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1.
In this communication, the concept is developed that coenzyme Q10 has a toti-potent role in the regulation of cellular metabolism. The redox function of coenzyme Q10 leads to a number of outcomes with major impacts on sub-cellular metabolism and gene regulation. Coenzyme Q10's regulatory activities are achieved in part, through the agency of its localization in the various sub-cellular membrane compartments. Its fluctuating redox poise within these membranes reflects the cell's metabolic micro-environments. As an integral part of this process, H2O2 is generated as a product of the normal electron transport systems to function as a mitogenic second messenger informing the nuclear and mitochondrial (chloroplast) genomes on a real-time basis of the status of the sub-cellular metabolic micro-environments and the needs of that cell. Coenzyme Q10 plays a major role both in energy conservation, and energy dissipation as a component of the uncoupler protein family. Coenzyme Q10 is both an anti-oxidant and a pro-oxidant and of the two the latter is proposed as its more important cellular function. Coenzyme Q10 has been reported, to be of therapeutic benefit in the treatment of a wide range of age related degenerative systemic diseases and mitochondrial disease. Our over-arching hypotheses on the central role played by coenzyme Q10 in redox poise changes, the generation of H2O2, consequent gene regulation and metabolic flux control may account for the wide ranging therapeutic benefits attributed to coenzyme Q10. 相似文献
2.
Quinones (e.g., coenzyme Q, CoQ10) are best known as carriers of electrons and protons during oxidative phosphorylation and photosynthesis. A myriad of mostly more indirect physical methods, including fluorescence spectroscopy, electron-spin resonance, and nuclear magnetic resonance, has been used to localize CoQ10 within lipid membranes. They have yielded equivocal and sometimes contradictory results. Seeking unambiguous evidence for the localization of ubiquinone within lipid bilayers, we have employed neutron diffraction. CoQ10 was incorporated into stacked bilayers of perdeuterated dimyristoyl phosphatidyl choline doped with dimyristoyl phosphatidyl serine containing perdeuterated chains in the natural fluid-crystalline state. Our data show CoQ10 at the center of the hydrophobic core parallel to the membrane plane and not, as might be expected, parallel to the lipid chains. This localization is of importance for its function as a redox shuttle between the respiratory complexes and, taken together with our recent result that squalane is in the bilayer center, may be interpreted to show that all natural polyisoprene chains lie in the bilayer center. Thus ubiquinone, in addition to its free radical scavenging and its well-known role in oxidative phosphorylation as a carrier of electrons and protons, might also act as an inhibitor of transmembrane proton leaks. 相似文献
3.
4.
Kiselev MA Ryabova NY Balagurov AM Dante S Hauss T Zbytovska J Wartewig S Neubert RH 《European biophysics journal : EBJ》2005,34(8):1030-1040
The structure and hydration of a stratum corneum (SC) lipid model membrane composed of N-(-hydroxyoctadecanoyl)-phytosphingosine (CER6)/cholesterol (Ch)/palmitic acid (PA)/cholesterol sulfate (ChS) were characterized by neutron diffraction. The neutron scattering length density across the SC lipid model membrane was calculated from measured diffraction peak intensities. The internal membrane structure and water distribution function across the bilayer were determined. The low hydration of the intermembrane space is a major feature of the SC lipid model membrane. The thickness of the water layer in the SC lipid model membrane is about 1 Å at full hydration. For the composition 55% CER6/25% Ch/15% PA/5% ChS, in a partly dehydrated state (60% humidity) and at 32°C, the lamellar repeat distance and the membrane thickness have the same value of 45.6 Å . The hydrophobic region of the membrane has a thickness of 31.2 Å . A decrease of the Ch content increases the membrane thickness. The water diffusion through the SC lipid model multilamellar membrane is a considerably slow process relative to that through phospholipid membranes. In excess water, the membrane hydration follows an exponential law with two characteristic times of 93 and 44 min. At 81°C and 97% humidity, the membrane separates into two phases with repeat distances of 45.8 and 40.5 Å . Possible conformations of CER6 molecules in the dry and hydrated multilayers are discussed. 相似文献
5.
