Paraoxonase (PON1) in Health and Disease: Basic and Clinical Aspects
McQueen, Charlene A., Environmental Health Perspectives
Edited by Lucio G. Costa and Clement E. Furlong Boston, MA: Kluwer Academic, 2002. 216 pp. ISBN: 1-4020-7282-1, $95 cloth.
Paraoxonase (PON1) in Health and Disease: Basic and Clinical Aspects is a complete and timely review of the biochemistry, genetics, and toxicology of the enzyme paraoxonase. The 10 chapters in the volume provide a comprehensive summary of the current knowledge concerning PON1. The history of the discovery and the biochemical characterization of the enzyme set the stage for the subsequent discussion of the genetic polymorphisms, role in lipid metabolism, atherosclerosis and disease, species variation, and organophosphate toxicity.
The discovery of this genetic polymorphism predated the Human Genome Project and illustrates how pharmacogenetics had to be done in the pregenomic era. The story of PON1 begins with the identification of an enzyme having organophosphates as substrates. Reports of the geographic differences in population frequencies of paraoxonase activity and genetic analysis led to uncovering the genetic polymorphism. At the time, the ramifications of the polymorphism seemed to be limited to populations exposed to a relatively discrete group of xenobiotics. But that was only the beginning, as astute observations led to uncovering a physiologic mechanism through which PON1 protects against oxidative damage of low-density lipoproteins. Subsequently, PON1 has been shown to be a risk factor for coronary artery disease. There are also data implicating PON1 in other diseases and in Gulf War Syndrome, although more research is needed is these areas. This scientific history of PON1 is an excellent example of how genetics, toxicology, biochemistry, and physiology work in concert to understand the basis of human health. …