Free-radical scavenging by tryptophan and its metabolites through electron transfer based processes

Abstract

Free-radical scavenging by tryptophan and eight of its metabolites through electron transfer was investigated in aqueous solution at physiological pH, using density functional theory and the Marcus theory. A test set of 30 free radicals was employed. Thermochemical and kinetic data on the corresponding reactions are provided here for the first time. Two different pathways were found to be the most important: sequential proton loss electron transfer (SPLET) and sequential double proton loss electron transfer (SdPLET). Based on kinetic analyses, it is predicted that the tryptophan metabolites kynurenic acid and xanthurenic acid are the best free-radical scavengers among the tested compounds; they were estimated to be at least 24 and 12 times more efficient than Trolox for scavenging (•)OOH. These findings are in line with previous reports suggesting that the antioxidant activity that has been attributed to tryptophan is actually due to its metabolites, and they demonstrate the particular importance of phenolic metabolites to such activity. Graphical Abstract Kynurenic acid (KNA) and xanthurenic acid (XNA) are the major contributors to the free-radical scavenging activity of tryptophan.

Physiological roles of tryptophan in teleosts: current knowledge and perspectives for future studies

“…In the same way, other studies about tryptophan metabolites, such as 5-hydroxytryptophan, indole-3-acetic acid, 3-hydroxyanthranilic acid, 3-hydroxykynurenine or xanthurenic acid, have demonstrated their antioxidant capacities both as ROS scavengers and modulation of antioxidant enzymes (Christen et al 1990;Matuszak et al 1997;Peyrot & Ducrocq 2008;Ferrari et al 2014;P erez-Gonz alez et al 2015). Similarly, some tryptophan-metabolizing enzymes, such as tryptophan 2,3-dioxygenase (TDO; EC 1.13.11.11) and indoleamine 2,3-dioxygenase (IDO; EC 1.13.11.52), have been considered as antioxidant since in their reactions to catalyse the oxidative degradation of tryptophan, they use the superoxide anion and hydrogen peroxide as cofactors (Hayaishi 1996;Britan et al 2006;Batabyal & Yeh 2007).…”

“…; Pérez‐González et al . ). Similarly, some tryptophan‐metabolizing enzymes, such as tryptophan 2,3‐dioxygenase (TDO; EC 1.13.11.11) and indoleamine 2,3‐dioxygenase (IDO; EC 1.13.11.52), have been considered as antioxidant since in their reactions to catalyse the oxidative degradation of tryptophan, they use the superoxide anion and hydrogen peroxide as cofactors (Hayaishi ; Britan et al .…”

Carboxyl Group as a Radical Scavenging Moiety: Thermodynamics of 2H+/2e– Processes of Phloretic Acid

“…It should be noted that small positive values of rG o (<10 kcal/mol) do not necessarily mean that the corresponding radical scavenging reactions should be neglected. [51] Such processes may represent notable reaction pathways if they take place at significant rates. On the other hand, it is expected that products yielded via significantly endergonic reaction pathways will not be experimentally detectable, even if they may occur at a significant rate.…”

Endotoxin-Induced Tryptophan Degradation along the Kynurenine Pathway: The Role of Indolamine 2,3-Dioxygenase and Aryl Hydrocarbon Receptor-Mediated Immunosuppressive Effects in Endotoxin Tolerance and Cancer and Its Implications for Immunoparalysis

“…Increased concentrations of KYNA and xanthurenic acid (3-Hydroxy KYNA, XA) were detected in the plasma of patients with type 2 diabetes, presumably due to chronic stress or the low-grade inflammation that are prominent risk factors for diabetes [ 19 ]. Thermochemical and kinetic data show that KYNA and XA are the best free-radical scavengers from the eight tested TRP metabolites [ 20 ], suggesting that the production is a regulatory mechanism to attenuate damage by the inflammation-induced production of reactive oxygen species. AA and 3-HA can act as antioxidants in certain chemical environments but, in the presence of iron(II), 3-HA exhibits prooxidant activity [ 21 ].…”