Glutathione: mechanism and kinetics of its non-enzymatic defense action against free radicals

Abstract

Glutathione, which is the most abundant cytosolic thiol, plays important roles in the non-enzymatic antioxidant defence system. Its free radical scavenging activity towards radicals of different nature (·OH, ·OOH, ·OCH₃, ·OOCH₃, ·OOCHCH₂ and ·OOCCl₃) have been studied in aqueous solution, using the Density Functional Theory. It was found that the rate constants range from 2.02 × 10⁴ M⁻¹s⁻¹ to diffusion limit (7.68 × 10⁹ M⁻¹s⁻¹). Therefore it can be stated that glutathione is an excellent free radical scavenger, able of efficiently scavenging a wide variety of free radicals. It reacts exclusively by H transfer, and with the exception of its reaction with ·OH there is only one important channel of reaction, yielding to the S-centered radical. For the reaction with ·OH, on the other hand, a wide product distribution is expected, which explains the formation of C-centered radicals experimentally observed. Glutathione was found to be exceptionally good as a OOH radical scavenger, comparable to 2-propenesulfenic acid. This has been explained based on the strong H bonding interactions found in the transition states, which involves the carboxylate moiety. Therefore this might have implications for other biological systems where this group is present.