Methionine and Antioxidant Potential - Methionine and Antioxidant Potential - Open Access Pub

Methionine (Met) is a nutritionally essential amino acid and has been widely demonstrated to improve cellular oxidative balance and mediate oxidative stress. Met targets reactive oxygen species (ROS) directly by being oxidized to Met sulfoxide (MetO) 1. Met can be metabolized to cysteine (Cys) through transsulfuration pathway, which is further metabolized to glutathione (GSH), taurine, and hydrogen sulfide (H2S). All these metabolites exhibit antioxidant functions in various models (reviewed at 2). More recently, Met also has been demonstrated to enhance cellular oxidative tolerance via pentose phosphate pathway (PPP) 3, which contributes to the balance of cellular reducing power and accelerates the reduction reaction of MetO and GSH oxidative product GSSH back to Met and GSH. DOI 10.14302/issn.2471-2140.jaa-16-1378 Met Oxidation (Met Sulfoxide) Met, as a free amino acid or bound to a protein, is readily metabolized and interacts with various ROS, such as hydrogen peroxide (H2O2), hydroxyl radicals, hypochlorite, chloramines, and peroxynitrite 4. These oxidants oxidize Met residues into a mixture of the R- and S-isomers of MetO 5. Metabolome analysis reveals that dietary excess Met increases accumulation of Met oxidation products, such as MetO and Ac-Met sulfoxide (a MetO metabolite) 6. Previous report suggests that Met oxidation mainly protects critical residues at the active site against oxidative modification of proteins 1. For example, glutamine synthetase contains 16 Met residues, 8 surface exposed Met residues are oxidized with little effect on catalytic activity of the enzyme after exposure to H2O2, while the other intact residues are generally buried within the core of the protein and guard the entrance to the active site 7. However, the recent experimental models suggested that Met oxidation involves in activation or inactivation of protein function and is now established as a novel mode of redox-regulation of protein function similar with thiol-based redox-regulation of protein function 8. For example, calcium/calmodulin (Ca2+/CaM)-dependent protein kinase II is a prototypical methionine redox sensor and oxidation of paired regulatory domain Met residues enhances its activity by pro-oxidant conditions 1,9, while oxidative stress-induced Met residues oxidation leads to the accumulation of chemically and functionally altered alpha-synuclein with reducing its affinity for biological membranes and impairing degradation the by 20S proteasome 10. Met oxidation can be reversed by NADPH-dependent MetO reductases (Msr), which have been identified in