)

    Nawar, N.; Khattab, M.A.; Bekheit, M.M.; El-Kaddah, A.H.

    1996-01-01

    A few complexes of Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) with 4-oxo-4H-1-benzopyran-3-(carboxaldehyde-4-chlorobenzylhydrazone) (BCBH) and 4-oxo-4H-1-benzopyran-3-(carboxaldehyde-4-methylbenzylhydrazone) (BMBH) have been synthesised and characterized by elemental analysis, molar conductivities, magnetic measurements and infrared (IR) and visible spectral studies. The IR spectra show that BCBH and BMBH behave as bidentate ligands either in the keto or enol form. (author). 24 refs., 2 tabs

  2. Evaluation of the computerized procedures Manual II (COPMA II)

    International Nuclear Information System (INIS)

    Converse, S.A.

    1995-11-01

    The purpose of this study was to evaluate the effects of a computerized procedure system, the Computerized Procedure Manual II (COPMA-II), on the performance and mental workload of licensed reactor operators. To evaluate COPMA-II, eight teams of two operators were trained to operate a scaled pressurized water reactor facility (SPWRF) with traditional paper procedures and with COPMA-II. Following training, each team operated the SPWRF under normal operating conditions with both paper procedures and COPMA-II. The teams then performed one of two accident scenarios with paper procedures, but performed the remaining accident scenario with COPMA-II. Performance measures and subjective estimates of mental workload were recorded for each performance trial. The most important finding of the study was that the operators committed only half as many errors during the accident scenarios with COPMA-II as they committed with paper procedures. However, time to initiate a procedure was fastest for paper procedures for accident scenario trials. For performance under normal operating conditions, there was no difference in time to initiate or to complete a procedure, or in the number of errors committed with paper procedures and with COPMA-II. There were no consistent differences in the mental workload ratings operators recorded for trials with paper procedures and COPMA-II

  3. Effects of dietary coenzyme Q10 supplementation on hepatic mitochondrial function and the activities of respiratory chain-related enzymes in ascitic broiler chickens.

    Science.gov (United States)

    Geng, A L; Guo, Y M

    2005-10-01

    1. One hundred and sixty 1-d-old Arbor Acre male broiler chicks were fed with maize-soybean based diets for 6 weeks in a 2 x 2 factorial experiment. The factors were CoQ10 supplementation (0 or 40 mg/kg) and Escherichia coli lipopolysaccharide (LPS) challenge (LPS or saline). 2. CoQ10 was supplemented from d 1. From d 18, the chickens received three weekly i.p. injections of LPS (1.0 mg/kg BW) or an equivalent amount of sterile saline as control. From d 10 on, all chickens were exposed to low ambient temperature (12 to 15 degrees C) to induce ascites. 3. The blood packed cell volume and ascites heart index of broiler chickens were reduced by dietary CoQ10 supplementation. Mitochondrial State 3 and State 4 respiration, respiratory control ratio and phosphate oxygen ratio were not changed, but H+/site stoichiometry of complex II + III was elevated by dietary CoQ10 supplementation. 4. Cytochrome c oxidase and H+-ATPase activity were increased by CoQ10 supplementation, whereas NADH cytochrome c reductase and succinate cytochrome c reductase were not influenced. Mitochondrial anti-ROS capability was increased and malondialdehyde content was decreased by CoQ10 supplementation. 5. The work suggested that dietary CoQ10 supplementation could reduce broiler chickens' susceptibility to ascites, which might be the result of improving hepatic mitochondrial function, some respiratory chain-related enzymes activities and mitochondrial antioxidative capability.

  4. RTNS-II utilization

    International Nuclear Information System (INIS)

    Doran, D.G.; Panayotou, N.F.; Powell, R.W.

    1979-12-01

    The objective of the several RTNS-II irradation programs is to maximize information gained from the small test volume available in this unique irradiation facility for application in the fusion materials program. While this facility provides the highest 14 MeV neutron flux available, the flux is generally too low and the irradiation volume too small for testing of engineering materials. Emphasis, therefore, is on identifying damage mechanisms of high energy neutrons and correlating them quantitatively with effects produced by fission neutrons. The information gained will be used to evaluate and calibrate damage and correlation models under development. The scope of the program includes in-situ experiments, postirradiation experiments, irradiation temperatures ranging from 4 0 K to 1,000 0 K, and fluences ranging from 3 x 10 16 to about 3 x 10 19 n/cm 2

  5. Belle II Software

    International Nuclear Information System (INIS)

    Kuhr, T; Ritter, M

    2016-01-01

    Belle II is a next generation B factory experiment that will collect 50 times more data than its predecessor, Belle. The higher luminosity at the SuperKEKB accelerator leads to higher background levels and requires a major upgrade of the detector. As a consequence, the simulation, reconstruction, and analysis software must also be upgraded substantially. Most of the software has been redesigned from scratch, taking into account the experience from Belle and other experiments and utilizing new technologies. The large amount of experimental and simulated data requires a high level of reliability and reproducibility, even in parallel environments. Several technologies, tools, and organizational measures are employed to evaluate and monitor the performance of the software during development. (paper)

  6. Inside ISIS II

    CERN Multimedia

    1981-01-01

    ISIS stands for Identification of Secondaries by Ionization Sampling. It was a drift chamber with an active volume of about 40 m3 built by Oxford University as a particle identifier for the European Hybrid Spectrometer (EHS). The photo shows the electrostatic grading structure and the central anode-wire plane, with Roger Giles standing just under it (Annual Report 1981 p. 57, Fig. 4). ISIS-II differed from the prototype ISIS-I only in the depth of the track (4 m instead of 1 m) thus extending the momentum range for particle identification to 50 GeV/c. See Nucl. Instr. and Meth. 224 (1984) 396, and Nucl. Instr. and Meth. 258 (1987) 26.

  7. Water radiological surveillance (II)

    International Nuclear Information System (INIS)

    Pablo San Martin de, M.

    2008-01-01

    This paper summarizes the characteristics of the Environmental Surveillance Radiological Networks (ESRN) currently operating in CEDEX. In the first part, the Spanish Continental Waters ESRN has been presented. This second one describes Spanish Costal Waters ESRN and the High Sensitivity Networks in Continental and Marine Waters. It also presents the Radiological Surveillance of Drinking Waters that CEDEX carries out in waters of public consumption management by the Canal de Isabel II (CYII) and by the Mancomunity of Canals Taibilla (M.C.T.). The legislation applicable in each case is reviewed as well. Due to its extension the article has been divided into two parts. As Spanish Continental Waters ESRN has been reviewed in the first part, the others ESRN are discussed in this second one. (Author) 10 refs

  8. PEP-II Alignment

    CERN Document Server

    Gaydosh, M

    2003-01-01

    The PEP-II Asymmetric B-factory consists of two independent storage rings, one located atop the other in the 2200m-circumference PEP tunnel. The high-energy ring, which stores a 9-GeV electron beam, is an upgrade of the existing PEP collider. It re-utilizes all of the PEP magnets and incorporates a state-of-the-art copper vacuum chamber and a new RF system capable of supporting a one-amp stored beam. The low-energy ring, which stores 3.1-GeV positrons, is new construction. Injection is achieved by extracting electrons and positrons at collision energies from the SLC and transporting them each in a dedicated bypass line. The low-emittance SLC beams will be used for the injection process.

  9. Stage II Seminoma

    International Nuclear Information System (INIS)

    Sagerman, R.H.; Kotlove, D.J.; Regine, W.; Chung, C.T.; King, G.A.; Dalai, P.S.

