Nitric oxide (NO) is synthesized from arginine by NO synthase (NOS), and the availability of
arginine is one of the rate-limiting factors in cellular NO production. Citrulline that is formed
as a by-product of the NOS reaction can be recycled to arginine by successive actions of
argininosuccinate synthetase (AS) and argininosuccinate lyase (AL), forming the citrulline-
NO cycle. AS and sometimes AL have been shown to be coinduced with inducible NOS
(iNOS) in various cell types including activated macrophages, microglia, vascular smooth …