Regulation of nitric oxide generation and consumption

Nitric oxide (NO), originally discovered for its role in cardiovascular function, is a key molecule in physiological processes including metabolism, neurotransmission (including memory, learning, neuroprotection and synaptic plasticity), immunity, reproduction, and much more. NO can be synthesized by the catalytic activity of the enzyme nitric oxide synthase (NOS), which is found biologically in three isoforms, or nonenzymatically based on simple reduction of nitrate and nitrite or by the NO-donor S-nitrosothiol (R-SNO). Importantly, the deficiency of NO has been noted in a wide range of pathologies including cardiovascular disease, cancer, erectile dysfunction, male and female infertility, and mitochondrial disease. While there are several pathways that can lead to a reduction in the bioavailability of NO (i.e., consumption, inhibition, and substrate competition) it is the conclusion of the authors that multiple pathways co-exist in pathological states. This article outlines for the first time the major pathways of NO generation, the importance of NO in health, NO scavenging and enzyme inhibition, and the potential benefits of supplementation.