    1988-01-01

    Between 1966 and 1985, 32 patients with stage II (21 A,11 B) testicular seminoma were treated with postorchiectomy irradiation to the retroperitoneal and ipsilateral iliac nodes; 28 received elective mediastinal-supraclavicular irradiation. The median follow-up was 8 1/2 years; 29 patients were followed up for over 3 years and 24 for over 5 years. Twenty-eight patients remain alive and well and four have die, two of a second primary cancer. Two patients developed recurrent seminoma in the mediastinum; these patients showed a variant lymphangiographic pattern. Both remain well after further irradiation or irradiation plus chemotherapy. A third patient developed nonseminomatous ''recurrence'' in the radiation field and is well after chemotherapy

  10. Phase II Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Schuknecht, Nate [Project Manager; White, David [Principle Investigator; Hoste, Graeme [Research Engineer

    2014-09-11

    The SkyTrough DSP will advance the state-of-the-art in parabolic troughs for utility applications, with a larger aperture, higher operating temperature, and lower cost. The goal of this project was to develop a parabolic trough collector that enables solar electricity generation in the 2020 marketplace for a 216MWe nameplate baseload power plant. This plant requires an LCOE of 9¢/kWhe, given a capacity factor of 75%, a fossil fuel limit of 15%, a fossil fuel cost of $6.75/MMBtu, $25.00/kWht thermal storage cost, and a domestic installation corresponding to Daggett, CA. The result of our optimization was a trough design of larger aperture and operating temperature than has been fielded in large, utility scale parabolic trough applications: 7.6m width x 150m SCA length (1,118m2 aperture), with four 90mm diameter × 4.7m receivers per mirror module and an operating temperature of 500°C. The results from physical modeling in the System Advisory Model indicate that, for a capacity factor of 75%: The LCOE will be 8.87¢/kWhe. SkyFuel examined the design of almost every parabolic trough component from a perspective of load and performance at aperture areas from 500 to 2,900m2. Aperture-dependent design was combined with fixed quotations for similar parts from the commercialized SkyTrough product, and established an installed cost of $130/m2 in 2020. This project was conducted in two phases. Phase I was a preliminary design, culminating in an optimum trough size and further improvement of an advanced polymeric reflective material. This phase was completed in October of 2011. Phase II has been the detailed engineering design and component testing, which culminated in the fabrication and testing of a single mirror module. Phase II is complete, and this document presents a summary of the comprehensive work.

  11. Effect of Cu(II), Cd(II) and Zn(II) on Pb(II) biosorption by algae Gelidium-derived materials.

    Science.gov (United States)

    Vilar, Vítor J P; Botelho, Cidália M S; Boaventura, Rui A R

    2008-06-15

    Biosorption of Pb(II), Cu(II), Cd(II) and Zn(II) from binary metal solutions onto the algae Gelidium sesquipedale, an algal industrial waste and a waste-based composite material was investigated at pH 5.3, in a batch system. Binary Pb(II)/Cu(II), Pb(II)/Cd(II) and Pb(II)/Zn(II) solutions have been tested. For the same equilibrium concentrations of both metal ions (1 mmol l(-1)), approximately 66, 85 and 86% of the total uptake capacity of the biosorbents is taken by lead ions in the systems Pb(II)/Cu(II), Pb(II)/Cd(II) and Pb(II)/Zn(II), respectively. Two-metal results were fitted to a discrete and a continuous model, showing the inhibition of the primary metal biosorption by the co-cation. The model parameters suggest that Cd(II) and Zn(II) have the same decreasing effect on the Pb(II) uptake capacity. The uptake of Pb(II) was highly sensitive to the presence of Cu(II). From the discrete model it was possible to obtain the Langmuir affinity constant for Pb(II) biosorption. The presence of the co-cations decreases the apparent affinity of Pb(II). The experimental results were successfully fitted by the continuous model, at different pH values, for each biosorbent. The following sequence for the equilibrium affinity constants was found: Pb>Cu>Cd approximately Zn.

  12. Aerospace Systems Monitor, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Proposal Title: Aerospace Systems Monitor PHASE 1 Technical Abstract: This Phase II STTR project will continue development and commercialization of the Aerospace...

  13. Lead (II) and nickel (II) adsorption kinetics from aqueous metal ...

    African Journals Online (AJOL)

    This paper discusses the kinetics of lead (II) and Nickel (II) ions adsorption from aqueous solutions using chemically modified and unmodified agricultural adsorbents at 28°C, pH 6.2 and 0.01M NaCl ionic strength. The removal of the two metals were found to increase with increase in chemical modification, the sequence ...

  14. Non-enzymatic N-acetylation of Lysine Residues by AcetylCoA Often Occurs via a Proximal S-acetylated Thiol Intermediate Sensitive to Glyoxalase II

    Directory of Open Access Journals (Sweden)

    Andrew M. James

    2017-02-01

    Full Text Available Summary: Acetyl coenzyme A (AcCoA, a key intermediate in mitochondrial metabolism, N-acetylates lysine residues, disrupting and, in some cases, regulating protein function. The mitochondrial lysine deacetylase Sirtuin 3 (Sirt3 reverses this modification with benefits reported in diabetes, obesity, and aging. We show that non-enzymatic lysine N-acetylation by AcCoA is greatly enhanced by initial acetylation of a cysteine residue, followed by SN-transfer of the acetyl moiety to a nearby lysine on mitochondrial proteins and synthetic peptides. The frequent occurrence of an S-acetyl intermediate before lysine N-acetylation suggests that proximity to a thioester is a key determinant of lysine susceptibility to acetylation. The thioesterase glyoxalase II (Glo2 can limit protein S-acetylation, thereby preventing subsequent lysine N-acetylation. This suggests that the hitherto obscure role of Glo2 in mitochondria is to act upstream of Sirt3 in minimizing protein N-acetylation, thus limiting protein dysfunction when AcCoA accumulates. : James et al. show that the non-enzymatic N-acetylation of lysine residues in mitochondrial proteins frequently occurs via a proximal S-acetylated thiol intermediate. Glutathione equilibrates with this intermediate, allowing the thioesterase glyoxalase II to limit protein lysine N-acetylation. These findings expand our understanding of how protein acetylation arises. Keywords: AcetylCoA, lysine acetylation, glyoxalase

  15. Computation of the free energy change associated with one-electron reduction of coenzyme immersed in water: a novel approach within the framework of the quantum mechanical/molecular mechanical method combined with the theory of energy representation.

    Science.gov (United States)

    Takahashi, Hideaki; Ohno, Hajime; Kishi, Ryohei; Nakano, Masayoshi; Matubayasi, Nobuyuki

    2008-11-28

    The isoalloxazine ring (flavin ring) is a part of the coenzyme flavin adenine dinucleotide and acts as an active site in the oxidation of a substrate. We have computed the free energy change Deltamicro(red) associated with one-electron reduction of the flavin ring immersed in water by utilizing the quantum mechanical/molecular mechanical method combined with the theory of energy representation (QM/MM-ER method) recently developed. As a novel treatment in implementing the QM/MM-ER method, we have identified the excess charge to be attached on the flavin ring as a solute while the remaining molecules, i.e., flavin ring and surrounding water molecules, are treated as solvent species. Then, the reduction free energy can be decomposed into the contribution Deltamicro(red)(QM) due to the oxidant described quantum chemically and the free energy Deltamicro(red)(MM) due to the water molecules represented by a classical model. By the sum of these contributions, the total reduction free energy Deltamicro(red) has been given as -80.1 kcal/mol. To examine the accuracy and efficiency of this approach, we have also conducted the Deltamicro(red) calculation using the conventional scheme that Deltamicro(red) is constructed from the solvation free energies of the flavin rings at the oxidized and reduced states. The conventional scheme has been implemented with the QM/MM-ER method and the calculated Deltamicro(red) has been estimated as -81.0 kcal/mol, showing excellent agreement with the value given by the new approach. The present approach is efficient, in particular, to compute free energy change for the reaction occurring in a protein since it enables ones to circumvent the numerical problem brought about by subtracting the huge solvation free energies of the proteins in two states before and after the reduction.

  16. Low-cost and disposable sensors for the simultaneous determination of coenzyme Q10 and α-lipoic acid using manganese (IV) oxide-modified screen-printed graphene electrodes.

