On the physiological role(s) of the paraoxonases

In recent years several lines of evidence have indicated that serum paraoxo nase (PON1), and perhaps other mammalian paraoxonases, act as important gua rdians against cellular damage from toxic agents, such as organophosphates, oxidized lipids in the plasma low density lipoproteins (LDL), and against bacterial endotoxins. For some of these protective activities but not all, PON1 requires calcium ion. The catalyzed chemical reactions generally seem to be hydrolytic, but for some types of protection this may not be so. Seve ral other metals have very high affinity for PON1 and may displace calcium. Replacement or substitution of calcium by other metals could extend the ra nge of catalytic properties and the substrate specificity of the paraoxonas es, as it does for the mammalian DFPases. Although this Third International Meeting on Esterases Reacting with Organophosphorus Compounds focuses on t he organophosphatase activities of paraoxonase and related enzymes, it is i mportant to also briefly review some of the current directions in several l aboratories searching for additional functions of the paraoxonases to exten d our understanding of the properties of this family of enzymes which now s eem to have both physiological and toxicological importance. (C) 1999 Elsev ier Science Ireland Ltd. All rights reserved.