Suk-Jin Ha Sang-Yong Kim Jin-Ho Seo Won-Il Sim Hee-Jung Moon Jung-Kul Lee 《World journal of microbiology & biotechnology》2008,24(6):887-890
By the optimization of nitrogen source for coenzyme Q10 (ubiquinone, CoQ10) production in Agrobacterium tumefaciens KCCM 10413 culture, the highest CoQ10 production was achieved in medium containing corn steep powder (CSP). Components for a stimulatory effect on the production
of CoQ10 in CSP were screened, and lactate was found to increase dry cell weight (DCW) and the specific CoQ10 content. In a fed-batch culture of A. tumefaciens, supplementation with 1.5 g of lactate l−1 further improved DCW, the specific CoQ10 content, and CoQ10 production by 16.0, 5.8, and 22.8%, respectively. It has been reported that lactate stimulates cell growth and acts as an
accelerator driving the tricarboxylic acid (TCA) cycle (Roberto et al. 2002, Biotechnol Let 24:427–431; Matsuoka et al. 1996, Biosci Biotechnol Biochem 60:575–579). In this study, lactate supplementation increased DCW and the specific CoQ10 content in A. tumefaciens culture, probably by accelerating TCA cycle and energy production as reported previously, leading to the increase of CoQ10 production. 相似文献
6.
A novel polarographic method for the determination of coenzyme Q(10) in beta-cyclodextrin (beta-CD) and iodinate system is proposed. The stability of coenzyme Q(10) to light was improved by the formation of coenzyme Q(10)-beta-CD inclusion complex. In addition, the sensitivity for the determination of coenzyme Q(10) was enhanced by both the formation and the polarographic catalytic wave of the inclusion complex in the presence of iodinate. In 0.1 mol/L HAc-NaAc (pH 4.7)-5.0 x 10(-5) mol/L beta-CD-1.2 x 10(-3) mol/L potassium iodinate-ethanol/water (60:40, v/v) medium, coenzyme Q(10)-beta-CD inclusion complex yielded a sensitive association/parallel catalytic wave. The second-order derivative peak current of the catalytic wave was proportional to coenzyme Q(10) concentration in the range of 6.0 x 10(-8)-2.5 x 10(-7) mol/L, and the detection limit was 1.0 x 10(-8) mol/L. The proposed method has high analytical sensitivity and is allowed to determine coenzyme Q(10) under light. 相似文献
7.
An increasing amount of experimental and epidemiological evidence implicates the involvement of oxygen derived radicals in the pathogenesis of cancer development. It is well known that chemical carcinogenesis is multistage process. Free radicals are found to be involved in both initiation and promotion of multistage carcinogenesis. Tamoxifen (TAM) is a potent antioxidant and a non-steroidal antiestrogen drug most used in the chemotherapy and chemoprevention of breast cancer. Besides its anticarcinogenic potential, it also produces some adverse toxic side effects, while taken for a long time. In order to minimise the side effects and to improve the antioxidant efficacy of tamoxifen, coenzyme Q10 (CoQ10) was added. Hence the present study was designed to investigate the combined efficacy of TAM along with CoQ10 in 7, 12 dimethyl benz(a)anthracene (DMBA) induced peroxidative damage in rat mammary carcinoma. The experimental setup comprised of one control and five experimental groups and it was carried out in adult female Sprague-Dawley rats. Mammary carcinoma was induced by oral administration of DMBA (25 mg kg–1 body wt) and the treatment was started by the oral administration of TAM (10 mg kg–1 body wt day–1) and CoQ10 (40 mg kg–1 body wt day–1) dissolved in olive oil and continued for 28 days. Rats induced with DMBA showed a decline in the thiol capacity of the cell accompanied by high malondialdehyde content levels along with lowered activities of antioxidant status (superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione). In contrast, glutathione metabolising enzymes (glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione-S-transferase) were increased significantly in chemically induced carcinoma bearing rats. Administration of TAM along with CoQ10 restored the activities to a significant level thereby preventing cancer cell proliferation. This study highlights the increased antioxidant enzyme activities in relation to the susceptibility of cells to carcinogenic agents and the response of tumour cells to the chemotherapeutic agents. 相似文献
8.
