Generation and Reactivity of Lipid Hydroperoxides in Biological Systems

Abstract

AbstractNumerous reviews have been published about the structural/functional damage caused by peroxidation of unsaturated lipids (phospholipids, glycolipids, cholesterol) in model membranes, cellular membranes, and lipoproteins. Less attention has been given to hydroperoxide species (LOOHs), which arise as intermediates of free radical‐mediated (chain) peroxidation or by direct ene‐addition of singlet molecular oxygen. This chapter focuses on nonenzymatic LOOH formation and on LOOH reactivity in biological systems, including cell membranes and lipoproteins. Specialized techniques for analyzing these processes are described. Two competing LOOH reaction pathways are discussed in detail: (i) iron‐catalyzed one‐electron reduction to oxyl radicals (LO•), which expand chain peroxidation, and (ii) enzyme‐catalyzed two‐electron reduction to alcohols (LOH), which inhibits further chain propagation. In addition to these competing fates, LOOHs can undergo spontaneous or protein‐assisted translocation between membranes, lipoproteins, and membranes and lipoproteins, a more recently recognized phenomenon. Intracellular LOOH transfer could result in damage/toxicity enhancement or abatement, depending on prooxidant vs. antioxidant availability. We also discuss a novel, but still poorly understood response to LOOH trafficking, namely, activation of redox signaling pathways. We postulate that LOOHs, unlike the better known signaling molecule, H2O2, will be targeted to relatively hydrophobic “sensor” sites and that these sites are distinct from those targeted by H2O2. Thus, the authors' intent in preparing this chapter was to discuss not only the well‐established chemistry of LOOH generation and turnover, but also LOOH involvement in signal transduction, the importance of which in the field of redox signaling is only beginning to be appreciated.