Nitric oxide synthase: models and mechanisms

The overproduction or underproduction of nitric oxide has been implicated i n pathological symptoms such as endotoxic shock, diabetes, allograft reject ion, and myocardial ischimia/reperfusion injury. A thorough understanding o f the biosynthesis of nitric oxide is necessary to probe and manipulate the se signaling events. There is also considerable pharmacological interest in developing selective inhibitors of the several isoforms of nitric oxide sy nthase. The recently determined crystal structures of complexes between nit ric oxide synthase and substrate, the mechanisms of the enzymatic reaction that generate nitric oxide and chemical precedents and models for these rea ctions are now coming into focus, but there are still numerous fascinating and unanswered questions regarding nitric oxide biosynthesis.