Theresa P.T. Nguyen Alberto Casarin Maria Andrea Desbats Mara Doimo Eva Trevisson Carlos Santos-Ocaña Placido Navas Catherine F. Clarke Leonardo Salviati 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2014,1841(11):1628-1638
Coq5 catalyzes the only C-methylation involved in the biosynthesis of coenzyme Q (Q or ubiquinone) in humans and yeast Saccharomyces cerevisiae. As one of eleven polypeptides required for Q production in yeast, Coq5 has also been shown to assemble with the multi-subunit complex termed the CoQ-synthome. In humans, mutations in several COQ genes cause primary Q deficiency, and a decrease in Q biosynthesis is associated with mitochondrial, cardiovascular, kidney and neurodegenerative diseases. In this study, we characterize the human COQ5 polypeptide and examine its complementation of yeast coq5 point and null mutants. We show that human COQ5 RNA is expressed in all tissues and that the COQ5 polypeptide is associated with the mitochondrial inner membrane on the matrix side. Previous work in yeast has shown that point mutations within or adjacent to conserved COQ5 methyltransferase motifs result in a loss of Coq5 function but not Coq5 steady state levels. Here, we show that stabilization of the CoQ-synthome within coq5 point mutants or by over-expression of COQ8 in coq5 null mutants permits the human COQ5 homolog to partially restore coq5 mutant growth on respiratory media and Q6 content. Immunoblotting against the human COQ5 polypeptide in isolated yeast mitochondria shows that the human Coq5 polypeptide migrates in two-dimensional blue-native/SDS-PAGE at the same high molecular mass as other yeast Coq proteins. The results presented suggest that human and Escherichia coli Coq5 homologs expressed in yeast retain C-methyltransferase activity but are capable of rescuing the coq5 yeast mutants only when the CoQ-synthome is assembled. 相似文献
9.
Kessner D Kiselev MA Hauss T Dante S Wartewig S Neubert RH 《European biophysics journal : EBJ》2008,37(6):1051-1057
This letter presents our first results in using the benefit of selective deuteration in neutron diffraction studies on stratum
corneum (SC) lipid model systems. The SC represents the outermost layer of the mammalian skin and exhibits the main skin barrier.
It is essential for studying drug penetration through the SC to know the internal structure and hydration behaviour on the
molecular level. The SC intercellular matrix is mainly formed by ceramides (CER), cholesterol (CHOL) and long- chain free
fatty acids (FFA). Among them, CHOL is the most abundant individual lipid, but a detailed knowledge about its localisation
in the SC lipid matrix is still lacking. The structure of the quaternary SC lipid model membranes composed of either CER[AP]/CHOL-D6/palmitic
acid (PA)/cholesterol sulphate (ChS) or CER[AP]/CHOL-D7/PA/ChS is characterized by neutron diffraction. Neutron diffraction
patterns from the oriented samples are collected at the V1 diffractometer of the Hahn-Meitner-Institute, Berlin, measured
at 32°C, 60% humidity and at different D2O contents. The neutron scattering length density profile in the direction normal to the surface is restored by Fourier synthesis
from the experimental diffraction patterns. The analysis of scattering length density profile is a suitable tool for investigating
the internal structure of the SC lipid model membranes. The major finding is the experimental proof of the CHOL localisation
in SC model membrane by deuterium labelling at prominent positions in the CHOL molecules. 相似文献
10.
Assay of coenzyme Q(10) in plasma by a single dilution step 总被引:2,自引:0,他引:2
A new method is described for determining coenzyme Q(10) (CoQ(10)) in plasma. The method is based on oxidation of CoQ(10) in the sample by treating it with para-benzoquinone followed by extraction with 1-propanol and direct injection into the HPLC apparatus. This method achieves a linear detector response for peak area measurements over the concentration range of 0.05-3.47 microM. Diode array analysis of the peak was consistent with CoQ(10) spectrum. Supplementation of the samples with known amounts of CoQ(10) yielded a quantitative recovery of 96-98.5%; the method showed a level of quantitation of 1.23 nmol per HPLC injection (200 microl of propanol extract containing 33.3 microl of plasma). A correlation of r = 0.99 (P < 0.0001) was found with a reference electrochemical detection method. Within run precision showed a CV% of 1.6 for samples approaching normal values (1.02 microM). Day-to-day precision was also close to 2%. 相似文献
11.
