Peroxynitrite-derived carbonate and nitrogen dioxide radicals readily react with lipoic and dihydrolipoic acid. Free Radic Biol Med 2005 Jul 15;39(2):279-88
Date
06/21/2005Pubmed ID
15964519DOI
10.1016/j.freeradbiomed.2005.03.014Scopus ID
2-s2.0-20444456654 (requires institutional sign-in at Scopus site) 46 CitationsAbstract
Alpha-lipoic acid (LA) and dihydrolipoic acid (DHLA) may have a role as antioxidants against nitric oxide-derived oxidants. We previously reported that peroxynitrite reacts with LA and DHLA with second-order rate constants of 1400 and 500 M(-1) s(-1), respectively, but indicated that these direct reactions are not fast enough to protect against peroxynitrite-mediated damage in vivo. Moreover, the mechanism of the reaction of peroxynitrite with LA has been recently challenged (J. Biol. Chem.279:9693-9697; 2004). Pulse radiolysis studies indicate that LA and DHLA react with peroxynitrite-derived nitrogen dioxide (*NO2) (k2 = 1.3 x 10(6) and 2.9 x 10(7) M(-1) s(-1), respectively) and carbonate radicals (CO(3-)) (k2 = 1.6 x 10(9) and 1.7 x 10(8) M(-1) s(-1), respectively). Carbonate radical-mediated oxidation of LA led to the formation of the potent one-electron oxidant LA radical cation. LA inhibited peroxynitrite-mediated nitration of tyrosine and of a hydrophobic tyrosine analog, N-t-BOC L-tyrosine tert-butyl ester (BTBE), incorporated into liposomes but enhanced tyrosine dimerization. Moreover, while LA competitively inhibited the direct oxidation of glutathione by peroxynitrite, it was poorly effective against the radical-mediated thiol oxidation. The mechanisms of reaction defined herein allow to rationalize the biochemistry of peroxynitrite based on direct and free radical-mediated processes and contribute to the understanding of the antioxidant actions of LA and DHLA.
Author List
Trujillo M, Folkes L, Bartesaghi S, Kalyanaraman B, Wardman P, Radi RAuthor
Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AntioxidantsCarbonates
Chromatography, High Pressure Liquid
Computer Simulation
Dimerization
Dose-Response Relationship, Drug
Free Radicals
Kinetics
Liposomes
Nitric Oxide
Nitrogen Dioxide
Oxygen
Peroxynitrous Acid
Sulfhydryl Compounds
Temperature
Thioctic Acid
Tyrosine