    Science.gov (United States)

    Charoenkitamorn, Kanokwan; Chaiyo, Sudkate; Chailapakul, Orawon; Siangproh, Weena

    2018-04-03

    In this work, for the first time, manganese (IV) oxide-modified screen-printed graphene electrodes (MnO 2 /SPGEs) were developed for the simultaneous electrochemical detection of coenzyme Q10 (CoQ10) and α-lipoic acid (ALA). This sensor exhibits attractive benefits such as simplicity, low production costs, and disposability. Cyclic voltammetry (CV) was used to characterize the electrochemical behavior of the analyte and investigate the capacitance and electroactive surface area of the unmodified and modified electrode surfaces. The electrochemical behavior of CoQ10 and ALA on MnO 2 /SPGEs was also discussed. Additionally, square wave anodic stripping voltammetry (SWASV) was used for the quantitative determination of CoQ10 and ALA. Under optimal conditions, the obtained signals are linear in the concentration range from 2.0 to 75.0 μg mL -1 for CoQ10 and 0.3-25.0 μg mL -1 for ALA. The low limits of detection (LODs) were found to be 0.56 μg mL -1 and 0.088 μg mL -1 for CoQ10 and ALA, respectively. Moreover, we demonstrated the utility and applicability of the MnO 2 /SPGE sensor through simultaneous measurements of CoQ10 and ALA in dietary supplements. The sensor provides high accuracy measurements, exhibiting its high potential for practical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. 3-Sulfinopropionyl-coenzyme A (3SP-CoA) desulfinase from Advenella mimigardefordensis DPN7T: crystal structure and function of a desulfinase with an acyl-CoA dehydrogenase fold

    Science.gov (United States)

    Schürmann, Marc; Meijers, Rob; Schneider, Thomas R.; Steinbüchel, Alexander; Cianci, Michele

    2015-01-01

    3-Sulfinopropionyl-coenzyme A (3SP-CoA) desulfinase (AcdDPN7; EC 3.13.1.4) was identified during investigation of the 3,3′-dithiodipropionic acid (DTDP) catabolic pathway in the betaproteobacterium Advenella mimigardefordensis strain DPN7T. DTDP is an organic disulfide and a precursor for the synthesis of polythioesters (PTEs) in bacteria, and is of interest for biotechnological PTE production. AcdDPN7 catalyzes sulfur abstraction from 3SP-CoA, a key step during the catabolism of DTDP. Here, the crystal structures of apo AcdDPN7 at 1.89 Å resolution and of its complex with the CoA moiety from the substrate analogue succinyl-CoA at 2.30 Å resolution are presented. The apo structure shows that AcdDPN7 belongs to the acyl-CoA dehydrogenase superfamily fold and that it is a tetramer, with each subunit containing one flavin adenine dinucleotide (FAD) molecule. The enzyme does not show any dehydrogenase activity. Dehydrogenase activity would require a catalytic base (Glu or Asp residue) at either position 246 or position 366, where a glutamine and a glycine are instead found, respectively, in this desulfinase. The positioning of CoA in the crystal complex enabled the modelling of a substrate complex containing 3SP-CoA. This indicates that Arg84 is a key residue in the desulfination reaction. An Arg84Lys mutant showed a complete loss of enzymatic activity, suggesting that the guanidinium group of the arginine is essential for desulfination. AcdDPN7 is the first desulfinase with an acyl-CoA dehydrogenase fold to be reported, which underlines the versatility of this enzyme scaffold. PMID:26057676

  18. Coenzyme Q10 instilled as eye drops on the cornea reaches the retina and protects retinal layers from apoptosis in a mouse model of kainate-induced retinal damage.

    Science.gov (United States)

    Lulli, Matteo; Witort, Ewa; Papucci, Laura; Torre, Eugenio; Schipani, Christian; Bergamini, Christian; Dal Monte, Massimo; Capaccioli, Sergio

    2012-12-17

    To evaluate if coenzyme Q10 (CoQ10) can protect retinal ganglion cells (RGCs) from apoptosis and, when instilled as eye drops on the cornea, if it can reach the retina and exert its antiapoptotic activity in this area in a mouse model of kainate (KA)-induced retinal damage. Rat primary or cultured RGCs were subjected to glutamate (50 μM) or chemical hypoxia (Antimycin A, 200 μM) or serum withdrawal (FBS, 0.5%) in the presence or absence of CoQ10 (10 μM). Cell viability was evaluated by light microscopy and fluorescence-activated cell sorting analyses. Apoptosis was evaluated by caspase 3/7 activity and mitochondrion depolarization tetramethylrhodamine ethyl ester analysis. CoQ10 transfer to the retina following its instillation as eye drops on the cornea was quantified by HPLC. Retinal protection by CoQ10 (10 μM) eye drops instilled on the cornea was then evaluated in a mouse model of KA-induced excitotoxic retinal cell apoptosis by cleaved caspase 3 immunohistofluorescence, caspase 3/7 activity assays, and quantification of inhibition of RGC loss. CoQ10 significantly increased viable cells by preventing RGC apoptosis. Furthermore, when topically applied as eye drops to the cornea, it reached the retina, thus substantially increasing local CoQ10 concentration and protecting retinal layers from apoptosis. The ability of CoQ10 eye drops to protect retinal cells from apoptosis in the mouse model of KA-induced retinal damage suggests that topical CoQ10 may be evaluated in designing therapies for treating apoptosis-driven retinopathies.

  19. Solar Type II Radio Bursts and IP Type II Events

    Science.gov (United States)

    Cane, H. V.; Erickson, W. C.

    2005-01-01

    We have examined radio data from the WAVES experiment on the Wind spacecraft in conjunction with ground-based data in order to investigate the relationship between the shocks responsible for metric type II radio bursts and the shocks in front of coronal mass ejections (CMEs). The bow shocks of fast, large CMEs are strong interplanetary (IP) shocks, and the associated radio emissions often consist of single broad bands starting below approx. 4 MHz; such emissions were previously called IP type II events. In contrast, metric type II bursts are usually narrowbanded and display two harmonically related bands. In addition to displaying complete dynamic spectra for a number of events, we also analyze the 135 WAVES 1 - 14 MHz slow-drift time periods in 2001-2003. We find that most of the periods contain multiple phenomena, which we divide into three groups: metric type II extensions, IP type II events, and blobs and bands. About half of the WAVES listings include probable extensions of metric type II radio bursts, but in more than half of these events, there were also other slow-drift features. In the 3 yr study period, there were 31 IP type II events; these were associated with the very fastest CMEs. The most common form of activity in the WAVES events, blobs and bands in the frequency range between 1 and 8 MHz, fall below an envelope consistent with the early signatures of an IP type II event. However, most of this activity lasts only a few tens of minutes, whereas IP type II events last for many hours. In this study we find many examples in the radio data of two shock-like phenomena with different characteristics that occur simultaneously in the metric and decametric/hectometric bands, and no clear example of a metric type II burst that extends continuously down in frequency to become an IP type II event. The simplest interpretation is that metric type II bursts, unlike IP type II events, are not caused by shocks driven in front of CMEs.

  20. Recent results from AMANDA II

    International Nuclear Information System (INIS)

    Hanson, K.; Ahrens, J.; Bai, X.; Barwick, S.W.; Becka, T.; Becker, K.-H.; Bernardini, E.; Bertrand, D.; Binon, F.; Biron, A.; Boeser, S.; Botner, O.; Bouhali, O.; Burgess, T.; Carius, S.; Castermans, T.; Chen, A.; Chirkin, D.; Conrad, J.; Cooley, J.; Cowen, D.F.; Davour, A.; De Clercq, C.; De Young, T.; Desiati, P.; Dewulf, J.-P.; Doksus, P.; Ekstroem, P.; Feser, T.; Gaisser, T.K.; Gaug, M.; Gerhardt, L.; Goldschmidt, A.; Hallgren, A.; Halzen, F.; Hanson, K.; Hardtke, R.; Hauschildt, T.; Hellwig, M.; Herque, P.; Hill, G.C.; Hulth, P.O.; Hundertmark, S.; Jacobsen, J.; Karle, A.; Koci, B.; Koepke, L.; Kuehn, K.; Kowalski, M.; Lamoureux, J.I.; Leich, H.; Leuthold, M.; Lindahl, P.; Liubarsky, I.; Madsen, J.; Marciniewski, P.; Matis, H.S.; McParland, C.P.; Minaeva, Y.; Miocinovic, P.; Morse, R.; Nahnhauer, R.; Neunhoeffer, T.; Niessen, P.; Nygren, D.R.; Ogelman, H.; Olbrechts, Ph.; Perez de los Heros, C.; Pohl, A.C.; Price, P.B.; Przybylski, G.T.; Rawlins, K.; Resconi, E.; Rhode, W.; Ribordy, M.; Richter, S.; Rodriguez Martino, J.; Ross, D.; Sander, H.-G.; Schmidt, T.; Schneider, D.; Schwarz, R.; Silvestri, A.; Solarz, M.; Spiczak, G.M.; Spiering, C.; Steele, D.; Steffen, P.; Stokstad, R.G.; Sudhoff, P.; Sulanke, K.-H.; Taboada, I.; Thollander, L.; Tilav, S.; Walck, C.; Weinheimer, C.; Wiebusch, C.H.; Wiedemann, C.; Wischnewski, R.; Wissing, H.; Woschnagg, K.; Yodh, G.; Young, S.