Preparation and characterization of novel coenzyme Q<Subscript>10</Subscript> nanoparticles engineered from microemulsion precursors 总被引:2,自引:0,他引:2
The purpose of these studies was to prepare and characterize nanoparticles into which Coenzyme Q10 (CoQ10) had been incorporated (CoQ10-NPs) using a simple and potentially scalable method. CoQ10-NPs were prepared by cooling warm microemulsion precursors composed of emulsifying wax, CoQ10, Brij 78, and/or Tween 20. The nanoparticles were lyophilized, and the stability of CoQ10-NPs in both lyophilized form and aqueous suspension was monitored over 7 days. The release of CoQ10 from the nanoparticles was investigated at 37°C. Finally, an in vitro study of the uptake of CoQ10-NPs by mouse macrophage, J774A.1, was completed. The incorporation efficiency of CoQ10 was approximately 74%±5%. Differential Scanning Calorimetry (DSC) showed that the nanoparticle was not a physical mixture
of its individual components. The size of the nanoparticles increased over time if stored in aqueous suspension. However,
enhanced stability was observed when the nanoparticles were stored at 4°C. Storage in lyophilized form demonstrated the highest
stability. The in vitro release profile of CoQ10 from the nanoparticles showed an initial period of rapid release in the first 9 hours followed by a period of slower and
extended release. The uptake of CoQ10-NPs by the J774A.1 cells was over 4-fold higher than that of the CoQ10-free nanoparticles (P<.05). In conclusion, CoQ10-NPs with potential application for oral CoQ10 delivery were engineered readily from microemulsion precursors. 相似文献
12.
《Free radical research》2013,47(11):1338-1344
AbstractDespite their being good markers of oxidative stress for clinical use, little is known about ubiquinol-10 (reduced coenzyme Q10) and ubiquinone-10 (oxidized coenzyme Q10) levels in foetuses and their mothers. This study investigates oxidative stress in 10 healthy maternal venous, umbilical arterial and venous bloods after vaginal delivery by measuring ubiquinol-10 and ubiquinone-10 levels. Serum ubiquinol-10 and ubiquinone-10 levels were measured by HPLC with a highly sensitive electrochemical detector. Maternal venous ubiquinol-10 and ubiquinone-10 levels were significantly higher than umbilical arterial and venous levels (all p < 0.001). However, the ubiquinone-10/total coenzyme Q10 (CoQ10) ratio, which reflects the redox status, was significantly higher in umbilical arterial and umbilical venous blood compared to maternal venous blood (all p < 0.001). The ubiquinone-10/total CoQ10 ratio was higher in umbilical arterial than in umbilical venous blood (p < 0.01). The present study demonstrated that foetuses were under higher oxidative stress than their mothers. 相似文献
13.
Armen Y. Mulkidjanian 《BBA》2005,1709(1):5-34
This review is focused on the mechanism of ubiquinol oxidation by the cytochrome bc1 complex (bc1). This integral membrane complex serves as a “hub” in the vast majority of electron transfer chains. The bc1 oxidizes a ubiquinol molecule to ubiquinone by a unique “bifurcated” reaction where the two released electrons go to different acceptors: one is accepted by the mobile redox active domain of the [2Fe-2S] iron-sulfur Rieske protein (FeS protein) and the other goes to cytochrome b. The nature of intermediates in this reaction remains unclear. It is also debatable how the enzyme prevents short-circuiting that could happen if both electrons escape to the FeS protein. Here, I consider a reaction mechanism that (i) agrees with the available experimental data, (ii) entails three traits preventing the short-circuiting in bc1, and (iii) exploits the evident structural similarity of the ubiquinone binding sites in the bc1 and the bacterial photosynthetic reaction center (RC). Based on the latter congruence, it is suggested that the reaction route of ubiquinol oxidation by bc1 is a reversal of that leading to the ubiquinol formation in the RC. The rate-limiting step of ubiquinol oxidation is then the re-location of a ubiquinol molecule from its stand-by site within cytochrome b into a catalytic site, which is formed only transiently, after docking of the mobile redox domain of the FeS protein to cytochrome b. In the catalytic site, the quinone ring is stabilized by Glu-272 of cytochrome b and His-161 of the FeS protein. The short circuiting is prevented as long as: (i) the formed semiquinone anion remains bound to the reduced FeS domain and impedes its undocking, so that the second electron is forced to go to cytochrome b; (ii) even after ubiquinol is fully oxidized, the reduced FeS domain remains docked to cytochrome b until electron(s) pass through cytochrome b; (iii) if cytochrome b becomes (over)reduced, the binding and oxidation of further ubiquinol molecules is hampered; the reason is that the Glu-272 residue is turned towards the reduced hemes of cytochrome b and is protonated to stabilize the surplus negative charge; in this state, this residue cannot participate in the binding/stabilization of a ubiquinol molecule. 相似文献
14.
