ubiquinone and Disease

Coenzyme Q10 (CoQ10) or ubiquinone was known for its key role in mitochondrial bioenergetics as electron and proton carrier; later studies demonstrated its presence in other cellular membranes and in blood plasma, and extensively investigated its antioxidant role. These two functions constitute the basis for supporting the clinical indication of CoQ10. Furthermore, recent data indicate that CoQ10 affects expression of genes involved in human cell signalling, metabolism and transport and some of the effects of CoQ10 supplementation may be due to this property. CoQ10 deficiencies are due to autosomal recessive mutations, mitochondrial diseases, ageing-related oxidative stress and carcinogenesis processes, and also a secondary effect of statin treatment. Many neurodegenerative disorders, diabetes, cancer, fibromyalgia, muscular and cardiovascular diseases have been associated with low CoQ10 levels. CoQ10 treatment does not cause serious adverse effects in humans and new formulations have been developed that increase CoQ10 absorption and tissue distribution. Oral CoQ10 treatment is a frequent mitochondrial energizer and antioxidant strategy in many diseases that may provide a significant symptomatic benefit.

Topics: Disease; Humans; Therapeutics; Ubiquinone

The literature concerning the importance of coenzyme Q10 in health and disease has been reviewed. Usual dietary intake together with normal in vivo synthesis seems to fulfil the demands for Q10 in healthy individuals. The importance of Q10 supplementation for general health has not been investigated in controlled experiments. The literature allows no firm conclusions about the significance of Q10 in physical activity. In different cardiovascular diseases, including cardiomyopathy, relatively low levels of Q10 in myocardial tissue have been reported. Positive clinical and haemodynamic effects of oral Q10 supplementation have been observed in double-blind trials, especially in chronic heart failure. These effects should be further examined. No important adverse effects have been reported from experiments using daily supplements of up to 200 mg Q10 for 6-12 months and 100 mg daily for up to 6 y.

Topics: Cardiovascular Diseases; Dietary Supplements; Disease; Health; Humans; Neoplasms; Ubiquinone

During the present century there has been a dramatic change in life expectancy in advanced societies, now exceeding 80 years. As distinct from life expectancy, life potential is said to be at least 120 years, so that the continuing increase in knowledge has the potential for further major changes in the survival of humans conceivably in the near future. This presentation will be concerned with one aspect of the development of biomedical advances related in part to a concept of an "age-related universality of bioenergetic disease," and its potential amelioration and proposed impact on age-related disease and lifestyle. Aging is a complex biological process associated with a progressive decline in the physiological and biochemical performance of individual tissues and organs, leading to age-associated disease and senescence. Consideration of the progressive accumulation of mitochondrial DNA mutation with age and the tissue/cellular bioenergy decline associated with the aging process has led us to the proposal of a "universality of bioenergetic disease" and the potential for a redox therapy for the condition. This concept envisages that a tissue-bioenergetic decline will be intrinsic to various diseases of the aged and thereby contribute to their pathology, in particular, heart failure, degenerative brain disease, muscle and vascular diseases, as well as other syndromes. The information and concepts embodied in this proposal will be reviewed under the following headings: (1) mitochondrial DNA deletion mutation in some tissue is very extensive and shows mosaicism; (2) age-associated tissue/cellular bioenergy mosaic closely corresponds to the mtDNA profile; (3) cellular bioenergy as a function of mitochondrial bioenergy, glycolysis, and plasma membrane oxidoreductase; (4) redox therapy for the reenergization of cells, tissues, and whole organs. A redox therapy based on coenzyme Q10 has demonstrated profound alteration in heart function of old rats; no significant effect was observed with young rats.

Topics: Aged; Aged, 80 and over; Aging; Animals; Coenzymes; Disease; DNA, Mitochondrial; Heart; Humans; Life Expectancy; Mosaicism; Point Mutation; Rats; Sequence Deletion; Therapeutics; Ubiquinone

Ubiquinone (Q) shares its biological implication in membrane-associated redox reactions with a variety of other redox carriers, such as dehydrogenases, non-heme-iron proteins, and cytochromes. Peculiarities arise from the lack of transition metals, which in contrast to the other electron carriers do not participate in redox-shuttle activities of Q. Another peculiarity is the lipophilicity of Q, which allows free movement between reductants and oxidants of a membrane. The chemistry of Q reduction and ubiquinol oxidation requires the stepwise acceptance and transfer of two single electrons associated with the addition or release of two single H+. These special qualities are widely used in biological membranes for linear electron transfer and transmembranous H+ translocation. In mitochondria it was long reported that under certain conditions linear e- transfer from the semireduced form (SQ.) to native oxidants of the respiratory chain may run out of control, thereby establishing a permanent source of oxygen radical release. It should be mentioned that in mitochondria e- transfer to dioxygen out of sequence requires a particular treatment with inhibitors and uncouplers of the respiratory chain. Nevertheless, it is generally assumed that Q is mainly involved in mitochondrial O2.- generation and that mitochondria represent the major source of O2.- radicals under physiological and various pathophysiological conditions. The ever-increasing application of coenzyme Q as an antioxidant for the prophylaxis and treatment of a great variety of functional disorders, including senescence, has considerably stimulated our interest in the potential prooxidative potency of this natural electron carrier. Experimental evidence will be presented that under physiological conditions Q implicated in mitochondrial e- transfer of the respiratory chain is not involved in cellular oxygen activation. It will also be shown that alterations of Q from an e- carrier to an active radical promotor is possible under various conditions. In addition, reaction products emerging from the antioxidant activity of ubiquinol were found to stimulate the formation of inorganic as well as organic oxygen radicals.

