STRUCTURE AND FUNCTION OF NITRIC-OXIDE SYNTHASES

Nitric oxide (NO), which accounts for the biological activity of endot helium-derived relaxing factor, is now thought to play a variety of ro les in the nervous system and in immunologic reactions. NO is synthesi zed from L-arginine by nitric oxide synthase (NOS). There are three is oforms of NOS; type I (neuronal), type II (inducible), and type III (e ndothelial). The fundamental structure of the three isoforms, which co ntain calmodulin-, FMN-, FAD-, and NADPH-binding domains, is the same. Calmodulin is already bound to inducible NOS without requiring Ca2+, while the others are Ca2+/calmodulin-dependent. Endothelial NOS is bou nd to membranes by N-myristoylation, while the other isoforms are solu ble. The human endothelial NOS gene has been cloned. It has several hi ghly repetitive regions which could provide potential sites for DNA po lymorphism. It might be of interest to examine the relationship betwee n such polymorphism and cardiovascular disorders.