Oxidative Stress in Hyperhomocysteinemia

 

 

Autooxidation of homocysteine may produce hydrogen peroxide (H202). Indirect oxidative effects of hyperhomocysteinemia may include generation of superoxide from uncoupled endothelial nitric oxide synthase (eNOS), xanthine oxidase, or NAD(P)H oxidase, downregulation of antioxidant enzymes, and depletion of intracellular glutathione. In the presence of transition metals such as copper (Cu) or iron (Fe), H202 and superoxide (O2·-) may react to form hydroxyl radical (·OH).  Hydroxyl radical may promote the generation of lipid peroxyl radicals (LOO·), and both superoxide and lipid peroxyl radicals may react rapidly with endothelium-derived nitric oxide (·NO) to produce peroxynitrite (ONOO-) or lipid peroxynitrites (LOONO), respectively. SOD, superoxide dismutase; ONO-, nitrite.