Coenzyme Q(10)--its role as a prooxidant in the formation of superoxide anion/hydrogen peroxide and the regulation of the metabolome.
Coenzyme Q10 plays a central role in cellular bioenergy generation and its regulation. Closed membrane systems generate a proton motive force to create transient localized bio-capacitors; the captured energy is used for the synthesis of mitochondrial ATP but also for many other processes, such as metabolite translocations, nerve conduction and a host of other bioenergy requiring processes. Coenzyme Q10 plays a key role in many of these sub-cellular membrane energy generating systems. Integral to this phenomenon is the prooxidant role of coenzyme Q10 in generating the major superoxide anion/hydrogen peroxide second messenger system. This messenger system, largely but not exclusively, arises from coenzyme Q10 semiquinone function; it contributes to the regulation of sub-cellular redox potential levels; transcription/gene expression control; is essential for modulated protein turnover and activation; mediates hormone and growth factor extracellular signaling. The regulated prooxidant formation of the superoxide anion/H2O2 second messenger system is essential for the normal physiological function of the metabolome. The normally functioning metabolome is the expression of a finely tuned dynamic equilibrium comprised of thousands of anabolic and catabolic reactions and all cellular signaling systems must be finely regulated. There is still much to be learnt about the up/down regulation of the H2O2 messenger system. The concept that superoxide anion/H2O2 cause random macromolecular damage is rebutted. The administration of antioxidants to quench the inferred toxicity of these compounds as a therapy for age associated diseases is unsupported by extant mammalian clinical trials and should be subject to serious re-evaluation. The role of ascorbic acid as a beneficial hydrogen peroxide prodrug is discussed.
Linnane
Anthony W
AW
Centre for Molecular Biology and Medicine, Epworth Medical Centre, 185-187 Hoddle Street, Richmond, Melbourne, Vic. 3121, Australia. tlinnane@cmbm.com.au
Kios
Michael
M
Vitetta
Luis
L
D000818:Animals; D000838:Anions; D000975:Antioxidants / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003067:Coenzymes / Q000737:chemistry / Q000502:physiology; D004272:DNA, Mitochondrial / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D016877:Oxidants / Q000378:metabolism*; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000502:physiology
D000838:Anions; D000975:Antioxidants; D003067:Coenzymes; D004272:DNA, Mitochondrial; D016877:Oxidants; D013481:Superoxides; D014451:Ubiquinone; D006861:Hydrogen Peroxide; C024989:coenzyme Q10