Nitric Oxide: Biological Targets
Nitric oxide (NO) is an essential signaling molecule for many eukaryotic organisms. NO is produced in vivo by the enzyme nitric oxide synthase (NOS) from the amino acid L-arginine. The apolar gas readily diffuses across cell membranes, where it binds to the heme of soluble guanylate cyclase (sGC), the principle NO receptor. Once activated, sGC converts GTP to cGMP at a rate that is several-hundred-fold above the basal level. This NO/cGMP signaling cascade modulates several physiologic processes including vasodilation, platelet aggregation, and neurotransmission. Although the cGMP-dependent affects of NO remain active areas of research, additional cGMP-independent responses to NO also are being investigated. Endogenous levels of NO can modulate protein function by S-nitrosation, a covalent modification that has been implicated in the transcriptional regulation of genes involved in the immune response and in apoptosis.
