Natural Product Nitric Oxide Chemistry: New Activity of Old Medicines
A schematic presentation of a mammalian nitric oxide (NO) cycle. NO is generated by nitric oxide synthases (NOS) in most cells of the body and participates in regulation of numerous physiologic functions. The bioactivity of nitric oxide is partly regulated by its rapid oxidation to nitrite () or, in the presence of oxyhemoglobin, to nitrate (). Nitrate is the predominant nitric oxide oxidation product in the circulation. In our bodies, nitrate can undergo reduction to nitrite, and this process is strongly dependent on oral commensal bacteria. In blood and tissues, nitrite can be further reduced to nitric oxide and other bioactive nitrogen oxides. There are several enzymatic and nonenzymatic routes that can catalyze this reduction, most of which are greatly enhanced under hypoxic conditions. This mammalian nitrogen cycle can be fueled by the diet because vegetables contain high amounts of inorganic nitrate.