ubiquinone and hydroquinone

Since the term "cosmeceutical" was coined over 2 decades ago, the number of products in this category that claim to combat dermal aging has grown dramatically. Topical retinoids remain the mainstay for treating photoaging given their proven efficacy in both clinical and histologic outcomes. In addition to retinoids, many other cosmeceutical agents are now available. The proliferation of products can cause confusion among consumers, who often ask their dermatologist for advice as to which antiaging products they should choose. Ideally, the antiaging claims of cosmeceutical formulations and their components should be demonstrated in controlled clinical trials. In order to provide appropriate recommendations to their patients, dermatologists must become familiar with the available data on currently marketed products and gain experience with antiaging regimens. This review discusses the efficacy of a number of currently marketed drug products with proven photoaging benefits and cosmeceutical products that claim similar benefits. Among the agents discussed are single-entity and combination products containing hydroquinones, retinoids, topical antioxidants, and minerals.

Topics: Administration, Topical; Antioxidants; Benzoquinones; Cosmetics; Dermatologic Agents; Drug Combinations; Humans; Hydroquinones; Retinoids; Skin Aging; Tretinoin; Ubiquinone

Phase II conjugation of phenolic compounds constitutes an important mechanism through which exogenous or endogenous toxins are detoxified and excreted. Species differences in the rates of glucuronidation or sulfation can lead to significant variation in the metabolism of this class of compounds. Conjugation of the hydroxyl groups of phenols can occur with glucuronate or sulfate. Quinone metabolism, deactivation, and detoxification are also affected by the same conjugatory systems as phenols; however, reduction of quinones to hydroquinols seems to be a prerequisite. This work reviews current knowledge on phenol conjugation and its implications on hydroquinone metabolism with special consideration for coenzyme Q metabolism.

Topics: Animals; Glucuronides; Glucuronosyltransferase; Humans; Hydroquinones; Phenols; Sulfotransferases; Ubiquinone; Uridine Diphosphate Glucuronic Acid

This report summarizes new evidence for a plasma-membrane-associated hydroquinone oxidase designated as CNOX (constitutive plasma membrane NADH oxidase) that functions as a terminal oxidase for a plasma membrane oxidoreductase (PMOR) electron transport chain to link the accumulation of lesions in mitochondrial DNA to cell-surface accumulations of reactive oxygen species. Previous considerations of plasma membrane redox changes during aging have lacked evidence for a specific terminal oxidase to catalyze a flow of electrons from cytosolic NADH to molecular oxygen (or to protein disulfides). Cells with functionally deficient mitochondria become characterized by an anaerobic metabolism. As a result, NADH accumulates from the glycolytic production of ATP. Elevated PMOR activity has been shown to be necessary to maintain the NAD(+)/NADH homeostasis essential for survival. Our findings demonstrate that the hyperactivity of the PMOR system results in an NADH oxidase (NOX) activity capable of generating reactive oxygen species at the cell surface. This would serve to propagate the aging cascade both to adjacent cells and to circulating blood components. The generation of superoxide by NOX forms associated with aging is inhibited by coenzyme Q and provides a rational basis for the anti-aging activity of circulating coenzyme Q.

Topics: Animals; Cell Membrane; Cellular Senescence; Humans; Hydroquinones; Multienzyme Complexes; NAD; NADH, NADPH Oxidoreductases; Oxidative Stress; Ubiquinone

This paper will address two aspects regarding the antioxidative role of coenzyme Q (CoQ): (1) Is the antioxidant function of CoQ primary or secondary (coincidental), i.e. was this molecule selected during evolution to function primarily as an essential functional component of the mitochondrial electron transfer chain and oxidative phosphorylation processes, is its antioxidative capability merely a coincidence of its hydroquinone structure, or was its synthetic enzyme sequence selected on the basis of the advantage to the evolving organism of both functions of CoQ? (2) What is the mechanism whereby the hydroquinone (antioxidant) form of CoQ (CoQH2) is maintained in high proportion in the various and many membranes in which it resides, and in which an obvious electron transfer mechanism to reduce it is not present? The essentiality of the antioxidative role of CoQH2 will be explored and compared to other primary and secondary antioxidants. Recent evidence implicating the two-electron quinone reductase, DT-diaphorase, in the maintenance of the reduced, antioxidant state of CoQ during the oxidative stress of exhaustive exercise will be presented, and a hypothesis concerning the evolutionary significance of DT-diaphorase will be offered.

