Detoxification of Reactive Oxygen Species

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Reactive oxygen species such as superoxide (O2.-), peroxides (ROOR), singlet oxygen, peroxynitrite (ONOO-), and hydroxyl radical (OH.) are generated by cellular processes such as respiration (reviewed in Murphy 2009, Brand 2010) and redox enzymes and are required for signaling yet they are damaging due to their high reactivity (reviewed in Imlay 2008, Buettner 2011, Kavdia 2011, Birben et al. 2012, Ray et al. 2012). Aerobic cells have defenses that detoxify reactive oxygen species by converting them to less reactive products. Superoxide dismutases convert superoxide to hydrogen peroxide and oxygen (reviewed in Fukai and Ushio-Fukai 2011). Catalase and peroxidases then convert hydrogen peroxide to water.
Humans contain 3 superoxide dismutases: SOD1 is located in the cytosol and mitochondrial intermembrane space, SOD2 is located in the mitochondrial matrix, and SOD3 is located in the extracellular region. Superoxide, a negative ion, is unable to easily cross membranes and tends to remain in the compartment where it was produced. Hydrogen peroxide, one of the products of superoxide dismutase, is able to diffuse across membranes and pass through aquaporin channels. In most cells the primary source of hydrogen peroxide is mitochondria and, once in the cytosol, hydrogen peroxide serves as a signaling molecule to regulate redox-sensitive proteins such as transcription factors, kinases, phosphatases, ion channels, and others (reviewed in Veal and Day 2011, Ray et al. 2012). Hydrogen peroxide is decomposed to water by catalase, decomposed to water plus oxidized thioredoxin by peroxiredoxins, and decomposed to water plus oxidized glutathione by glutathione peroxidases (Presnell et al. 2013).

Literature References
PubMed ID Title Journal Year
21453242 Superoxide dismutase in redox biology: the roles of superoxide and hydrogen peroxide

Buettner, GR

Anticancer Agents Med Chem 2011
22196163 Mathematical and computational models of oxidative and nitrosative stress

Kavdia, M

Crit Rev Biomed Eng 2011
21473702 Superoxide dismutases: role in redox signaling, vascular function, and diseases

Fukai, T, Ushio-Fukai, M

Antioxid. Redox Signal. 2011
23469953 Computational insights into the role of glutathione in oxidative stress

Presnell, CE, Bhatti, G, Numan, LS, Lerche, M, Alkhateeb, SK, Ghalib, M, Shammaa, M, Kavdia, M

Curr Neurovasc Res 2013
21375475 Hydrogen peroxide as a signaling molecule

Veal, E, Day, A

Antioxid. Redox Signal. 2011
19061483 How mitochondria produce reactive oxygen species

Murphy, MP

Biochem. J. 2009
22286106 Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling

Ray, PD, Huang, BW, Tsuji, Y

Cell. Signal. 2012
20064600 The sites and topology of mitochondrial superoxide production

Brand, MD

Exp. Gerontol. 2010
23268465 Oxidative stress and antioxidant defense

Birben, E, Sahiner, UM, Sackesen, C, Erzurum, S, Kalayci, O

World Allergy Organ J 2012
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