    2003-01-01

    We present new data taken with the AMANDA-II neutrino telescope array. The AMANDA-II upgrade was completed at the beginning of 2000. It significantly extends the sensitivity of the 10-string AMANDA-B10 detector to high- and ultrahigh-energy neutrino fluxes into regions of interest for probing current astrophysical models which remain unexplored by other experiments

  1. Synthesis, characterization and thermal studies of nickel (II), copper (II), zinc (II) and cadmium (II) complexes with some mixed ligands

    International Nuclear Information System (INIS)

    Mitra, Samiran; Kundu, Parimal; Singh, Rajkumar Bhubon

    1998-01-01

    Dichloro-(DCA) and trichloroacetate(TCA) -cyclic ligand morpholine (Morph)/thiomorpholine (Tmorph)/methylmorpholine (Mmorph)/dimethyl-piperazine (DMP) complexes of nickel (II), copper (II), zinc (II) and cadmium (II) with the compositions [Ni(tmorph) 2 (DCA) 2 ], [Ni(tmorph) 2 (TCA) 2 ].2H 2 O, [Cu(DMP) 2 (TCA) 2 ],[ML 2 X 2 ].nH 2 O where M=Zn II or Cd II , L=Morph, DMP or tmorph and X=DCA or TCA and n=O except in case of [Cd (Morph) 2 (TCA) 2 ] where n=1 have been synthesised. Some intermediate complexes have been isolated by temperature arrest technique (pyrolysis) and characterised. Configurational and conformational changes have been studied by elemental analyses, IR and electronic spectra, magnetic moment data (in the case of Ni(II) and Cu(II) complexes) and thermal analysis. E a * , ΔH, and ΔS for the decomposition reaction of these complexes are evaluated and the stability of the complexes with respect to activation energy has also been compared. The linear correlation has been found between E a * and ΔS for the decomposition of the complexes. (author)

  2. Glossary

    Science.gov (United States)

    ... I : NADH-Coenzyme Q oxidoreductase (part of the Electron Transport Chain). COMPLEX II : Succinate dehydrogenase (part of the Electron Transport Chain). COMPLEX III : Coenzyme Q-cytochrome c oxidoreductase (part ...

  3. Dust in H II regions

    International Nuclear Information System (INIS)

    Isobe, S.

    1977-01-01

    Several pieces of evidence indicate that H II regions may contain dust: 1) the continuum light scattered by dust grains (O'Dell and Hubbard, 1965), 2) thermal radiation from dust grains at infrared wavelengths (Ney and Allen, 1969), 3) the abnormal helium abundance in some H II regions (Peimbert and Costero, 1969), etc. Although observations of the scattered continuum suggest that the H II region cores may be dust-free, dust grains and gas must be well mixed in view of the infrared observations. This difficulty may be solved by introducing globules with sizes approximately 0.001 pc. These globules and the molecular clouds adjacent to H II regions are the main sources supplying dust to H II regions. (Auth.)

  4. RTNS-II operations guidebook

    International Nuclear Information System (INIS)

    Heikkinen, D.W.

    1985-01-01

    This guidebook is intended to provide training criteria, procedures and guidelines for operation of the RTNS-II neutron sources and ancilliary equipment. Use of this document requires full knowledge of the RTNS-II Facility Safety Procedure (FSP) and any Operational Safety Procedures (OSP) in effect. The RTNS-II FSP defines the hazards which may be encountered at RTNS-II and defines the procedures which must be followed in performing any task including operations. The purpose of this document is to provide a central source of detailed information concerning systems and equipment used in operating the RTNS-II neutron sources on a day-to-day basis. All members of the Operations Group are expected to be familiar with its contents. It is also intended to be used in training new members of the Operations Group

  5. BEPC II positron source

    International Nuclear Information System (INIS)

    Pei Guoxi; Sun Yaolin; Liu Jintong; Chi Yunlong; Liu Yucheng; Liu Nianzong

    2006-01-01

    BEPC II-an upgrade project of the Beijing Electron Positron Collider (BEPC) is a factory type of e + e - collider. The fundamental requirements for its injector linac are the beam energy of 1.89 GeV for on-energy injection and a 40 mA positron beam current at the linac end with a low beam emittance of 1.6 μm and a low energy spread of ±0.5% so as to guarantee a higher injection rate (≥50 mA/min) to the storage ring. Since the positron flux is proportional to the primary electron beam power on the target, the authors will increase the electron gun current from 4A to 10A by using a new electron gun system and increase the primary electron energy from 120 MeV to 240 MeV. The positron source itself is an extremely important system for producing more positrons, including a positron converter target chamber, a 12kA flux modulator, the 7m focusing module with DC power supplies and the support. The new positron production linac from the electron gun to the positron source has been installed into the tunnel. In what follows, the authors will emphasize the positron source design, manufacture and tests. (authors)

  6. Dark matter detection - II

    International Nuclear Information System (INIS)

    Zacek, Viktor

    2015-01-01

    The quest for the mysterious missing mass of the universe has become one of the big challenges of today's particle physics and cosmology. Astronomical observations show that only 1% of the matter of the universe is luminous. Moreover there is now convincing evidence that 85% of all gravitationally observable matter in the universe is of a new exotic kind, different from the 'ordinary' matter surrounding us. In a series of three lectures we discuss past, recent and future efforts made world-wide to detect and/or decipher the nature of Dark Matter. In Lecture I we review our present knowledge of the Dark Matter content of the Universe and how experimenters search for it's candidates; In Lecture II we discuss so-called 'direct detection' techniques which allow to search for scattering of galactic dark matter particles with detectors in deep-underground laboratories; we discuss the interpretation of experimental results and the challenges posed by different backgrounds; In Lecture III we take a look at the 'indirect detection' of the annihilation of dark matter candidates in astrophysical objects, such as our sun or the center of the Milky Way; In addition we will have a look at efforts to produce Dark Matter particles directly at accelerators and we shall close with a look at alternative nonparticle searches and future prospects. (author)

  7. Textos sobre Sostenibilidad II

    Directory of Open Access Journals (Sweden)

    Ciudades para un futuro más sostenible http://habitat.aq.upm.es

    2004-12-01

    This issue assembles a selection of articles publicly available on the website Ciudades para un Futuro más Sostenible (CF+S: http://habitat.aq.upm.es. This selection was originally used as a printed companion guide to the public lecture series on ‘‘Sustainability in the Architecture and Urban Project’’, held on March 2004 and organized by the Madrid School of Architecture within the Initiative for a more Sustainable Architecture and Urbanism (IAU+S. The compilation an overall vision on sustainability presents to average audience. The basic criterion to select these articles was therefore a pedagogical one, including those simpler and clearer papers dealing with all main topics in CF+S. However, due to space limitations, many excellent articles available on the website are unfortunately not included within this selection. CF+S was created in 1996 as a partnership between the Spanish Ministry of Works and Madrid School of Architecture. The objective was to translate into Spanish and publish the experiences selected at the International Award for Best Practices in Improving the Living Environment, organized by United Nations after the Istanbul Conference on Human Settlements (Habitat II. CF+S aims to gather documents concerning any kind of actions and experiences both on the territory and the city actually improving people’s living conditions according to the sustainability concept in its strongest sense. It also offers papers, reports and theoretical reflections on the state of and the possible alternatives to urban development nowadays.

  8. Crystal Structure of Rat Carnitine Palmitoyltransferase II (CPT-II)

    Energy Technology Data Exchange (ETDEWEB)

    Hsiao,Y.; Jogl, G.; Esser, V.; Tong, L.

    2006-01-01

    Carnitine palmitoyltransferase II (CPT-II) has a crucial role in the {beta}-oxidation of long-chain fatty acids in mitochondria. We report here the crystal structure of rat CPT-II at 1.9 Angstroms resolution. The overall structure shares strong similarity to those of short- and medium-chain carnitine acyltransferases, although detailed structural differences in the active site region have a significant impact on the substrate selectivity of CPT-II. Three aliphatic chains, possibly from a detergent that is used for the crystallization, were found in the structure. Two of them are located in the carnitine and CoA binding sites, respectively. The third aliphatic chain may mimic the long-chain acyl group in the substrate of CPT-II. The binding site for this aliphatic chain does not exist in the short- and medium-chain carnitine acyltransferases, due to conformational differences among the enzymes. A unique insert in CPT-II is positioned on the surface of the enzyme, with a highly hydrophobic surface. It is likely that this surface patch mediates the association of CPT-II with the inner membrane of the mitochondria.

