Lipid peroxidation of n3 and n6 polyunsaturated fatty acids: their impact on membrane structure and cell signaling

FAGALI, N. S.; CATALÁ, A.

POLYUNSATURATED FATTY ACIDS: SOURCES, ANTIOXIDANT PROPERTIES AND HEALTH BENEFITS

Nova Science Publishers

Lugar: New York; Año: 2013; p. 199 - 211

During the last four decades the interest in polyunsaturated fatty acids (PUFAs) has augmented progressively, and the number of published studies is rising each year. The current impetus for this interest has been mainly the observation that PUFAs and their metabolites have a multiplicity of physiological roles including: energy provision, membrane structure, cell signaling and regulation of gene expression, among others. In addition the observation that PUFAs are targets of lipid peroxidation opens a new important area of investigation. This chapter describes the behavior of PUFAs in nature with emphasis on biological membranes and the lipid peroxidation of n-3 and n-6 PUFAs. Eighty years ago, Burr and Burr, introduced for the first time the concept of essential fatty acids. Now is very well known that requirements for PUFAs cannot be met by de novo metabolic processes within mammalian tissues. Animals are absolutely dependent on plants for providing the two major precursors of the n-6 and n-3 fatty acids: C18:2 n- linoleic and C18:3 n-3: α-linolenic acids. In animal tissues these precursors are transformed to fatty acids containing three to six double bonds. Membrane phospholipids containing PUFAs are particularly susceptible to oxidation and can contribute in chain reactions that amplify damage to biomolecules. Lipid peroxidation often occurs in response to oxidative stress, and a great diversity of phospholipid oxidation products and aldehydes is formed when lipid hydroperoxides break down in biological systems. Lipid peroxidation of n-3 and n-6 PUFAs generates hydroxyl-alkenals as: 4-hydroxy-2-hexenal (4-HHE) and 4-hydroxy-2-nonenal (4-HNE), respectively. These aldehydes are highly reactive and may be considered as second toxic messengers which disseminate and augment initial free radical events. During lipid peroxidation, biomolecules such as proteins or amino-lipids, can be covalently modified by these lipid decomposition products, which damage membrane structure modifying its physical properties. In addition, this chapter provides a synopsis of identified effects of hydroxy-alkenals and oxidized phospholipids on cell signaling, from their intracellular production, to their action as intracellular messenger, up to their influence on transcription factors and gene expression.