Fig. 2

Simplified model outlining NOS dysfunction and modulation of ROS in PCOS- High concentrations of ADMA functions to competitively inhibit NOS at the L-Arg binding site, resulting in O₂^•− and free L-Arg accumulation. The accumulated L-Arg may be consumed under these conditions by arginase to give ornithine and urea. Other sources for O₂^•− are NADPH oxidase, xanthine reductase, mitochondrial damage, zinc deficiency, and high macrophage activity, which may be increased in PCOS. O₂^•− without sufficient NO will not produce ONOO⁻ resulting in low observed protein nitration. Accumulation of O₂^•− either slowly decays to H₂O₂ or in the presence of sufficient zinc is dismutased by SOD into H₂O₂. The low reported zinc concentrations and high copper in PCOS suggests low SOD activity. H₂O₂ then is converted to H₂O by catalase and/or reacts with free metals such as iron and copper through the Fenton reaction to generate the highly toxic ^•OH, resulting in lipid peroxidation events