Review Article

Membrane Omega-3 Fatty Acid Deficiency as a Preventable Risk Factor for Comorbid Coronary Heart Disease in Major Depressive Disorder

Figure 1

Diagram illustrating the biosynthetic pathway of n-3 and n-6 fatty acids from dietary precursors. The biosynthesis of EPA (20:5n-3) and DHA (22:6n-3) from dietary α-linolenic acid (18:3n-3), and arachidonic acid (20:4n-6) from linoleic acid (18:2n-6), requires a series of common and competitive microsomal elongation and delta-5 and delta-6 desaturase-mediated reactions. The final synthesis of DHA requires additional modifications within peroxisomes. Preformed DHA (22:6n-3), the principle membrane esterified n-3 fatty acid, and EPA can be obtained directly from the diet. COX-2 mediated metabolism of DHA and arachidonic acid yields anti-inflammatory docosenoids and proinflammatory eicosanoids, respectively. Because the n-6 and n-3 arms compete for common biosynthetic enzymes, elevations in the dietary LA : ALA ratio increase n-6 fatty acid biosynthesis (reflected as reductions in membrane LA and elevations in downstream fatty acid metabolites) and reduced n-3 fatty acid biosynthesis from ALA (reflected as reductions in membrane EPA+DHA).
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