  9. Options Study - Phase II

    Energy Technology Data Exchange (ETDEWEB)

    R. Wigeland; T. Taiwo; M. Todosow; W. Halsey; J. Gehin

    2010-09-01

    The Options Study has been conducted for the purpose of evaluating the potential of alternative integrated nuclear fuel cycle options to favorably address the issues associated with a continuing or expanding use of nuclear power in the United States. The study produced information that can be used to inform decisions identifying potential directions for research and development on such fuel cycle options. An integrated nuclear fuel cycle option is defined in this study as including all aspects of the entire nuclear fuel cycle, from obtaining natural resources for fuel to the ultimate disposal of used nuclear fuel (UNF) or radioactive wastes. Issues such as nuclear waste management, especially the increasing inventory of used nuclear fuel, the current uncertainty about used fuel disposal, and the risk of nuclear weapons proliferation have contributed to the reluctance to expand the use of nuclear power, even though it is recognized that nuclear power is a safe and reliable method of producing electricity. In this Options Study, current, evolutionary, and revolutionary nuclear energy options were all considered, including the use of uranium and thorium, and both once-through and recycle approaches. Available information has been collected and reviewed in order to evaluate the ability of an option to clearly address the challenges associated with the current implementation and potential expansion of commercial nuclear power in the United States. This Options Study is a comprehensive consideration and review of fuel cycle and technology options, including those for disposal, and is not constrained by any limitations that may be imposed by economics, technical maturity, past policy, or speculated future conditions. This Phase II report is intended to be used in conjunction with the Phase I report, and much information in that report is not repeated here, although some information has been updated to reflect recent developments. The focus in this Options Study was to

  10. National Energy Plan II

    Energy Technology Data Exchange (ETDEWEB)

    None

    1979-01-01

    This volume contains the Administration's second National Energy Plan, as required by section 801 of the Department of Energy Organization Act (Public Law 95-91). A second volume will contain an assessment of the environmental trends associated with the energy futures reported here. Detailed appendices to the Plan will be published separately. The eight chapters and their subtitles are: Crisis and Uncertainty in the World Energy Future (The Immediate Crisis and the Continuing Problem, The Emergence of the Energy Problem, The Uncertainties of the World Energy Future, World Oil Prices, Consequences for the U.S.); The U.S. Energy Future: The Implications for Policy (The Near-, Mid-, and Long-Term, The Strategy in Perspective); Conservation (Historical Changes in Energy Use, Post-Embargo Changes - In Detail, Conservation Policies and Programs, The Role of Conservation); Oil and Gas (Oil, Natural Gas); Coal and Nuclear (Coal, Nuclear, Policy for Coal and Nuclear Power); Solar and Other Inexhaustible Energy Sources (Solar Energy, Geothermal, Fusion, A Strategy for Inexhaustible Resources); Making Decisions Promptly and Fairly (Managing Future Energy Crises: Emergency Planning, Managing the Current Shortfall: The Iranian Response Plan, Managing the Long-Term Energy Problem: The Institutional Framework, Fairness in Energy Policy, Public Participation in the Development of Energy Policy); and NEP-II and the Future (The Second National Energy Plan and the Nation's Energy Future, The Second National Energy Plan and the Economy, Employment and Energy Policy, The Second National Energy Plan and Individuals, The Second National Energy Plan and Capital Markets, and The Second National Energy Plan and the Environment). (ERA citation 04:041097)

  11. Stiffnites. Part II

    Directory of Open Access Journals (Sweden)

    Maria Teresa Pareschi

    2011-06-01

    Full Text Available

    The dynamics of a stiffnite are here inferred. A stiffnite is a sheet-shaped, gravity-driven submarine sediment flow, with a fabric made up of marine ooze. To infer stiffnite dynamics, order of magnitude estimations are used. Field deposits and experiments on materials taken from the literature are also used. Stiffnites can be tens or hundreds of kilometers wide, and a few centimeters/ meters thick. They move on the sea slopes over hundreds of kilometers, reaching submarine velocities as high as 100 m/s. Hard grain friction favors grain fragmentation and formation of triboelectrically electrified particles and triboplasma (i.e., ions + electrons. Marine lipids favor isolation of electrical charges. At first, two basic assumptions are introduced, and checked a posteriori: (a in a flowing stiffnite, magnetic dipole moments develop, with the magnetization proportional to the shear rate. I have named those dipoles as Ambigua. (b Ambigua are ‘vertically frozen’ along stiffnite streamlines. From (a and (b, it follows that: (i Ambigua create a magnetic field (at peak, >1 T. (ii Lorentz forces sort stiffnite particles into two superimposed sheets. The lower sheet, L+, has a sandy granulometry and a net positive electrical charge density. The upper sheet, L–, has a silty muddy granulometry and a net negative electrical charge density; the grains of sheet L– become finer upwards. (iii Faraday forces push ferromagnetic grains towards the base of a stiffnite, so that a peak of magnetic susceptibility characterizes a stiffnite deposit. (iv Stiffnites harden considerably during their motion, due to magnetic confinement. Stiffnite deposits and inferred stiffnite characteristics are compatible with a stable flow behavior against bending, pinch, or other macro instabilities. In the present report, a consistent hypothesis about the nature of Ambigua is provided.

  12. Kursk Operation Simulation and Validation Exercise - Phase II (KOSAVE II)

    National Research Council Canada - National Science Library

    Bauman, Walter

    1998-01-01

    ... (KOSAVE) Study (KOSAVE II) documents, in this report a statistical record of the Kursk battle, as represented in the KDB, for use as both a standalone descriptive record for historians, and as a baseline for a subsequent Phase...

  13. RTNS-II [Rotating Target Neutron Source II] operational summary

    International Nuclear Information System (INIS)

    Heikkinen, D.W.

    1988-09-01

    The Rotating Target Neutron Source II facility (RTNS-II) operated for over nine years. Its purpose was to provide high intensities of 14 MeV neutrons for materials studies in the fusion energy program. For the period from 1982-1987, the facility was supported by both the US (Department of Energy) and Japan (Ministry of Education, Culture, and Science). RTNS-II contains two accelerator-based neutron sources which use the T(d,n) 4 He reaction. In this paper, we will summarize the operational history of RTNS-II. Typical operating parameters are given. In addition, a brief description of the experimental program is presented. The current status and future options for the facility are discussed. 7 refs., 5 tabs

  14. Chemical speciation of Pb(II, Cd(II, Hg(II, Co(II, Ni(II, Cu(II and Zn(II binary complexes of l-methionine in 1,2-propanediol-water mixtures

    Directory of Open Access Journals (Sweden)

    M. Padma Latha

    2007-04-01

    Full Text Available Chemical speciation of Pb(II, Cd(II, Hg(II, Co(II, Ni(II, Cu(II and Zn(II complexes of L-methionine in 0.0-60 % v/v 1,2-propanediol-water mixtures maintaining an ionic strength of 0.16 M at 303 K has been studied pH metrically. The active forms of ligand are LH2+, LH and L-. The predominant species detected are ML, MLH, ML2, ML2H, ML2H2 and MLOH. Models containing different numbers of species were refined by using the computer program MINIQUAD 75. The best-fit chemical models were arrived at based on statistical parameters. The trend in variation of complex stability constants with change in the dielectric constant of the medium is explained on the basis of electrostatic and non-electrostatic forces.

  15. New instruments at IPNS: POSY II and SAD II

    International Nuclear Information System (INIS)

    Crawford, R.K.; Felcher, G.P.; Kleb, R.; Epperson, J.E.; Thiyagarajan, P.

    1988-01-01

    Three new instruments are currently in varying degrees of development/construction at IPNS. One of these, the Glass, Liquid, and Amorphous Materials Diffractometer (GLAD) is the subject of a separate paper in these Proceedings, and so will not be discussed further here. The other two, a second neutron reflectometer (POSY II) and a second small-angle diffractometer (SAD II) are described briefly below. 5 refs., 1 fig., 1 tab

  16. Integrated Procurement Management System, Version II

    Science.gov (United States)

    Collier, L. J.

    1985-01-01

    Integrated Procurement Management System, Version II (IPMS II) is online/ batch system for collecting developing, managing and disseminating procurementrelated data at NASA Johnson Space Center. Portions of IPMS II adaptable to other procurement situations.

