Electron Spin Resonance Investigation of the Thiyl Free Radical Metabolites of Cysteine, Glutathione, and Drugs

Abstract

Most biochemicals, as opposed to aromatic drugs and industrial chemicals, are not easily metabolized through free radical intermediates. Cysteine and glutathione (GSH) are among the rather rare exceptions to this rule. The sulfhydryl group of L-cysteine plays many important roles in both the structure and function of proteins. These roles are modulated by the oxidation of L-cysteine. The ease of L-cysteine oxidation is also responsible for the radioprotection of intracellular GSH,¹ the bactericidal effect of cysteine,² and the general toxicity of cysteine. For this reason, N-acetylcysteine, and not cysteine, is used to treat the cases of acetaminophen (paracetamol) overdose.³ The oxidation of thiol compounds, including Lcysteine, by ionizing radiation has been studied for a number of years. Sulhydryl compounds have been used to try to prevent radiation damage to normal tissue during radiation therapy. In fact, the high concentration of GSH in tissues provides significant radiation protection naturally. Among the stable products of oxidation of L-cysteine are L-cystine, L-cysteine sulfinic acid and L-cysteine sulfonic acid. These diamagnetic products of oxidation by metal ions or irradiation form via free radical intermediates, with the L-cysteine thiyl radical either dimerizing to form L-cystine,

$$RSH\xrightarrow{-{{H}^{\centerdot }}}R{{S}^{\centerdot }}\to 1/2RSSR$$

or reacting with molecular oxygen or hydrogen peroxide to form the oxygen-containing products.