Topics: Animal Population Groups; Animals; Antioxidants; Dicumarol; Electron Transport; Hydroquinones; Lipid Peroxidation; Male; NAD(P)H Dehydrogenase (Quinone); Oxidative Phosphorylation; Oxidative Stress; Plant Physiological Phenomena; Rats; Rats, Sprague-Dawley; Ubiquinone

The current model of the protonmotive ubiquinone cycle as applied to mitochondrial ubiquinol-cytochrome c reductase complex (Complex III) is able to explain a number of previously puzzling observations concerning electron-transfer and proton translocating functions of the complex. However, a number of pertinent experimental observations concerning the structure and function of this complex cannot as yet be incorporated into the present version of the ubiquinone cycle. The yet unresolved problems of electron transfer uncovered by these observations include some kinetic and thermodynamic problems, uncertainties in the binding site(s) and mode of binding of ubiquinol and inhibitors, the observed multiple spectroscopic, electrochemical, and kinetic forms of cytochromes b, iron-sulfur protein, and cytochrome c1, the multiple and overlapping effects of inhibitors, and the functional role of conformational changes in the complex. It is concluded that although the Q cycle is a valuable base for the design of future experiments, its mechanism must be reconciled with the above uncertainties as well as with the accumulated evidence that Complex III can exist in two or more interchangeable forms, exhibiting different properties with respect to electron-transfer pathways, inhibitor binding, and spectral and electrochemical properties of the electron-carrier subunits.

Topics: Animals; Carrier Proteins; Coenzymes; Cytochrome b Group; Electron Transport; Electron Transport Complex III; Hydroquinones; Intracellular Membranes; Mitochondria; Models, Molecular; Multienzyme Complexes; Oxidation-Reduction; Protein Conformation; Protons; Quinone Reductases; Ubiquinone

Topics: Antioxidants; Breast Neoplasms; Cell Proliferation; Female; Glioma; Humans; Hydroquinones; Organophosphorus Compounds; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Ubiquinone

ENOX (ECTO-NOX) proteins are growth-related cell surface proteins that catalyze both hydroquinone or NADH oxidation and protein disulfide-thiol interchange and exhibit both prion-like and time-keeping (clock) properties. The two enzymatic activities they catalyze alternate to generate a regular period of 24 min in length. Here we report the cloning, expression, and characterization of a human candidate constitutive ENOX (CNOX or ENOX1) protein. The gene encoding this 643 amino acid long protein is located on chromosome 13 (13q 14.11). Functional motifs previously identified by site-directed mutagenesis in a cancer-associated ENOX (tNOX or ENOX2) as adenine nucleotide or copper binding along with essential cysteines are present, but the drug-binding motif (EEMTE) sequence of ENOX2 is absent. The activities of the recombinant protein expressed in Escherichia coli were not affected by capsaicin, EGCg, and other ENOX2-inhibiting substances. The purified recombinant protein bound ca. 2 mol of copper/mol of protein. Bound copper was necessary for activity. H260 and H579 were required for copper binding as confirmed by site-directed mutagenesis, loss of copper-binding capacity, and resultant loss of enzymatic activity. Addition of melatonin phased the 24 min period such that the next complete period began exactly 24 min after the melatonin addition as appears to be characteristic of ENOX1 activities in general. Oxidative activity was exhibited with both NAD(P)H and reduced coenzyme Q as substrate. Concentrated solutions of the purified candidate ENOX1 protein irreversibly formed insoluble aggregates, devoid of enzymatic activity, resembling amyloid.

Topics: Binding Sites; Cloning, Molecular; Copper; Humans; Hydroquinones; Melatonin; NADH, NADPH Oxidoreductases; NADP; Protein Binding; Recombinant Proteins; Ubiquinone