  17. Bose Condensate in He II

    International Nuclear Information System (INIS)

    Svensson, E.C.

    1984-01-01

    The Condensate Saga, now halfway through its fifth decade, is reviewed. The recent neutron-scattering work which has at last convincingly established that there is indeed a Bose Condensate in He II is described

  18. Tier II Chemical Storage Facilities

    Data.gov (United States)

    Iowa State University GIS Support and Research Facility — Facilities that store hazardous chemicals above certain quantities must submit an annual emergency and hazardous chemical inventory on a Tier II form. This is a...

  19. Penetrating Internet Information Services (IIS).

    African Journals Online (AJOL)

    PROF. O. E. OSUAGWU

    2013-12-01

    Dec 1, 2013 ... Information Services (IIS) packages have been presented. Note that while some of ... encompasses a variety of services including FTP, SMTP ..... for Web-based Distributed Authoring ... denial-of-service vulnerabilities we have.

  20. Coordination compounds of cobalt(II), nickel(II), copper(II), and zinc(II) with pantothenic acid

    Energy Technology Data Exchange (ETDEWEB)

    Shabilalov, A.A.; Yunuskhodzhaev, A.N.; Khodzhaev, O.F.; Azizov, M.A.

    1986-11-01

    The compounds Ni(PANA - H)/sub 2/ x 4H/sub 2/O (PANA stands for pantothenic acid, and - H indicates a deprotonated ligand), Cu(PANA - H)/sub 2/ x 2H/sub 2/O, Zn(PANA - H)/sub 2/ x H/sub 2/O, Co(PANA - H)Cl x H/sub 2/O, and Ni(PANA - H)Cl x 3H/sub 2/O have been synthesized on the basis of pantothenic acid and Co(II), Ni(II), Cu(II), and Zn(II) salts in aqueous media. The compounds have been identified by elemental and x-ray diffraction analysis. Some physicochemical properties (solubility, melting point, molar conductivity) of the compounds obtained have been studied. The structure of the compounds isolated has been established on the basis of an analysis of their IR, ESR, and electronic spectra, as well as derivatograms.

  1. Lunar Health Monitor, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — During the Phase II Lunar Health Monitor program, Orbital Research will develop a second generation wearable sensor suite for astronaut physiologic monitoring. The...

  2. Australia; Basel II Implementation Assessment

    OpenAIRE

    International Monetary Fund

    2010-01-01

    The key findings of Australia’s BASEL II implementation assessment are presented. The Australian Prudential Regulation Authority (APRA) allocated sufficient resources, including highly skilled staff, prior to the Basel II start date, and the outcome has been a robust and high-quality implementation that has built upon and substantially strengthened the risk-management capabilities of major banks. The quality of leadership and commitment by all involved has been instrumental in the success of ...

  3. Pb(II), Cd(II) and Zn(II) adsorption on low grade manganese ore ...

    African Journals Online (AJOL)

    Low grade manganese ore (LMO) of Orissa containing 58.37% SiO2, 25.05% MnO2, 8.8% Al2O3, and 5.03% Fe2O3 as the main constituents was taken to study its adsorption behaviour for Pb(II), Cd(II) and Zn(II) from aqueous solutions. The XRD studies showed the crystalline phases to be quartz, ß-MnO2, d-MnO2 and ...

  4. Stabilization of the second oxyanion intermediate by 1,4-dihydroxy-2-naphthoyl-coenzyme A synthase of the menaquinone pathway: spectroscopic evidence of the involvement of a conserved aspartic acid.

    Science.gov (United States)

    Chen, Minjiao; Jiang, Ming; Sun, Yueru; Guo, Zu-Feng; Guo, Zhihong

    2011-07-05

    1,4-Dihydroxy-2-naphthoyl-coenzyme A (DHNA-CoA) synthase, or MenB, catalyzes an intramolecular Claisen condensation involving two oxyanion intermediates in the biosynthetic pathway of menaquinone, an essential respiration electron transporter in many microorganisms. Here we report the finding that the DHNA-CoA product and its analogues bind and inhibit the synthase from Escherichia coli with significant ultraviolet--visible spectral changes, which are similar to the changes induced by deprotonation of the free inhibitors in a basic solution. Dissection of the structure--affinity relationships of the inhibitors identifies the hydroxyl groups at positions 1 (C1-OH) and 4 (C4-OH) of DHNA-CoA or their equivalents as the dominant and minor sites, respectively, for the enzyme--ligand interaction that polarizes or deprotonates the bound ligands to cause the observed spectral changes. In the meantime, spectroscopic studies with active site mutants indicate that C4-OH of the enzyme-bound DHNA-CoA interacts with conserved polar residues Arg-91, Tyr-97, and Tyr-258 likely through a hydrogen bonding network that also includes Ser-161. In addition, site-directed mutation of the conserved Asp-163 to alanine causes a complete loss of the ligand binding ability of the protein, suggesting that the Asp-163 side chain is most likely hydrogen-bonded to C1-OH of DHNA-CoA to provide the dominant polarizing effect. Moreover, this mutation also completely eliminates the enzyme activity, strongly supporting the possibility that the Asp-163 side chain provides a strong stabilizing hydrogen bond to the tetrahedral oxyanion, which takes a position similar to that of C1-OH of the enzyme-bound DHNA-CoA and is the second high-energy intermediate in the intracellular Claisen condensation reaction. Interestingly, both Arg-91 and Tyr-97 are located in a disordered loop forming part of the active site of all available DHNA-CoA synthase structures. Their involvement in the interaction with the small

  5. Novel Reaction of Succinyl Coenzyme A (Succinyl-CoA) Synthetase: Activation of 3-Sulfinopropionate to 3-Sulfinopropionyl-CoA in Advenella mimigardefordensis Strain DPN7T during Degradation of 3,3′-Dithiodipropionic Acid ▿ †

    Science.gov (United States)

    Schürmann, Marc; Wübbeler, Jan Hendrik; Grote, Jessica; Steinbüchel, Alexander

    2011-01-01

    The sucCD gene of Advenella mimigardefordensis strain DPN7T encodes a succinyl coenzyme A (succinyl-CoA) synthetase homologue (EC 6.2.1.4 or EC 6.2.1.5) that recognizes, in addition to succinate, the structural analogues 3-sulfinopropionate (3SP) and itaconate as substrates. Accumulation of 3SP during 3,3′-dithiodipropionic acid (DTDP) degradation was observed in Tn5::mob-induced mutants of A. mimigardefordensis strain DPN7T disrupted in sucCD and in the defined deletion mutant A. mimigardefordensis ΔsucCD. These mutants were impaired in growth with DTDP and 3SP as the sole carbon source. Hence, it was proposed that the succinyl-CoA synthetase homologue in A. mimigardefordensis strain DPN7T activates 3SP to the corresponding CoA-thioester (3SP-CoA). The putative genes coding for A. mimigardefordensis succinyl-CoA synthetase (SucCDAm) were cloned and heterologously expressed in Escherichia coli BL21(DE3)/pLysS. Purification and characterization of the enzyme confirmed its involvement during degradation of DTDP. 3SP, the cleavage product of DTDP, was converted into 3SP-CoA by the purified enzyme, as demonstrated by in vitro enzyme assays. The structure of 3SP-CoA was verified by using liquid chromatography-electrospray ionization-mass spectrometry. SucCDAm is Mg2+ or Mn2+ dependent and unspecific regarding ATP or GTP. In kinetic studies the enzyme showed highest enzyme activity and substrate affinity with succinate (Vmax = 9.85 ± 0.14 μmol min−1 mg−1, Km = 0.143 ± 0.001 mM). In comparison to succinate, activity with 3SP was only ca. 1.2% (Vmax = 0.12 ± 0.01 μmol min−1 mg−1) and the affinity was 6-fold lower (Km = 0.818 ± 0.046 mM). Based on the present results, we conclude that SucCDAm is physiologically associated with the citric acid cycle but is mandatory for the catabolic pathway of DTDP and its degradation intermediate 3SP. PMID:21515777

