FIGURE 11.

GPx3 converts hydrogen or lipid peroxides to their corresponding alcohols (i.e. water and lipid alcohols), inhibiting the cascade of platelet activation. ADMA inhibits NO synthase, which inhibits synthesis of NO (dotted line) from L-arginine. Platelet activation is greatest in an ADMA-rich, GPx3-deficient state consistent with the plasma environment of patients with severe CKD. In this environment, platelet inhibitory NO is decreased by reduced synthesis via ADMA inhibition of NO synthase and by increased oxidative consumption via reaction with peroxyl derivatives of hydrogen and lipid peroxides.