ubiquinol and Disease

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

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