Lecture Note on Biochemistry for Medical Students:
SYNTHESIS AND REGULATION OF NITRIC OXIDE
Andrew Johan*)
SUMMARY
Nitric Oxide (NO) is produced in higher organisms by the oxidation of one of the terminal guanido-nitrogen atoms of L-arginine. Nitric Oxide Synthase (NOS) catalyzes the oxidation of arginine to NO and citrulline. Reduced nicotinamide adenine dinucleotide phosphate (NADPH) and oxygen (O2) are required as co-substrates.
NOS exists in three distinct isoforms: 1. constitutive neuronal NOS (NOS I or nNOS), 2. inducible NOS (NOS II or iNOS), and 3. constitutive endothelial NOS (NOS III or eNOS). The three NOS isoforms can be regulated by various stimuli. iNOS isoform is regulated at a pretranslational level and can be induced by proinflammatory cytokines, such as tumor necrosis factor a (TNFa), gamma interferon (IFNg), and interleukin (IL)1b. nNOS regulation are correlated with the response of neuronal cells to stress induced by physical, chemical, and biological agents such as heat, electrical stimulation, light exposure, and allergic substances. eNOS activity are correlated with the increase in intracellular Ca2+ concentration.
Nitric oxide is an important mediator of homeostatic processes and host defense mechanisms. Changes in its generation or actions contribute to pathologic states. How changes in the concentration of L-arginine influence the initiation, development, and resolution of some of these pathologic conditions remains to be elucidated. It seems that increased ingestion of L-arginine reverses the changes in host defense mechanisms, vascular reactivity and may also reduce blood pressure .