INTRODUCTION

Lipid membranes and the individual lipids that comprise them were initially considered to solely provide eukaryotic cells with organized hydrophobic barriers used to separate cytoplasmic and extracellular environments. Additional studies demonstrated that these lipid bilayer structures also acted as boundaries for discrete intracellular structures, e.g. mitochondria, endosomes, and endoplasmic reticulum. Although this capacity to separate aqueous compartments clearly is an essential feature of normal cell structure and function, more recent studies have demonstrated that lipid components in these bilayer membranes also provide cells with substrates to produce a spectrum of intra- and extracellular messengers. Metabolism of membrane lipid components has been shown to produce bioactive lipids that participate in numerous signaling mechanisms. Many of these bioactive lipids, such as prostaglandins, leukotrienes, hydroperoxy acids, hepoxilins, lipoxins, and thromboxanes, are derived from the metabolic processing of arachidonic acid.

Arachadonic acid, a 20-carbon fatty acid that contains four carbon–carbon double bonds, is the precursor substrate used for the production of a large family of bioactive lipids known as eicosanoids (Fitzpatrick and Soberman, 2001; Lieb, 2001) (Figure 10.1). By itself, arachidonic acid can act as a second messenger by its ability to interact with GTP-binding proteins (Abramson et al.., 1991), inhibit GTPase-activating protein regulated by RAS (Ras-GAP) function (Han et al., 1991), cause the release of Ca2+ ions stored in the sarcoplasmic reticulum (Dettbarn and Palade, 1993), and modulate protein kinase C (PKC) activity (Khan et al., 1995).