Understanding the effect of osmolytes on antioxidant enzymes Thermodynamic structural and functional aspects

Abstract

newline Normal physiological reactions in our body along with prolonged exposure to the environmental stresses and high dietary xenobiotics result in generation of free radicals. An excess accumulation of these free radicals, beyond a physiological level, induces oxidative stress which is detrimental for the cellular macromolecules. Among these macromolecules, proteins are particularly vulnerable to oxidative stress with a ~69% of the oxidized molecules being proteins and the remaining 31% constitutes for lipids and nucleic acids. With respect to the effect of free radicals on proteins, the free radical oxidized proteins have been shown to exhibit a compromised structure, stability and function. One of the principal defense systems to overcome the oxidative stress includes antioxidant enzymes, including catalase and superoxide dismutase, that respectively neutralize the highly detrimental superoxide (O2-.) and hydrogen peroxide (H2O2). In fact, they work in a coordinated and sequential manner to carry out this detoxification process. H2O2, accumulated as a result of SOD catalyzed dismutation of O2-., acts as a substrate for catalase, that further breaks it down to avoid its undesirable effects on cells. Although being a highly regulated and an efficient process, the neutralization of oxidative stress in certain conditions puts the antioxidant enzymes themselves, although being resistant, under high risk to the free radical induced oxidative damage. Generally during oxidative stress conditions, an increased expression with increased activity of these enzymes has been reported under both in vivo and in vitro conditions. For this, antioxidant enzymes need to maintain the delicate equilibrium between their functional flexibility and structural rigidity for performing their function effectively. However, in several oxidative stress related disorders like Alzheimer s, Parkinson s, diabetes, renal dysfunction and Familial amyotrophic lateral sclerosis, an enhanced expression with reduced activity of these antioxid