Nitric oxide. Novel biology with clinical relevance.
OBJECTIVE
The author provides the reader with a view of the regulation and function of nitric oxide (NO), based on the three distinct enzyme isoforms that synthesize NO.


BACKGROUND
Nitric oxide is a short-lived molecule exhibiting functions as diverse as neurotransmission and microbial killing. Recent advances in the characterization of the enzymes responsible for NO synthesis and in the understanding of how NO interacts with targets have led to new insights into the many facets of this diverse molecule.


METHODS
Nitric oxide is produced by one of three enzyme isoforms of NO synthesis. These enzymes vary considerably in their distribution, regulation, and function. Accordingly, the NO synthesis or lack of NO production will have consequences unique to that isoform. Therefore, this review summarizes the regulation and function of NO generated by each of the three isoforms.


RESULTS
Nitric oxide exhibits many unique characteristics that allow this molecule to perform so many functions. The amount, duration, and location of the NO synthesis will depend on the isoform of NO synthase expressed. For each isoform, there probably are disease processes in which deficiency states exist. For induced NO synthesis, states of overexpression exist.


CONCLUSIONS
Understanding the regulation and function of the enzymes that produce NO and the unique characteristics of each enzyme isoform is likely to lead to therapeutic approaches to prevent or treat a number of diseases.
Billiar
T R
TR
Department of Surgery, University of Pittsburgh, Pennsylvania, USA.
D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D004730:Endothelium, Vascular / Q000201:enzymology; D006801:Humans; D007239:Infections / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000201:enzymology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase
D007527:Isoenzymes; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D009252:NADPH Dehydrogenase