Both a-linolenic acid (18:3n-3)1 and linoleic acid (18:2n-6) are now regarded as nutritionally essential fatty acids. However, all the classic symptoms of essential fatty acid deficiency (dermatitis, growth retardation, infertility) can be completely cured by the n-6 fatty acids alone. These symptoms relate to the biological functions of n-6 fatty acids: 18:2n-6 is a structural component in the ceramides of the water barrier of the skin; arachidonic acid (20:4n-6) is a precursor of eicosanoids, which are local hormones that participate in a number of physiological as well as pathophysiological conditions (e.g. parturition initiation, platelet aggregation, renal electrolyte regulation, blastocyte implantation, and activation of immune cells); (3) n-6 fatty acids possibly also play a role as second messengers in the process of signal transduction across cell membranes (e.g. stearoyl-arachidonyl-glycerol, free 20:4n-6, and oxygenated products of 20:4n-6 or 18:2n-6). However, at present it is unclear whether 20:4n-6 as incorporated into phospholipids fulfills a specific function in membranes beyond the precursor role for eicosanoids.

The understanding of the essentiality of the n-3 fatty acids lags behind. The n-3 fatty acids can in part substitute for the n-6 fatty acids ‹ maybe as a sparring effect ‹ in ameliorating some of the essential fatty acid deficiency symptoms (e.g. growth retardation), but are now considered also to have their own distinct role. Like all other fatty acids a major role of dietary n-3 fatty acids in the organism is to provide energy and carbon atoms. Although eicosapentaenoic acid (20:5n-3) can serve as precursors for ``n-3 eicosanoids'', these, in general, have a much lower potency than those derived from 20:4n-6 and are only formed in considerably amounts in tissues at fairly high dietary intakes of 20:5n-3 and docosahexaenoic acid (22:6n-3). Apart from oxidation the sole fate of dietary 18:3n-3 in the body under normal circumstances is to end up as long chain polyunsaturated fatty acids (LCPUFA3), specifically in the form of 22:6n-3, in cellular membranes. Increasing evidence point to a specific role of 22:6n-3 in membrane function, especially in the retina and in neuronal tissues. Thus, it is now generally accepted that n-3 fatty acids are indeed essential in their own nature, but it is currently debated whether dietary 18:3n-3 can fulfill the needs or whether intake of preformed 22:6n-3 is necessary.

In this review we will focus on the metabolism of n-3 fatty acids and attempt to review the current understanding of how the n-3 fatty acid content of neuronal membranes is regulated. Furthermore, we will outline possible mechanisms that may explain how 22:6n-3 can influence the function of neuronal membranes. Finally, we will provide a review on the functional effects of dietary long chain n-3 fatty acids, especially in human infants, and try to understand these results in the context of n-3 fatty acid metabolism.