2428 caveolae (García-Cardeña et al., 1996; Liu et al., 1995; Liu et al., 1997; Liu and Sessa, 1994). Similar to nNOS and iNOS, eNOS contains a C-terminal reductase domain, which binds NADPH, and transfers electrons from NADPH to FAD to FMN, and ultimately to the N-terminal oxygenase domain, which contains a heme, and binding sites for arginine, tetrahydrobiopterin and CaM. eNOS utilizes molecular oxygen and electrons from NADPH to oxidize the substrate L-arginine into the intermediate OH-L-arginine, which is then oxidized into NO and L-citrulline (Griffith and Stuehr, 1995). Two autoinhibitory control elements (ACE-I and ACE-II) impede eNOS activation and influence the calcium/CaM sensitivity of the enzyme (Lane and Gross, 2002; Salerno et al., 1997). Given the localization of T497, S617 and S635 in ACE-1 and S1179 in ACE-II, it is likely that phosphorylation removes the steric hindrance imparted by these non-catalytic inserts and permits better fidelity of electron flux from the reductase domain to NO generation in the oxygenase domain (McCabe et al., 2000).