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A synopsis of the process of lipid peroxidation since the discovery of the essential fatty acids

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Abstract

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 polyunsaturated fatty acids PUFAs can not 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, C18:2n-6; linoleic and C18:3n-3; α-linolenic acids. In animal tissues these precursors are transformed to fatty acids containing three to six double bonds. During the last four decades the interest in polyunsaturated fatty acids has augmented manifolds, 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 several physiological roles including: energy provision, membrane structure, cell signaling and regulation of gene expression. In addition the observation that PUFAs are targets of lipid peroxidation opens a new important area of investigation. Melatonin, the main secretory product of the pineal gland, efficiently scavenges both the hydroxyl and peroxyl radicals counteracting lipid peroxidation in biological membranes. In addition the two key pineal biochemical functions, lipoxygenation and melatonin synthesis may be synergistically regulated by the status of n-3 essential fatty acids. At the retina level, free radicals may preferentially react with the membrane polyunsaturated fatty acids leading to the release of lipoperoxide radicals. These lipoperoxides can induce oxidative stress linked to membrane lysis, damage to neuronal membranes may be related to alteration of visual function.

Research highlights

► Eighty years ago, Burr and Burr, introduced the concept of essential fatty acids. ► Plants provides to animals the two major precursors of the n-6 and n-3 fatty acids. ► Lipid peroxidation generates hydroxy-alkenals active in physiological and/or pathological conditions. ► Melatonin, the main secretory product of the pineal gland counteracts lipid peroxidation. ► In the retina, free radicals reacts with PUFAs leading to the release of lipoperoxide radicals.

Section snippets

The discovery of essential fatty acids

In the years 1927 and 1929, two discoveries were made almost at the same time: vitamin E [1] and the essential unsaturated fatty acids [2].

Five decades ago PUFAs were of negligible interest, for their only value was as constituents of drying oils. They were known to be components of nutritional fats, but were considered to be functional only as a source of calories. In 1929, George Oswald Burr and his wife, Mildred, published a paper [2] which discovered that elimination of fat from the diet of

The nature and role of fatty acids essential in nutrition

Requirements for PUFAs can not 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, C18:2n-6; linoleic and C18:3n-3; α-linolenic acids. In animal tissues these precursors are transformed to fatty acids containing three to six double bonds [5]. In animals, some of the daily requirements in long chain PUFAs are satisfied from the diet. However, most of the long chain PUFAs

Synthesis and metabolism of n-3 and n-6 polyunsaturated fatty acids in mammals

Linoleic and linolenic acids cannot be synthesized de novo by mammals and are hence essential in the diet. The n-3 fatty acids, especially eicosapentanoic acid (C20:5n-3) and docosahexanoic acid (22:6n-3) can be obtained from high-fat fish and marine mammals, while the n-6 fatty acids are concentrated in organ meats and vegetable oils.

Linoleic acid, 20:4n-6 and 22:6n-3, are well-known PUFA in cellular phospholipids. Fig. 1 depicted the synthesis of unsaturated fatty acids in mammals.

First evidences for the peroxidation of lipids

The first evidences for the peroxidation of lipids were published by the Swiss chemist Nicolas – Theodore de Saussure in the book “Recherches chimiques sur la végétation” in Paris 1804. In his book he described the principal components of plants, their synthesis and decomposition. New observations on the chemical performance of plant lipids lay the basis of the understanding of their oxidative properties.

Lipids are a heterogeneous group of compounds having numerous significant functions in the

The lipid peroxidation process, basic concepts

Oxidative stress that occurs in the cells, because an imbalance between the prooxidant/antioxidant systems, cause damage to biomolecules such as nucleic acids, proteins, structural carbohydrates and lipids [24]. The general process of lipid peroxidation consists of three stages: initiation, propagation and termination [25]. The initiation phase of lipid peroxidation includes hydrogen atom abstraction. Several species can abstract the first hydrogen atom and include the radicals: hydroxyl (radical dotOH),

Lipid peroxidation of n-3 and n-6 polyunsaturated fatty acids

A great diversity of aldehydes is formed when lipid hydroperoxides break down in biological systems. Some of these aldehydes are highly reactive and may be considered as second toxic messengers, which disseminate and augment initial free radical events. 4-Hydroxy-2-nonenal (HNE) is known to be the main aldehyde formed during lipid peroxidation of n-6 polyunsaturated fatty acids, such as linoleic acid C18:2 n-6 and arachidonic acid C20:4 n-6.

On the other hand, lipid peroxidation of n-3

Fatty acids can modulate the cellular production of reactive oxygen species

Reactive oxygen species are a by-product of mitochondrial oxidative phosphorylation, derived from a little amount of superoxide radicals generated during electron transport. Investigations by various groups and using different cell types have shown that changes in the level of nonesterified fatty acids can influence the rate of reactive oxygen species (ROS) production and consequently are likely to be one of the physiological factors controlling oxidative stress. Stimulation of cellular ROS

n-3 and n-6 polyunsaturated fatty acids play important functions in the pineal gland

Arachidonic (C20:4-n6) and docosahexaenoic (C22:6n-3) acids are the main polyunsaturated fatty acids of the n-6 and n-3 families respectively, that are specifically found in the pineal gland [33] as well as in some particular tissues, including, retina and neural tissues [34].

The mammalian pineal gland is a prominent secretory organ with a high metabolic activity. Melatonin (N-acetyl-5-methoxytryptamine), the main secretory product of the pineal gland, efficiently scavenges both the hydroxyl

At retinal level free radicals preferentially react with n-3 polyunsaturated fatty acids

The retina contains very high levels of 22:6n-3 representing the highest concentration of PUFAs of any vertebrate tissue [37]. In fact, 50% of all acyl chains in the outer segments of photoreceptors phospholipids (both sn-1 and sn-2) are 22:6n-3 (in PC, PE, and PS). Minor phospholipids, like phosphatidylinositol and phosphatidic acid, contain predominantly 20:4n-6 [38]. Thus, rod outer segments represent an excellent model to define the role of 22:6n-3 in membrane structure and function.

Concluding remarks

It is clear that mammalian tissues contain high levels of arachidonic and docosahexaenoic acids that are the main polyunsaturated fatty acids of the n-6 and n-3 families, respectively. 4-Hydroxy-2-nonenal (HNE) is known to be the main aldehyde formed during lipid peroxidation of n-6 polyunsaturated fatty acids, such as linoleic acid C18:2 n-6 and arachidonic acid C20:4 n-6. On the other hand, lipid peroxidation of n-3 polyunsaturated fatty acids such as α-linolenic acid C18:3 n-3 and

Acknowledgments

Studies in the author laboratory were supported by PIP 2008-0157 National Research Council (CONICET).

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    The author is Member of Consejo Nacional de Investigaciones Cientificas y Técnicas Argentina.

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