Richard Graham Knowles
Aug 1, 1996
Citations
8
Influential Citations
284
Citations
Quality indicators
Journal
Biochemical Society transactions
Abstract
Nitric oxide is a reactive free radical gas that can act as an intracellular or extracellular messenger. It may act locally as an autacoid, paracrine substance or neurotransmitter, and at a distant target if it is carried and delivered as a protected complex, or prodrug. It is therefore, a very unique signaling molecule. It is formed from L-arginine by a family of isoforms of nitric oxide synthases (NOS 1-3). These enzymes are separate gene products encoded on three different chromosomes. The three isoforms have about 50-60% homology and each isoform has considerable homology between species (about 90%). A variety of co-translational and posttranslational modifications of the different isoforms can take place, including phosphorylation, myristoylation and palmitoylation, each of which may influence their subcellular location and/or activity. This family of enzymes has considerable homology with cytochrome P450 and has both oxidase and reductase domains with complex cosubstrate and cofactor requirements that include heme, O2, NADPH, FAD, FMN, tetrahydrobiopterin and calmodulin. The enzyme isoforms are active as homodimers and catalyze the oxidation of the guanidino nitrogen of L-arginine to nitric oxide. The other product of the reaction is citrulline.