Understanding genetic defects and their effects on metabolic pathways can be useful in the nutritional sciences. This is because diet can influence enzyme activity to a similar extent as genes. For example, Kilmer McCully identified homocysteine as a causative factor in cardiovascular disease through the study of patients with homocysteinurea. Cystic fibrosis is of interest to the nutritional sciences because one of the features of the condition is a abnormal metabolism of the long chain fatty acids linoleic acid (LA, C18:2 (n-6)) and α-linolenic acid (ALA, C18:3 (n-3)). This abnormality results in decreased tissue levels of docosahexanoic acid (DHA, C22:6 (n-3)) but increased tissue concentrations of arachidonic acid (AA, C20:4 (n-6)). This may results from increased expression and activity of fatty acid desaturase enzymes, in the conversion of the dietary essential fatty acids LA and ALA, to the longer chain EPA, DHA and AA.
Researchers1 have investigated the effects of exogenous EPA and DHA on the fatty acid composition and metabolism of human bronchial cells. In particular, the researchers were interested in the expression of the desaturase enzyme following administration of fatty acids. The researchers used a cell culture model of cystic fibrosis to investigate these effects by supplementing the cell media with various concentrations of fatty acids. Addition of both EPA and DHA to the cell culture media resulted in a decrease in expression of both Δ5-desaturase and Δ6-desaturase. This had the effect of decreasing the flux through the essential fatty acid pathways. This decreased flux resulted in a reduction in the concentration of AA. Also of interest, the authors reported an increased retro-conversion of DHA to EPA in the cystic fibrosis cell model, suggesting that the Δ4-desaturase enzyme activity may have persisted.
Although results from cell models should be treated with extreme caution, this work does support previous findings from animal and humans studies. Both EPA and DHA appear to regulate the Δ5- and Δ6-destaurase enzymes that are pivotal to the essential fatty acid pathway. These results suggest that EPA and DHA supplementation may alleviate some of the abnormal fatty acid metabolism seen in cystic fibrosis sufferers, and this may have implications for healthy individuals. If increased intakes of EPA and DHA are able to decrease the expression and activity of the Δ5-desaturase and Δ6-desaturase, this may explain a significant part of the anti-inflammatory effects of supplemental fish oils. Decreasing flux through the pathway would decrease the production of AA and its pro-inflammatory metabolites. Further, decreased activity of the Δ5-desaturase enzyme may allow accumulation of dihomo-γ-linolenic acid (DGLA, C20:3 (n-6)) which may further cause a decrease in inflammation.
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