| [ Summary ] |
Hyperhomocysteinemia, which has been shown to be a risk factor for arteriosclerosis, occurs frequently in end-stage renal disease. Since the SH group of Hcy is simultaneously autooxidized with other SH groups, Hcy cytotoxicity might be attributed to the generation of O2-- and H2O2, which has direct toxic effects on endothelial cells and accelerates platelet aggregation. In the presence of NO, thiols containing the SH group form RSNOs (S-nitrosothiols). RSNOs stabilize the SH group of Hcy and prevent its autooxidation. As Hcy is accumulated and NO synthesis is depressed in the uremic state, RSNO formation is disturbed. Instead, ONOO-, which is more toxic than O2-- and H2O2, may be formed from NO and O2--. Therefore, hyperhomocysteinemia might cause endothelial dysfunction and arteriosclerosis in a uremic state. On the other hand, NO might cause hyperhomocysteinemia, since NO inhibits methionine synthase that catalyzes the remethylation step from Hcy to Met. |