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Tuesday, May 31, 2011

Reactive Oxygen Species (ROS) Oxidative Stress & Antioxidants

In the mitochondrial respiratory chain, oxygen is "partially reduced" to form superoxide. Superoxide is a radical, i.e. a chemical species with an unpaired electron. Radicals usually are very reactive species, because electrons like to pair up to form stable two-electron bonds. Because of its radical character, superoxide is also called a "Reactive Oxygen Species" (ROS). ROS form as a natural byproduct of the normal metabolism of oxygen and have important roles in cell signaling and homeostasis. However, during times of environmental stress (e.g., UV or heat exposure), ROS levels can increase dramatically. This may result in significant damage to cell structures. This cumulates into a situation known as oxidative stress. ROS are also generated by exogenous sources such as ionizing radiation.

Oxidative Stress

Oxidative stress is imposed on cells as a result of one of three factors:

  1. an increase in oxidant generation,

  2. a decrease in antioxidant protection, or

  3. a failure to repair oxidative damage.

Cell damage is induced by reactive oxygen species (ROS). ROS are either free radicals, reactive anions containing oxygen atoms, or molecules containing oxygen atoms that can either produce free radicals or are chemically activated by them. Examples are hydroxyl radical, superoxide, hydrogen peroxide, and peroxynitrite. The main source of ROS in vivo is aerobic respiration, although ROS are also produced by peroxisomal b-oxidation of fatty acids, microsomal cytochrome P450 metabolism of xenobiotic compounds, stimulation of phagocytosis by pathogens or lipopolysaccharides, arginine metabolism, and tissue specific enzymes. Under normal conditions, ROS are cleared from the cell by the action of superoxide dismutase (SOD), catalase, or glutathione (GSH) peroxidase. The main damage to cells results from the ROS-induced alteration of macromolecules such as polyunsaturated fatty acids in membrane lipids, essential proteins, and DNA. Additionally, oxidative stress and ROS have been implicated in disease states, such as Alzheimer's disease, Parkinson's disease, cancer, and aging.

Antioxidants

Antioxidants are scavengers of Reactive oxygen species (ROS), Antioxidants scavenge ROS before they cause damage to the various biological molecules, or prevent oxidative damage from spreading, e.g. by interrupting the radical chain reaction of lipid peroxidation. The antioxidant defense systems in the human body are extensive and consist of multiple layers, which protect at different sites and against different types of ROS.some of the enzymes which acts in clearing ROS are superoxide dismutase (SOD), catalase, or glutathione (GSH) peroxidase.

we are constantly exposed to ROS generated from endogenous and some exogenous sources. These ROS react with biological molecules, such as DNA, proteins, and lipids, causing structural and functional damage. Oxidative damage accumulates in human tissues with age and can causally contribute to a number of degenerative diseases, such as heart disease and cancer. Antioxidants, both enzymatic and non-enzymatic, limit oxidative damage to biological molecules by various mechanisms. Dietary antioxidants, such as vitamins C and E, significantly contribute to antioxidant defense systems in humans and may help protect us from certain age-related degenerative diseases.

References:

Fiers, W., et al., More than one way to die: apoptosis, necrosis and reactive oxygen damage Oncogene., 18, 7719-7730 (1999).

Nicholls, D.G., and Budd, S.L., Mitochondria and neuronal survival. Physiol. Rev., 80, 315-360 (2000).

Hayes, J.D., et al., Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defense against oxidative stress. Free Radic. Res., 31, 273-300 (1999).

http://lpi.oregonstate.edu/f-w97/reactive.html

http://www.sigmaaldrich.com/life-science/cell-biology/learning-center/pathway-slides-and/oxidative-stress.html

en.wikipedia.org/wiki/Reactive_oxygen_species