  6. Therapeutic effect of co-enzyme Q10 on idiopathic dilated cardiomyopathy: assessment by iodine-123 labelled 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid myocardial single-photon emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yong-ih [Department of Internal Medicine, Nishiyodo Hospital, Nishiyodo (Japan); Sawada, Yoshihiro [Department of Internal Medicine, Nishiyodo Hospital, Nishiyodo (Japan); Fujiwara, Go [Department of Radiology, Nishiyodo Hospital, Nishiyodo (Japan); Chiba, Hiroshi [Department of Internal Medicine, Mimihara General Hospital, Mimihara (Japan); Nishimura, Tsunehiko [Division of Tracer Kinetics, Biomedical Research Center, Osaka University Medical School, Osaka (Japan)

    1997-06-10

    It has been reported that myocardial mitochondrial function can be improved by the administration of co-enzyme Q10 (CoQ10). Recently, iodine-123 labelled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) was developed for metabolic imaging using single-photon emission tomography (SPET). This study was conducted to determine whether the therapeutic effects of CoQ10 on idiopathic dilated cardiomyopathy can be evaluated by BMIPP myocardial SPET. Fifteen patients, comprising 14 men and one woman (mean age: 64{+-}12 years), were examined. CoQ10 was administered at 30 mg/day for a period of 35.7{+-}12.4 days. BMIPP myocardial SPET was carried out before and after CoQ10 treatment. The count ratio of the heart (H) to the upper mediastinum (M) (H/M ratio) was calculated using a region of interest method with anterior planar imaging. Representative short-axis tomograms were divided into 27 segments (three slices x nine segments). Each segmental score was analysed semiquantitatively using a four-point scoring system (normal=0, mild low uptake=1, severe low uptake=2, defect=3). The H/M ratio showed a significant improvement, from 2.39{+-}0.39 to 2.54{+-}0.47, after treatment (P<0.05). The BMIPP total defect score after CoQ10 treatment was significantly decreased to 10.1{+-}4.3, compared to 13.9{+-}4.5 without CoQ10 treatment (P<0.001). However, the percent fractional shortening measured using echocardiography was not significantly different before and after CoQ treatment (19.2{+-}8.1 vs 19.7{+-}7.1). BMIPP myocardial SPET was confirmed to be sensitive in evaluating the therapeutic effects of CoQ10 in patients with idiopathic dilated cardiomyopathy. This method is unique, since the therapeutic effects can be estimated from the perspective of metabolic SPET imaging. (orig.). With 5 figs., 1 tab.

  7. 6-Oxocyclohex-1-ene-1-carbonyl-coenzyme A hydrolases from obligately anaerobic bacteria: characterization and identification of its gene as a functional marker for aromatic compounds degrading anaerobes.

    Science.gov (United States)

    Kuntze, Kevin; Shinoda, Yoshifumi; Moutakki, Housna; McInerney, Michael J; Vogt, Carsten; Richnow, Hans-Hermann; Boll, Matthias

    2008-06-01

    In anaerobic bacteria, most aromatic growth substrates are channelled into the benzoyl-coenzyme A (CoA) degradation pathway where the aromatic ring is dearomatized and cleaved into an aliphatic thiol ester. The initial step of this pathway is catalysed by dearomatizing benzoyl-CoA reductases yielding the two electron-reduction product, cyclohexa-1,5-diene-1-carbonyl-CoA, to which water is subsequently added by a hydratase. The next two steps have so far only been studied in facultative anaerobes and comprise the oxidation of the 6-hydroxyl-group to 6-oxocyclohex-1-ene-1-carbonyl-CoA (6-OCH-CoA), the addition of water and hydrolytic ring cleavage yielding 3-hydroxypimelyl-CoA. In this work, two benzoate-induced genes from the obligately anaerobic bacteria, Geobacter metallireducens (bamA(Geo)) and Syntrophus aciditrophicus (bamA(Syn)), were heterologously expressed in Escherichia coli, purified and characterized as 6-OCH-CoA hydrolases. Both enzymes consisted of a single 43 kDa subunit. Some properties of the enzymes are presented and compared with homologues from facultative anaerobes. An alignment of the nucleotide sequences of bamA(Geo) and bamA(Syn) with the corresponding genes from facultative anaerobes identified highly conserved DNA regions, which enabled the discrimination of genes coding for 6-OCH-CoA hydrolases from those coding for related enzymes. A degenerate oligonucleotide primer pair was deduced from conserved regions and applied in polymerase chain reaction reactions. Using these primers, the expected DNA fragment of the 6-OCH-CoA hydrolase genes was specifically amplified from the DNA of nearly all known facultative and obligate anaerobes that use aromatic growth substrates. The only exception was the aromatic compound-degrading Rhodopseudomonas palustris, which uniquely uses a modified benzoyl-CoA degradation pathway. Using the oligonucleotide primers, the expected DNA fragment was also amplified in a toluene-degrading and a m

  8. Heterologous Expression of the Clostridium carboxidivorans CO Dehydrogenase Alone or Together with the Acetyl Coenzyme A Synthase Enables both Reduction of CO2 and Oxidation of CO by Clostridium acetobutylicum.

    Science.gov (United States)

    Carlson, Ellinor D; Papoutsakis, Eleftherios T

    2017-08-15

    With recent advances in synthetic biology, CO 2 could be utilized as a carbon feedstock by native or engineered organisms, assuming the availability of electrons. Two key enzymes used in autotrophic CO 2 fixation are the CO dehydrogenase (CODH) and acetyl coenzyme A (acetyl-CoA) synthase (ACS), which form a bifunctional heterotetrameric complex. The CODH/ACS complex can reversibly catalyze CO 2 to CO, effectively enabling a biological water-gas shift reaction at ambient temperatures and pressures. The CODH/ACS complex is part of the Wood-Ljungdahl pathway (WLP) used by acetogens to fix CO 2 , and it has been well characterized in native hosts. So far, only a few recombinant CODH/ACS complexes have been expressed in heterologous hosts, none of which demonstrated in vivo CO 2 reduction. Here, functional expression of the Clostridium carboxidivorans CODH/ACS complex is demonstrated in the solventogen Clostridium acetobutylicum , which was engineered to express CODH alone or together with the ACS. Both strains exhibited CO 2 reduction and CO oxidation activities. The CODH reactions were interrogated using isotopic labeling, thus verifying that CO was a direct product of CO 2 reduction, and vice versa. CODH apparently uses a native C. acetobutylicum ferredoxin as an electron carrier for CO 2 reduction. Heterologous CODH activity depended on actively growing cells and required the addition of nickel, which is inserted into CODH without the need to express the native Ni insertase protein. Increasing CO concentrations in the gas phase inhibited CODH activity and altered the metabolite profile of the CODH-expressing cells. This work provides the foundation for engineering a complete and functional WLP in nonnative host organisms. IMPORTANCE Functional expression of CO dehydrogenase (CODH) from Clostridium carboxidivorans was demonstrated in C. acetobutylicum , which is natively incapable of CO 2 fixation. The expression of CODH, alone or together with the C. carboxidivorans

  9. Cr(III,Mn(II,Fe(III,Co(II,Ni(II,Cu(II and Zn(II Complexes with Diisobutyldithiocarbamato Ligand

    Directory of Open Access Journals (Sweden)

    Mohammad Tarique

    2011-01-01

    Full Text Available The synthesis of sulphur and nitrogen containing dithiocarbamato ligand derived from diisobutylamine as well as its coordination compounds with 3d series transition metals is presented. These synthesized compounds were characterized on the basis of elemental analysis, conductometric measurements and IR spectral studies. The analytical data showed the stoichiometry 1:2 and 1:3 for the compounds of the types ML2 {M=Mn(II, Co(II, Ni(II, Cu(II and Zn(II} and M'L3{M'=Cr(III and Fe(III} respectively. The conductometric measurements proved the non-electrolytic behaviour of all the compounds. The bidentate nature of dithiocarbamato moiety was confirmed on the basis of IR spectral data.

  10. Mu2e-II Injection from PIP-II

    Energy Technology Data Exchange (ETDEWEB)

    Neuffer, David [Fermilab

    2018-04-26

    We discuss injection of 800 MeV proton beam from PIP-II into the production target for Mu2e-II, assuming a targeting and μ production scenario similar to mu2e. The incoming beam trajectory must be modified from the mu2e parameters to match the focusing fields. Adding a vertical deflection at injection enables the injected beam to reach the target. Other differences from the mu2e system must be considered, including changes in the target structure, the radiation shielding and beam dump/absorber. H- beam should be stripped to p+. Other variations are discussed.

