Modeling the activity of glutathione as a hydroxyl radical scavenger considering its neutral non-zwitterionic form
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ORIGINAL PAPER
Modeling the activity of glutathione as a hydroxyl radical scavenger considering its neutral non-zwitterionic form Amarjeet Yadav & Phool C. Mishra
Received: 10 May 2012 / Accepted: 20 September 2012 / Published online: 10 October 2012 # Springer-Verlag Berlin Heidelberg 2012
Abstract Glutathione is an immensely important antioxidant, particularly in the central nervous system. The scavenging mechanism of glutathione towards the OH radical was studied theoretically, considering its neutral, nonzwitterionic form relevant to acidic media. Gibbs free barrier and released energies involved in hydrogen abstraction from the different sites of glutathione by an OH radical were studied at the B3LYP/6-31G(d,p), B3LYP/AUG-cc-pVDZ, M06/AUG-cc-pVDZ, M06-2X/AUG-cc-pVDZ levels of density functional theory. Solvation in bulk aqueous media was also studied at all these levels of theory employing the polarizable continuum model. Our study shows that a hydroxyl radical can abstract a hydrogen atom easily from glutathione. Thus, glutathione is shown to be an efficient scavenger of OH radicals, which is in agreement with the results of previous studies. Keywords Glutathione . Hydroxyl radical . DFT
Introduction Glutathione is a tripeptide chain (γ-L-glutamyl-L-cysteinylglycine, GSH) made up of glutamic acid, cysteine and glycine [1, 2]. It is an immensely important antioxidant in the central nervous system and plays vital roles in cell metabolism [1–9]. Certain free radicals known as reactive oxygen species (ROS) and reactive nitrogen oxide species (RNOS) cause oxidative Electronic supplementary material The online version of this article (doi:10.1007/s00894-012-1601-2) contains supplementary material, which is available to authorized users. A. Yadav : P. C. Mishra (*) Department of Physics, Banaras Hindu University, Varanasi 221 005, India e-mail: [email protected]
and nitrative damage to DNA that leads to mutation and several diseases including cancer [10–12]. Glutathione scavenges ROS and RNOS, including the hydroxyl radical, efficiently from biological media [6–8]. Deficiency of glutathione in cellular environments leads to neurological disorders such as Parkinson’s disease, Alzheimer’s disease, schizophrenia, autism, etc. [4, 9]. Common anti-oxidants that occur in biological systems or can be obtained from external sources include βcarotene, ascorbic acid (vitamin C), N-acetylcysteine (NAC, a glutathione precursor), α-tocopherol (vitamin E), urocanic acid, uric acid, curcumin, etc. [13–17]. These agents protect biological systems from free radicals by transforming them into non-damaging forms while they themselves are modified [13–17]. In such a reaction, two glutathione molecules are converted to glutathione disulfide [18–21] from which glutathione can be regenerated by a nicotinamide adenine dinucleotide dependent reaction [18–26]. The structure of glutathione in aqueous solution and solid state has been studied experimentally [27–31]. At physiological pH, glutathione exists in an anionic form—the glycine
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