Uffe Bernchou Jensen 《生物化学与生物物理学报:生物膜》2005,1715(1):1-5
The behavior of a fluid supported membrane during hydrolysis by phospholipase A2 is for the first time visualized by time-resolved fluorescence imaging. After a lag phase, hydrolysis proceeds from the boundary of existing holes and via nucleation of new holes. During subsequent hydrolysis, the shape of the membrane boundary is determined both by hydrolysis and by shape relaxations due to the action of line tension. This is manifested by the appearance of Rayleigh instabilities in membrane rims and by an effect analogous to domain coarsening in phase transitions in which membrane holes decay when they are within a certain distance from larger and expanding holes. 相似文献
15.
Sofia Gallo 《Inorganica chimica acta》2007,360(1):360-368
The organometallic complex coenzyme B12 (adenosyl cobalamin, AdoCbl) is not only an essential coenzyme in many biochemical reactions of most if not all living organisms but has lately been shown to play a crucial role in the regulation of B12 related genes. As a consequence, coenzyme B12 has been a target of intense research. However, the investigations of AdoCbl have often been hampered due to its high light-sensitivity leading to decomposition of the compound within a few seconds. Here, we describe a strategy to synthesize more light-stable coenzyme B12 analogs, which show similar steric properties as adenosyl cobalamin. The synthesis, structural characterization as well as the pH dependent “base-on/base-off” behavior of cyanide bridged vitamin B12 conjugates with either a cis-[(NH3)2Pt]2+ or an [enPt]2+ moiety, leading to cis-[(NH3)2PtCl-vitB12]+ (1) and [enPtCl-vitB12]+ (2) are reported. The subsequent reaction of cis-[(NH3)2PtCl-vitB12]+ with the model nucleobase 9-methyladenine leads to the corresponding adduct, where the adenine moiety is coordinated to the Pt2+ center either via N1 or N7. This compound is light-stable and harbors the adenine moiety in the same distance of 5 Å above the corrin plane as present in the highly light-sensitive adenosyl cobalamin. 相似文献
16.
Kessner D Kiselev M Dante S Hauss T Lersch P Wartewig S Neubert RH 《European biophysics journal : EBJ》2008,37(6):989-999
The lipid matrix in stratum corneum (SC) plays a key role in the barrier function of the mammalian skin. The major lipids are ceramides (CER), cholesterol (CHOL) and free fatty acids (FFA). Especially the unique-structured omega-acylceramide CER[EOS] is regarded to be essential for skin barrier properties by inducing the formation of a long-periodicity phase of 130 angstroms (LPP). In the present study, the arrangement of CER[EOS], either mixed with CER[AP] and CHOL or with CER[AP], CHOL and palmitic acid (PA), inside a SC lipid model membrane has been studied for the first time by neutron diffraction. For a mixed CER[EOS]/CER[AP]/CHOL membrane in a partly dehydrated state, the internal membrane nanostructure, i.e. the neutron scattering length density profile in the direction normal to the surface, was obtained by Fourier synthesis from the experimental diffraction patterns. The membrane repeat distance is equal to that of the formerly used SC lipid model system composed of CER[AP]/CHOL/PA/ChS. By comparing both the neutron scattering length density profiles, a possible arrangement of synthetic long-chain CER[EOS] molecules inside a SC lipid model matrix is suggested. The analysis of the internal membrane nanostructure implies that one CER[EOS] molecule penetrates from one membrane layer into an adjacent layer. A 130 angstroms periodicity phase could not be observed under experimental conditions, either in CER/CHOL mixtures or in CER/CHOL/FFA mixture. CER[EOS] can be arranged inside a phase with a repeat unit of 45.2 angstroms which is predominately formed by short-chain CER[AP] with distinct polarity. 相似文献
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18.