Topics: Aging; Animals; Disease; Electron Transport; Humans; Membrane Fluidity; Mitochondria; Models, Biological; Oxidation-Reduction; Oxidative Stress; Oxygen Consumption; Ubiquinone

This presentation is a brief review of current knowledge concerning some biochemical, physiological and medical aspects of the function of ubiquinone (coenzyme Q) in mammalian organisms. In addition to its well-established function as a component of the mitochondrial respiratory chain, ubiquinone has in recent years acquired increasing attention with regard to its function in the reduced form (ubiquinol) as an antioxidant. Ubiquinone, partly in the reduced form, occurs in all cellular membranes as well as in blood serum and in serum lipoproteins. Ubiquinol efficiently protects membrane phospholipids and serum low-density lipoprotein from lipid peroxidation, and, as recent data indicate, also mitochondrial membrane proteins and DNA from free-radical induced oxidative damage. These effects of ubiquinol are independent of those of exogenous antioxidants, such as vitamin E, although ubiquinol can also potentiate the effect of vitamin E by regenerating it from its oxidized form. Tissue ubiquinone levels are regulated through the mevalonate pathway, increasing upon various forms of oxidative stress, and decreasing during aging. Drugs inhibiting cholesterol biosynthesis via the mevalonate pathway may inhibit or stimulate ubiquinone biosynthesis, depending on their site of action. Administration of ubiquinone as a dietary supplement seems to lead primarily to increased serum levels, which may account for most of the reported beneficial effects of ubiquinone intake in various instances of experimental and clinical medicine.

Topics: Animals; Antioxidants; Disease; DNA Damage; Electron Transport Complex III; Electron Transport Complex IV; Humans; Lipid Peroxidation; Lipoproteins, LDL; Mammals; Membrane Lipids; Membrane Proteins; Models, Biological; NAD(P)H Dehydrogenase (Quinone); Organ Specificity; Oxidants; Oxidation-Reduction; Phospholipids; Reference Values; Ubiquinone

Large-scale phenotyping projects such as the Sanger Mouse Genetics project are ongoing efforts to help identify the influences of genes and their modification on phenotypes. Gene-phenotype relations are crucial to the improvement of our understanding of human heritable diseases as well as the development of drugs. However, given that there are ∼: 20 000 genes in higher vertebrate genomes and the experimental verification of gene-phenotype relations requires a lot of resources, methods are needed that determine good candidates for testing.. In this study, we applied an association rule mining approach to the identification of promising secondary phenotype candidates. The predictions rely on a large gene-phenotype annotation set that is used to find occurrence patterns of phenotypes. Applying an association rule mining approach, we could identify 1967 secondary phenotype hypotheses that cover 244 genes and 136 phenotypes. Using two automated and one manual evaluation strategies, we demonstrate that the secondary phenotype candidates possess biological relevance to the genes they are predicted for. From the results we conclude that the predicted secondary phenotypes constitute good candidates to be experimentally tested and confirmed.. The secondary phenotype candidates can be browsed through at http://www.sanger.ac.uk/resources/databases/phenodigm/gene/secondaryphenotype/list.. ao5@sanger.ac.uk or ds5@sanger.ac.uk. Supplementary data are available at Bioinformatics online.

Topics: Animals; Ataxia; Data Mining; Disease; Genes; Humans; Mice; Mitochondrial Diseases; Muscle Weakness; Phenotype; Ubiquinone

The concentration of antioxidants in human blood plasma is important in investigating and understanding the relationship between diet, oxidant stress, and human disease. The HPLC-EC technique combines selectivity with high sensitivity for measuring both water- and lipid-soluble antioxidants. The excellent sensitivity of the methods described here allows one to measure a panel of antioxidants in a small volume of plasma.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Bilirubin; Blood Chemical Analysis; Blood Proteins; Carotenoids; Chromatography, High Pressure Liquid; Diet; Disease; Electrochemistry; Humans; Indicators and Reagents; Lycopene; Sulfhydryl Compounds; Ubiquinone; Uric Acid; Vitamin E