Nitric Oxide Synthases and Their Inhibitors: A Review

Abstract

Nitric Oxide (NO), an important biological mediator, is involved in the regulation of the cardiovascular, nervous and immune systems in mammals. Synthesis of NO is catalyzed by its biosynthetic enzyme, Nitric Oxide Synthase (NOS). There are three main isoforms of the enzyme, neuronal NOS, endothelial NOS and inducible NOS, which have very similar structures but differ in their expression and activities. NO is produced in the active site of the enzyme in two distinct cycles from oxidation of the substrate L-arg (L-arginine) in nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reaction. NOS has gained considerable attention of biochemists due to its complexity and unique catalytic mechanism. The review focuses on NOS structure, its function and catalytic reaction mechanism. In particular, the review is concluded with a discussion on the role of all three isoforms of NOS in physiological and pathological conditions and their inhibitors with a focus on the role of computational techniques in their development.