  11. The CDF SVX II upgrade for the Tevatron Run II

    International Nuclear Information System (INIS)

    Bortoletto, Daniela

    1997-01-01

    A microstrip silicon detector SVX II has been proposed for the upgrade of CDF to be installed in 1999 for Run II of the Tevatron. Three barrels of five layers of double-sided silicon microstrip detectors will cover the interaction region. A description of the project status will be presented. Emphasis will be given to the R and D program for silicon sensors which includes capacitance minimization, the study of coupling capacitor integrity, the operation of the detectors in conjunction with the SVXH and SVX2 readout chips in two beam tests and the determination of the detectors performance deterioration due to radiation damage

  12. EBR-II Data Digitization

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Su-Jong [Idaho National Lab. (INL), Idaho Falls, ID (United States); Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Sackett, John [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2014-08-01

    1. Objectives To produce a validation database out of those recorded signals it will be necessary also to identify the documents need to reconstruct the status of reactor at the time of the beginning of the recordings. This should comprehends the core loading specification (assemblies type and location and burn-up) along with this data the assemblies drawings and the core drawings will be identified. The first task of the project will be identify the location of the sensors, with respect the reactor plant layout, and the physical quantities recorded by the Experimental Breeder Reactor-II (EBR-II) data acquisition system. This first task will allow guiding and prioritizing the selection of drawings needed to numerically reproduce those signals. 1.1 Scopes and Deliverables The deliverables of this project are the list of sensors in EBR-II system, the identification of storing location of those sensors, identification of a core isotopic composition at the moment of the start of system recording. Information of the sensors in EBR-II reactor system was summarized from the EBR-II system design descriptions listed in Section 1.2.

  13. Human liver aldehyde dehydrogenase: coenzyme binding

    International Nuclear Information System (INIS)

    Kosley, L.L.; Pietruszko, R.

    1987-01-01

    The binding of [U- 14 C] NAD to mitochondrial (E2) and cytoplasmin(E1) aldehyde dehydrogenase was measured by gel filtration and sedimentation techniques. The binding data for NAD and (E1) yielded linear Scatchard plots giving a dissociation constant of 25 (+/- 8) uM and the stoichiometry of 2 mol of NAD bound per mol of E1. The binding data for NAD and (E2) gave nonlinear Scatchard plots. The binding of NADH to E2 was measured via fluorescence enhancement; this could not be done with E1 because there was no signal. The dissociation constant for E2 by this technique was 0.7 (+/- 0.4) uM and stoichiometry of 1.0 was obtained. The binding of [U- 14 C] NADH to (E1) and (E2) was also measured by the sedimentation technique. The binding data for (E1) and NADH gave linear Scatchard plots giving a dissociation constant of 13 (+/- 6) uM and the stoichiometry of 2.0. The binding data for NADH to (E2) gave nonlinear Scatchard plots. With (E1), the dissociation constants for both NAD and NADH are similar to those determined kinetically, but the stoichiometry is only half of that found by stopped flow technique. With (E2) the dissociation constant by fluorometric procedure was 2 orders of magnitude less than that from catalytic reaction

  14. 2-Methylbutyryl-coenzyme A dehydrogenase deficiency

    DEFF Research Database (Denmark)

    Sass, Jörn Oliver; Ensenauer, Regina; Röschinger, Wulf

    2008-01-01

    2-Methylbutyryl-CoA dehydrogenase (MBD; coded by the ACADSB gene) catalyzes the step in isoleucine metabolism that corresponds to the isovaleryl-CoA dehydrogenase reaction in the degradation of leucine. Deficiencies of both enzymes may be detected by expanded neonatal screening with tandem...... individuals showed clinical symptoms attributable to MBD deficiency although the defect in isoleucine catabolism was demonstrated both in vivo and in vitro. Several mutations in the ACADSB gene were identified, including a novel one. MBD deficiency may be a harmless metabolic variant although significant...

  15. Coenzyme recognition in para-hydroxybenzoate hydroxylase

    NARCIS (Netherlands)

    Eppink, M.H.M.

    1999-01-01

    Biochemistry is the science that studies the chemistry of life. This 'biological' chemistry includes growth, differentiation, movement, conductivity, immunity, transport and storage. During these processes proteins play an important role. The building blocks of proteins are amino acids, of

  16. RTNS-II: present status

    International Nuclear Information System (INIS)

    Heikkinen, D.W.; Logan, C.M.

    1980-10-01

    The present status of the RTNS-II facility is described and typical operating parameters are given. A brief discussion is given of the methods used in production of the TiT 2 targets as well as their performance and tritium handling at RTNS-II. The various types of non-interactive beam diagnostics presently in use at the neutron sources are outlined. The on-line computer system which provides a time history of an irradiation and records target performance is described. Examples are listed of several representative experimental programs which have been carried out thus far at RTNS-II. These include both active and passive experiments. Finally, several of the major improvements to the facility made since the beginning of the experimental program are given

  17. STARFIRE-II studies. Summary

    International Nuclear Information System (INIS)

    Baker, C.C.; Brooks, J.N.; Ehst, D.A.; Smith, D.L.; Sze, D.K.

    1985-01-01

    The US Department of Energy's Office of Fusion Energy has initiated several studies during FY-1985 called Tokamak Power System Studies (TPSS). The TPSS is being carried out by several laboratories, universities and industry with the general objective of developing innovative physics and technology concepts to improve the commercial attractiveness of tokamak power reactors. The effort of Argonne National Laboratory, entitled STARFIRE-II, is an effort to update and improve STARFIRE, which was the last comprehensive conceptual design study in the US of a commercial tokamak power plant. The STARFIRE-II effort has developed a number of goals in order to improve fusion commercial power plants based in part on several recent studies. The primary goals for STARFIRE-II are listed

  18. First results from SAGE II

    International Nuclear Information System (INIS)

    Abdurashitov, J.N.; Faizov, E.L.; Gavrin, V.N.

    1994-01-01

    The Russian-American Gallium solar neutrino Experiment (SAGE) began the second phase of operation (SAGE II) in September of 1992. Monthly measurements of the integral flux of solar neutrinos have been made with 55 tonnes of gallium. The K-peak results of the first five runs of SAGE II give a capture rate of 76 -18 +21 (stat) -7 +5 (sys) SNU. combined with the SAGE I result, the capture rate is 74 -12 +13 (stat) -7 +5 (sys) SNU. This represents only 56%--60% of the capture rate predicted by different Standard Solar Models

  19. Facilities design for TIBER II

    International Nuclear Information System (INIS)

    Thomson, S.L.; Blevins, J.D.

    1987-01-01

    This paper describes the conceptual design of the reactor building and reactor maintenance building for the TIBER II tokamak. These buildings are strongly influenced by the reactor configuration, and their characterization allows a better understanding of the economic and technical implications of the reactor design. Key features of TIBER II that affect the facilities design are the small size and compact arrangement, the use of an external vacuum vessel, and the complete reliance on remote maintenance. The building design incorporates requirements for equipment layout, maintenance operations and equipment, safety, and contamination control. 4 figs

  20. First results from SAGE II

    International Nuclear Information System (INIS)

    Aburashitov, J.N.; Faizov, E.L.; Gavrin, V.N.; Gusev, A.O.; Kalikhov, A.V.; Knodel, T.V.; Knyshenko, I.I.; Kornoukhov, V.N.; Mirmov, I.N.; Pshukov, A.M.; Shalagin, A.M.; Shikhin, A.A.; Timofeyev, P.V.; Veretenkin, E.P.; Vermul, V.M.; Zatsepin, G.T.; Bowles, T.J.; Nico, J.S.; Teasdale, W.A.; Wark, D.L.; Wilkerson, J.F.; Cleveland, B.T.; Daily, T.; Davis, R. Jr.; Lande, K.; Lee, C.K.; Wildenhain, P.W.; Elliott, S.R.; Cherry, M.L.

    1995-01-01

    The Russian-American Gallium solar neutrino Experiment (SAGE) began the second phase of operation (SAGE II) in September of 1992. Monthly measurements of the integral flux of solar neutrinos have been made with 55 tonnes of gallium. The K-peak results of the first five runs of SAGE II give a capture rate of 76 +21 -18 (stat) +5 -7 (sys) SNU. Combined with the SAGE I result, the capture rate is 74 +13 -12 (stat) +5 -7 (sys) SNU. This represents only 56%--60% of the capture rate predicted by different Standard Solar Models. copyright 1995 American Institute of Physics