NO is a free radical generated by NOS (NO synthase) in a two-step five-electron oxidation of the terminal guanidino nitrogen of L-arginine.
ADMA competitively inhibits the production of NO by NOS and additionally, along with symmetrical dimethylarginine (SDMA) and L-lysine, competes with L-arginine for transport across the cell membrane [8].
It is known that arginine is converted to NO by NOS, as depicted in Figure 1a.
The pathophysiology of asthma may be determined by a delicate balancing of the production of NO by NOS isoforms.
Because oxygen is necessary for NO production by NOS, alveolar hypoxia will result in a reduced activity of NOS [ 11].
NO generated by NOS reacts with intracellular glutathione to form nitrosoglutathione, an intracellular reservoir, which in turn transnitrosylate protein thiol to form nitrocysteine, thus modifying protein functions [19].
Furthermore, GTP cyclohydrolase, the rate-limiting enzyme for BH4 (tetrahydrobiopterin) synthesis, has been shown to regulate pain sensitivity and persistence in the periphery via BH4, an essential cofactor for NO production by NOS [19].
Therefore, l-Arg was probably not limiting for NO production by NOS in this setting.
Agmatine is decarboxylated arginine, and thus agmatine biosynthesis competes with nitrogen metabolism by arginase and NO synthesis by NOS.
NO plays an essential signaling role in mammalian neurotransmission, vasodilation, and immune response and therefore misregulation of NO production by NOS is implicated in many disease states.
In many cell types, increases in cGMP levels are due to the activation of soluble guanylate cyclase (GC) after NO generation by NOS.