One-electron reduction of the dioxygen molecule by the reduced form of mitochondrial ubiquinones (Q) of the NADH dehydrogenase (complex I) and mitochondrial cytochrome bc1 (complex III) is believed to be the main source of the superoxide anion radical O2*- and the hydroperoxide radical OOH*. In this work, we modeled the energetics of four possible reactions of the triplet ((3)Sigma(g)) dioxygen-molecule reduction by fully reduced and protonated ubiquinone (QH2; reaction 1), its deprotonated form (QH-; reaction 2), the semiquinone radical (QH*; reaction 3), and the semiquinone anion radical (Q*-; reaction 4), by means of ab initio calculations with the 6-31G(d) and 6-31+G(d) basis set in the restricted open-shell Hartree-Fock (ROHF), unrestricted Hartree-Fock (UHF), and complete active space self-consistent field (CASSCF) with dynamic correlation [at the second-order Møller-Plesset (MP2) or multiple reference Møller-Plesset (MRMP), respectively] schemes and the basis set superposition error (BSSE) correction included, as well as semiempirical AM1 and PM3 calculations in the UHF and ROHF schemes. 2-Butene-1,4-dione and p-benzoquinone were selected as model compounds. For the reduced forms of both compounds, reaction 1 turned out to be energetically unfavorable at all levels of theory, this agreeing with the experimentally observed diminished reductive properties of hydroquinone derivatives at low pH. For 2-butene-1,4-dione treated at the most advanced MRMP/CASSCF/6-31+G(d) level, the energies of reactions 1-4 are 4.7, -34.3, -15.0, and -4.1 kcal/mol, respectively. This finding suggests that reactions 2 and 3 are the most likely mechanisms of electron transfer to molecular oxygen in aprotic environments and that proton transfer is involved in this process. Nearly the same energies of reactions 2 and 3 were calculated at the MRMP/CASSCF/6-31+G(d) level for reduced forms of p-benzoquinone. Inclusion of diffuse functions in the basis set and dynamic correlation at the CASSCF level appears essential. Because deprotonated ubiquinol is unlikely to exist in physiological environments, reaction 3 appears to be the most likely mechanism of one-electron reduction of oxygen; however, if oxygen can penetrate cytochrome bc1 as far as the Q(o) center where ubiquinol can be deprotonated, reaction 2 can also come into play. The energies of reactions 2 and 3 calculated at the MRMP/CASSCF/6-31+G(d) level are most closely reproduced in the ab initio and semiempirical UHF PM3 c

Topics: Benzoquinones; Butanones; Hydroquinones; Mitochondria; Models, Chemical; Models, Molecular; Oxidation-Reduction; Oxygen; Protons; Thermodynamics; Ubiquinone

The involvement of coenzyme Q (CoQ) as an antioxidant agent in several oxidative processes both in vitro and in vivo is nowadays pointed out by several biochemical and clinical studies, but the chemical mechanisms of this action are not yet unequivocally established. Electrochemistry provides very useful techniques for the analysis of the kinetics and thermodynamics, and mechanisms of chemical phenomena involving electron transfers, e.g. in the case of radical reactions. In the present study we used cyclic voltammetry to investigate the interactions between oxygen radicals and ubiquinone in aprotic medium, a condition similar to that existing in the biological membranes. The results obtained showed that ubiquinone is more easily reduced than oxygen, ruling out the possibility of an electron transfer from semiquinone to oxygen to produce superoxide radicals. On the contrary, it was demonstrated that fully reduced quinone is able to scavenge the superoxide radical, by reduction to peroxide ion, lowering actually the oxidative potential in the medium.

Topics: Antioxidants; Coenzymes; Dimethylformamide; Electrochemistry; Electron Transport; Hydroquinones; Oxidation-Reduction; Peroxides; Reactive Oxygen Species; Solvents; Superoxides; Ubiquinone

Previously we reported that astroglial cells cultured from mouse brain synthesize and secrete nerve growth factor (NGF) and that, in quiescent cells, catecholamines markedly increase the NGF content in the conditioned medium (CM). We wished to further assess the structural properties required for exhibition of such effect of compounds containing a ring structure analogous to that of catechol on astroglial NGF synthesis. During our study, we found that hydroquinone, which was confirmed not to stimulate NGF synthesis in mouse fibroblast cells in another of our investigations, is a potent stimulator of NGF synthesis in astroglial cells and that 1,4-benzoquinone, an oxidized form of hydroquinone, is a more effective stimulator than hydroquinone itself. In addition, the results of experiments with 1,2-benzoquinone derivatives indicated that the presence of a long aliphatic side chain in the molecule eliminates the stimulatory effect of 1,4-benzoquinone on NGF synthesis in astroglial cells.

Topics: Animals; Astrocytes; Benzoquinones; Brain; Catechols; Cells, Cultured; Hydroquinones; Mice; Mice, Inbred ICR; Molecular Structure; Nerve Growth Factors; Quinones; Resorcinols; Structure-Activity Relationship; Ubiquinone

Topics: Hydroquinones; Liver; Mitochondria; Naphthoquinones; Oxidative Phosphorylation; Retinoids; Ubiquinone; Vitamin K