Omega-3 fatty acid metabolism

C. A. Drevon, I. Baksaas, and H. L. Krokan, eds., Omega-3 Fatty Acids Metabolism and Biological Ejfects., Birkhauser Verlag, Basel, 1993. 

There are clear abnormalities of fatty acid concentrations in depression that are distinct from those in schizophrenia (Adams, Lawson, Sanigorski, Sinclair, 1996 Maes et al., 1996 Maes et al., 1999 Peet, Murphy, Shay, Horrobin, 1998 Edwards, Peet, Shay, Horrobin, 1998). Eirst, the abnormalities are present in both plasma and in red cells, raising the possibility that the problem may be in fatty acid metabolism in general, rather than membrane phospholipid metabolism in particular. Second, the abnormalities are specifically deficits in the omega-3 fatty acids EPA, DHA, and docosapentaenoic acid (DPA), and particularly in EPA. In contrast to the situation in schizophrenia, AA levels are either normal or elevated. 

Sprecher, H. (1986) Comparison of Omega-3 and Omega-6 Fatty Acid Metabolism in Health Effects of Polyunsaturated Fatty Acids (Simopoulos, A.P., Kifer R.R., and Martin, R., eds.) pp. 353-379, Academic Press, Orlando. 

Hardwick JP (2008) Cytochrome P450 omega hydroxylase (CYP4) function in fatty acid metabolism and metabolic diseases. Biochem Pharmacol 75 2263-2275... 

Nguyen, H.T., Mishra, G., Whittle, E., Bevan, S.A., Owens-Merlo, A., Walsh, T.A. and Shanklin, J. 2010. Metabolic engineering of seeds can achieve levels of omega - fatty acids comparable to the highest levels found in natural plant sources. Plant Physiol. 154 1897-1904. 

See also Antioxidants Diet and Antioxidant Defense. Coronary Heart Disease Lipid Theory Prevention. Fatty Acids Metabolism Monounsaturated Omega-3 Polyunsaturated Omega-6 Polyunsaturated Saturated Trans Fatty Acids. 

Fischer, M.A. and Black, H.S., Modification of membrane composition, eicosanoid metabolism, and immunoresponsiveness by dietary omega-3 and omega-6 fatty acid sources, modulators of ultraviolet-carcinogenesis, Photochem. Photobiol., 54, 381, 1991. 

Watkins, B. A., Li, Y., Lippman, H. E., and Feng, S. 2003. Modulatory effect of omega-3 polyunsaturated fatty acids on osteoblast function and bone metabolism. Prostaglandins, Leukot. Essent. Fatty Acids, 68, 387-398. 

Cleavage of the ether linkage of the 2,4-dichlorophenoxyalkanoic acids by a strain of Flavobacterium to yield the intact alkanoic acid and 2,4-dichlorophenol has also been observed (34,35). The intact alkanoic acid is further metabolized by beta oxidation. The bacterium produced the free fatty acid corresponding to the aliphatic moieties of six omega-linked dichlorophenoxyalkanoic acids in the series from 3-(2,4-dichloro-phenoxy) propionic acid to 8-(2,4-dichlorophenoxy)octanoic acid. 

Aside from sophisticated drug design, there is a surprisingly simple means of favourably influencing the balance of Good and Evil in eicosanoid metabolism Eating fish. As initially mentioned, aside from arachidonic acid, other multiply non-saturated fatty acids can serve as precursors of eicosanoid mediators as well, in particular eicosapentanoic acid (EPA), which has an additional double bond between C17 and Cl8. The introduction of this omega-3 double bond does not occur, nor is it reversible, in mammalian... 

Figure 12.16. Omega-3 fatty acids and their relevance to prostaglandin metabolism, a Omega-3 nnsatnrated fatty acids are derived from linoleic acid by a special desatnrase fonnd in plants bnt not in mammals. They are particnlarly common in cold-waterfish. b The different nnmbers and positions of donble bonds persist in the eicosanoids derived from different fatty acid precnrsors, giving rise to different homologons derivatives. This is shown here for prostaglandin E. c Biological activity of the eicosanoids derived from eicosapentanoic acid (EPA).

Rustan AC, Nenseter MS, and Drevon CA (1997). Omega-3 and omega-6 fatty acids in the insulin resistance syndrome. Upid and lipoprotein metabolism and atheroscloosis. Amuds New York Acad. Sciences 827,310-326. 

Oliw, E.H. and Sprecher, H.W. (1991) Metabolism of polyunsaturated (n-3) fatty acids by monkey seminal vesicles isolation and biosynthesis of omega-3 epoxides. Biochim. Biophys. Acta. 1086 287-294. 

Linoleic acid and LNA and their long-chain derivatives arc important components of animal and plant cell membranes. When humans ingest fish or fish oil, the EPA and DHA from the diet partially replace the omega-6 fatty acids, especially AA, in the membranes of probably all cells, but especially in the membranes of platelets, erythrocytes, neutrophils, monocytes, and liver cells [reviewed in Simopoulos, 19911. A diet that has a high ratio of omega-6 omega-3 fatty acids has detrimental effects on eicosanoid metabolism and gene expression. 

A balance between the omega-6 and omega-3 fatty acids is a more physiologic state in terms of gene expression (Simopoulos, 1996), prostaglandin and leukotriene metabolism, and interleukin-1 (IL-1) production (Simopoulos, 1991). The current recommendation to substitute vegetable oils (omega-6) for saturated fats leads to increases in IL-1,... 

Fig. 3. The metabolism of the omega-6 and omega-3 essential fatty acid.

Alpha-linolenic acid (LNA or 18 3n-3) An 18-carbon, three double-bond fatty acid in the omega-3 family. This polyunsaturated fatty acid is produced in the chloroplast of terrestrial and marine plants. In animals, alpha-linolenic acid is metabolized into the longer-chain omega-3 fatty acids, eicosapentaenoic acid, and docosahexaenoic acid. 

Bazan, N.G. (1989). The metabolism of omega-3 polyunsaturated fatty acids in the eye the possible role of docosahexaenoic acid and docosanoids in retinal physiology and ocular pathology. Prog Clin Biol Res 312, 95-112. 

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