Nitric oxide (NO) has been recently shown to be an endogenous molecule of significant biological importance. It has been shown to play a role in, among other things, the activation of guanylate cyclase and in the cytotoxicity associated with activated macrophages. Thus, the biological significance of NO makes the elucidation of the biosynthetic pathway exceedingly important. For example, inadequate NO biosynthesis can possibly contribute to hypertension, atherosclerosis, male impotence, or immune system deficiency. The research described in this proposal intends to elucidate the mechanism of NO generation from the endogenous precursor, arginine. By utilizing synthetic arginine analogs, the mechanism of oxidation, the binding specificity and the general enzymology will be investigated. As the significance of NO in physiology grows, there will be an increased need for specific and potent compounds to be used to demonstrate NO function. This approach will allow the development of a series of compounds which will be valuable research tools. Also, the knowledge gained from this approach will provide a basis for the development of compounds of potential therapeutic utility.
