Nitration of γ-tocopherol and oxidation of α-tocopherol by copper-zinc superoxide dismutase/H2O2/NO2-: Role of nitrogen dioxide free radical

Ravinder J. Singh, Steven P.A. Goss, Joy Joseph, B. Kalyanaraman

Research output: Contribution to journalArticlepeer-review

76 Scopus citations


Copper-zinc Superoxide dismutase (Cu,Zn-SOD) is the antioxidant enzyme that catalyzes the dismutation of Superoxide (O2.-) to O2 and H2O2. In addition, Cu,ZnSOD also exhibits peroxidase activity in the presence of H2O2, leading to self-inactivation and formation of a potent enzyme-bound oxidant. We report in this study that lipid peroxidation of L-α-lecithin liposomes was enhanced greatly during the SOD/H2O2 reaction in the presence of nitrite anion (NO2-) with or without the metal ion chelator, diethylenetriaminepentacetic acid. The presence of NO2- also greatly enhanced α-tocopherol (α-TH) oxidation by SOD/H2O2 in saturated 1,2-dilauroyl-sn-glycero-3-phosphatidylcholine liposomes. The major product identified by HPLC and UV-studies was α-tocopheryl quinone. When 1,2-diauroyl-sn-glycero-3-phosphatidylcholine liposomes containing γ-tocopherol (γ-TH) were incubated with SOD/H2O2/NO2-, the major product identified was 5-NO2-γ-TH. Nitrone spin traps significantly inhibited the formation of α-tocopheryl quinone and 5-NO2-γ-TH. NO2- inhibited H2O2-dependent inactivation of SOD. A proposed mechanism of this protection involves the oxidation of NO2- by an SOD-bound oxidant to the nitrogen dioxide radical (.NO2). In this study, we have shown a new mechanism of nitration catalyzed by the peroxidase activity of SOD. We conclude that NO2- is a suitable probe for investigating the peroxidase activity of familial Amyotrophic Lateral Sclerosis-linked SOD mutants.

Original languageEnglish (US)
Pages (from-to)12912-12917
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number22
StatePublished - Oct 27 1998

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Nitration of γ-tocopherol and oxidation of α-tocopherol by copper-zinc superoxide dismutase/H<sub>2</sub>O<sub>2</sub>/NO<sub>2</sub><sup>-</sup>: Role of nitrogen dioxide free radical'. Together they form a unique fingerprint.

Cite this