Lucy P.L. van de Vijver Christine Weber Alwine F.M. Kardinaal Diederick E. Grobbee Hans M.G. Princen Geert van Poppel 《Free radical research》2013,47(3):165-172
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 been reported. To study the relation between unsupplemented concentrations of plasma CoQ10 and coronary atherosclerosis, we performed a case-control study among 71 male cases with angiographically documented severe coronary atherosclerosis and 69 healthy male controls free from symptomatic cardiovascular disease and without atherosclerotic plaques in the carotid artery.Plasma CoQ10 concentrations (mean ± SE) were 0.86 ± 0.04 vs. 0.83 ± 0.04 μmol/l for cases and controls, respectively. The CoQ10/LDL-cholesterol ratio (μmol/mmol) was slightly lower in cases than in controls (0.22 ± 0.01 vs. 0.26 ± 0.03). Differences in CoQ10 concentrations and CoQ10/LDL-cholesterol ratio did not reach significance. The odds ratios (95% confidence interval) for the risk of coronary atherosclerosis calculated per μmol/l increase of CoQ10 was 1.12 (0.28–4.43) after adjustment for age, smoking habits, total cholesterol and diastolic blood pressure.We conclude that an unsupplemented plasma CoQ10 concentration is not related to risk of coronary atherosclerosis. 相似文献
19.
K. Komoriya H. Ohmori A. Azuma S. Kurozumi Y. Hashimoto K.C. Nicolaou W.E. Barnette R.L. Magolda 《Prostaglandins & other lipid mediators》1978,15(4):557-564
Prostaglandin I2 potentiated the paw swelling induced by carrageenin in rats. Prostaglandin I2 (0.1 μg) showed similar activity to PGE1 (0.01 μg). This potentiating property disappeared in 60 minutes and was completely abolished by diphenhydramine (25 mg kg−1, i.p.). In vascular permeability tests, PGI2 itself (2.5 × 10−10 mol, 88 ng) caused no dye leakage reaction, but PGE1 (2.5 × 10−10 mol, 88.5 ng) caused a significant dye leakage. This effect of PGE1 was statistically significant compared with vehicle- or PGI2-treated group (p<0.05). Prostaglandin I2 potentiated the increased vascular permeability induced by 5-hydroxytriptamine (2.5 × 10−10 mol), bradykinin (5 × 10−10 mol) and histamine (2 × 10−10 to 2 × 10−8 mol). The potentiation was the most evidence in the case of histamine. 相似文献
20.
Summary A phenomenon associated with the aging process is a general age-dependent decline in cellular bioenergetic capacity that varies
from tissue to tissue and even from cell to cell within the same tissue. This variation eventually forms a tissue bioenergy
mosaic. Recent evidence by our group suggests that the accumulation of mitochondrial DNA mutations, in conjunction with a
concurrent decrease in full-length mtDNA in tissues such as skeletal and cardiac muscle, strongly correlates with decreased
mitochondrial function and accounts for the bioenergy mosaic. Evidence is also presented suggesting that amelioration with
coenzyme Q10 may restore some of the age-associated decline in bioenergy function, in effect providing the potential for a “redox therapy”.
Coenzyme Q is a naturally occurring material that is present in the membranes of all animal cells. Its primary function is
to act as an electron carrier in the mitochondrial electron transport chain enabling the energy from substrates such as fats
and sugars (in the form of reducing equivalents) to be ultimately captured in the form of ATP, which in turn may be utilised
as a source of cellular bioenergy. Coenzyme Q10 has no known toxic effects and has been used in a limited number of animal studies and human clinical trials; however, the
mechanism of action of coenzyme Q10 remains unclear. A series of experiments by this group aimed at determining the efficacy of coenzyme Q10 treatment on ameliorating the bioenergy capacity at the organ and cellular level will also be reviewed. 相似文献