Plants possess two enzymes, Δ12-desaturase and Δ15-desaturase, that allow the synthesis of linoleic acid (LA, C18:2 (n-6)) and α-linolenic acid (ALA, C18:3 (n-3)), respectively. The Δ12-desaturase enzyme adds a double bond to a molecule of oleic acid (OA, C18:1 (n-9)) to form LA, and the Δ15-desaturase enzyme adds a double bond to LA to form ALA. The fatty acids ALA and LA belong to the n-3 and n-6 family of fatty acids, respectively. The group nomenclature is based on the number of carbon atoms from the methyl end before the first double bond. Humans and animals do not possess Δ12-desaturase and Δ15-desaturase, and because LA and ALA are required for cell function, they become essential dietary components. Both LA and ALA in humans and animals are metabolised to longer more highly unsaturated fatty acids through a series of elongase and desaturase enzymes, the reactions of which are mainly hepatic.
The enzyme Δ6-desaturase is the first and rate-limiting step in the metabolic pathway that converts ALA to docosahexanoic acid (DHA, C22:6 (n-3)). This enzyme converts ALA to stearidonic acid (SDA, C18:4 (n-3)) by addition of a double bond. Subsequently, SDA is elongated to eicosatetraenoic acid (ETA, C20:4 (n-3)) through addition of two carbon molecules to the fatty acid chain. The second desaturase enzyme, Δ5-desaturase then converts ETA to eicosapentanoic acid (EPA, C20:5 (n-3)) through addition of another double bond. Each additional double bond confers a greater degree of curvature to the molecule, which alters its biological properties and increases cell membrane fluidity. Eicosapentanoic acid is converted to docosapentanoic acid (DPA, C22:5 (n-3)) through the action of an elongase enzyme, adding two carbons. Finally DHA is synthesised through the action of Δ6-desaturase, elongase and limited peroxisomal β-oxidation. Studies suggest that the conversion of ALA to DHA in poor in humans.
Understanding the enzymatic steps of the n-3 pathway is important because n-3 fatty acids compete for their enzymes with n-6 fatty acids. This is of interest because whereas the n-3 fatty acids tend to be converted to compounds with anti-inflammatory, anti-thrombotic and immune stimulatory properties, those of the n-6 pathway can form compounds with pro-inflammatory pro-thrombotic and immune suppressing properties. Competition between the n-6 and n-3 fatty acid classes for the elongase and desaturase enzymes therefore regulates important cellular functions. For example, conversion of LA to γ-linolenic acid (GLA, C18:3 (n-6)) uses the same Δ6-desaturase enzyme as the conversion of ALA to SDA. Subsequently GLA is elongated to dihomo-γ-linolenic acid (DGLA, C20:3 (n-6)), followed by desaturation to arachidonic acid (AA, C20:4 (n-6)) using the Δ5-desaturase enzyme. The ratio of the dietary intake of n-3 to n-6 fatty acids therefore has an influence on the products from this pathway.
Increasing n-3 fatty acid intake, may therefore confer health benefits to humans and animals, particularly in terms of protecting from diseases of inflammation such as cardiovascular disease. The fatty acids of green leafy vegetables comprise about 50 % ALA, but because they are eaten is such low amounts and contain such little fat, they are poor sources of n-3 fatty acids. The fatty acids in flax seeds comprise around 50 % ALA, and fatty acids in other oils such as soy, rapeseed and walnut comprise around 10% ALA. Lean cold water fish such as cod store fatty acids in their livers, but tuna, mackerel, herring, salmon, trout and sardine store their fatty acids in their flesh and so are described as fatty fish. Fatty fish and fish liver oil contains EPA and DHA in differing ratios depending on the species, temperature, location and their diet.
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