AbstractThere are two series of essential fatty acids (EFAs), the n-6 and the n-3, derived respectively from linoleic acid and alpha-linolenic acids. The EFAs are important in the structure of membranes, as precursors of eicosanoids, in the transport of cholesterol, and in the structure of the water permeability barrier of the skin. The main dietary EFAS are metabolized to the derived EFAs by a series of alternating desaturations and elongations, the desaturations being slow and rate-limiting and the elongations being rapid. Dietary deficiencies of EFAs are rare, but there is evidence of defective desaturation in diabetes, atopic eczema, breast pain, and premenstrual syndrome. 6-Desaturation may also be impaired by aging, by high levels of cholesterol or alcohol, and in certain cancer cells and virally infected cells. There may be increased utilization of derived EFAs, with inadequate replacement because of the rate-limiting nature of the desaturation steps. In humans, administration of very large amounts of linoleic acid has never been shown to raise the levels of its metabolites in plasma. Administration of smaller amounts of linoleic acid has no effect on levels of gamma-linolenic acid (GLA) or dihomo-gamma-linolenic acid (DGLA) but does consistently produce a small rise in the level of arachidonic acid (AA). Administration of the linoleic acid metabolite GLA, in contrast, consistently raises the levels of DGLA but has a smaller effect on arachidonic acid. This suggests that linoleic acid may be converted by a linked enzyme sequence to arachidonic acid, while GLA does not enter this sequence. The administration of GLA, therefore, consistently raises the ratio of DGLA and its mctabolttes to AA and its metabolites. This is likely to have desirable effects in many systems.
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