Omega-6 Fatty Acids
KeywordsLinoleic Acid Arachidonic Acid Fatty Acid Methyl Ester Docosapentaenoic Acid Fatty Acid Omega
Omega-6 fatty acids contain their last double bond in the alkenic chain six carbon atoms from the fatty acid omega end and are generally essential fatty acids for humans. This means that they cannot be synthesized by simple elongation or desaturation steps of palmitic (FA 16:0), stearic (FA 18:0), or oleic acid (FA 18:1) by our organism and consequently have to be taken up by diet. The starting point for synthesis of most omega-6 fatty acids is linoleic acid (FA 18:2) which is sequentially elongated and desaturated into other long chain and very long chain omega-6 fatty acids. Linoleic acid is the most commonly found omega-6 fatty acid in plants and animals but can only be produced by plants. The major sources are sunflower and soybean with up to 50 % of linoleic acid.
γ-Linolenic acid (FA 18:3 ω-6) is the first desaturation product of linoleic acid and therefore an intermediate at the pathway from linoleic acid to higher omega-6 fatty acids. It can be found in substantial proportions exceeding 1 % of fatty acid composition only in some plants, e.g., primrose where it was isolated first in 1919.
Arachidonic acid (FA 20:4 ω-6) is the most important omega-6 fatty acid. This is not due to its relative contribution to the lipidome, but rather due to the oxidized signaling compounds synthesized from arachidonic acid. Most of the eicosanoids formed from arachidonic acid are pro-inflammatory autocrine and paracrine agents. In phospholipids, arachidonic acid is mostly esterified at the sn-2 position. Liberation of arachidonic acid from phospholipids within cellular systems is catalyzed by phospholipase A2, particularly subtype IV (cPLA2). This enzyme is translocated to the membrane by intracellular Ca2+. The liberated arachidonic acid is immediately metabolized to eicosanoids by oxygenating enzymes like cyclooxygenase (COX) or lipoxygenase (LOX). The most important source of arachidonic acid for humans is meat and to some extent also fish.
Docosapentaenoic acid (FA 22:5 ω-6) and its precursors tetracosatetraenoic acid (FA 24:4 ω-6) and tetracosapentaenoic acid (FA 24:5 ω-6) are found in significant amounts in testes. These fatty acids are thought to have an important role in maturation of testes.
Shorter chain omega-6 fatty acids like FA 14:2 can be produced by beta oxidation of long chain or very long chain omega-6 fatty acids.
An important pathophysiological reaction of all polyunsaturated fatty acids but due to their relatively high abundance in particular of arachidonic acid and linoleic acid is lipid peroxidation. Lipid peroxidation happens at an excess of free oxygen radicals in cellular systems (oxidative stress), especially in mitochondria. Importantly, this is a nonenzymatic chemical process, whereby allylic methylene groups preferably in between two double bonds react with oxygen by hydrogen abstraction. The resulting lipid peroxide radical then further reacts by either fatty acid chain truncation and/or formation of fatty acids containing hydroxy, oxo, or carboxy moieties as additional functional groups. Lipid peroxidation is an important process in atherosclerosis and inflammation-related diseases (Esterbauer et al. 1992).