Metabolism Y-linolenic acid

Y. S. Huang and D. E. Mills, eds., y-Linolenic Acid Metabolism and its Roles in Nutrition and Medicine, American Oil Chemists Society, Champaign, Illinois, 1996. 

Karlstad MD, Palombo JD, Murray MJ, Demichele SJ. 1996. The antiinflammatory role of y-linolenic and eicosapen-taenoic acids in acute lung injury. In y-Linolenic Acid Metabolism and Its Roles in Nutrition andMedicine, ed. YS Huang, DE Mills, pp. 137-67. Champaign AOCS... 

Phillips. J.C.. and Huang, Y.-S. (1996) Natural Sources and Biosynthesis of y-Linolenic Acid An Overview, in y-Linolenic Acid Metabolism and Its Roles in Nutrition and Medicine (Huang,Y.-S., and Mills, D.E., eds.) pp. 1-13, AOCS Press, Champaign, IL. 

F.D. Gunstone, Gamma linolenic acid — occurrence and physical and chemical properties. Progress in Lipid Research, 1992, 31, 145-161. D.F. Horrobin, Nutritional and medical importance of gamma-linolenic acid, Progress in Lipid Research, 1992, 31, 163-194. y-Linolenic Acid — Metabolism and its Roles in Nutrition and Medicine, Y.-S. Huang and D.E. Mills (eds), AOCS Press, Champaign, Illinois (1995). 

Experiences in cat nutrition underscore the fallacy of assuming that metabolic pathways found in one species are automatically present in others. Early studies on metabolism of PUFA were conducted on rats, which have high A6 and A5 desa-turase abilities to convert linoleic acid (18 2n-6) to the prostaglandin precursors dihomo-y-linolenic acid (20 3 -6) and arachidonic acid (20 4 -6), respectively. This led to the assumption that other species can desaturate polyunsaturated fatty acids equally well. Over a period of time, it was shown that cats are not able to convert 18 2 -6 to 20 3n-6 or 20 4 -6. The NRC currently recommends the inclusion of 5 g linoleic acid and 0.2 g arachidonic acid/kg diet dry matter. 

A double bond within the terminal seven carbon atoms can be present at o>-3 or co-6. y-Linolenic acid is an a>-6 EFA and a-linolenic acid an rw-3 EFA. Other co-3 EFA are eicosapentaenoic acid (EPA) and docosahexaenoic acid (EX)HA), both abundant in edible fish tissues. Vegetable oils are rich in rw-6 EFA (Table 18-4). Plants contain a-linolenic acid, which can be converted in the body to EPA and DOHA, but it is found within chloroplast membranes and not in seed oils hence, it may not be available in significant quantities in the diet. The a>-3 and o)-6 EFA have different metabolic effects (see below). Particularly rich sources of EPA are fishes (e.g., salmon, mackerel, blue fish, herring, menhaden) that live in deep, cold waters. These fishes have fat in their muscles and their skin. In contrast, codfish, which have a similar habitat, store fat in liver rather than muscle. Thus, cod liver oi I is a good source of EPA, but it also contains high amounts of vitamins A and D, which can be toxic in large quantities (Chapters 38 and 37, respectively). Shellfi.sh also contain EPA. Plankton are the ultimate source of EPA. 

Workers at Lilly have reported the synthesis of 8,9-LTA3 (51), 8,9-LTC3 (52a), and 8,9-LTD3 (52b),leukotrienes that are reported to be produced from dihomo-y-linolenic acid in ionophore-stimulated murine mastocytoma cells. The natural stereochemistry was assumed to be (85,9/f,10,12 ,14Z) by analogy with arachidonic acid metabolism in the same cell system. The chiral synthesis was achieved (93% ee) via Sharpless epoxidation of an appropriate allylic alcohol (53) (Scheme 5.17). 

The metabolic pathways for synthesis of n-6 and n-3 families of polyunsaturated fatty acids from the essential fatty acids, linoleic acid (LA) (18 2 [n-6]) and a-linolenic acid (18 3 [n-3]), respectively, are showninFig. 2. Conversion of LA to arachidonic acid (AA) occurs via A6 desaturation to yield y-linolenic acid (GLA), then an elongation step to produce dihomo-y-linolenic acid (DHGL A) and A5 desaturation, to form AA. The A6 and A5 microsomal desaturases have been reported to utilize both NADH and NADPH as cofactors in vitro (Brenner 1977). Whether there is a more stringent pyridine nucleotide requirement in vivo is not known with certainty. Desaturase activities are especially abundant in the liver. 

Fig. 5. Metabolism of dietary linoleic acid (LA) and y-linolenic acid (GLA) in epidermis. Abbreviations DGLA, dihomo-y-linolenic acid AA, arachidonic acid 15-LOX, 15-lipoxyge-nase 13-HODE, 13-hydroxyoctadecadienoic COX, cyclooxygenase PGE, prostaglandin E, 15-HETrE, 15-hydroxyeicosatrienoic acid.

Epidemiological studies have revealed a positive correlation between the proportions of palmitoleic acid, y-linolenic acid (GLA 18 3n-6), and dihomo-y-linolenic acid (DGLA 20 3n-6) in serum cholesterol esters and the incidence of glucose intolerance and non-insulin-dependent diabetes mellitus (Vessby et al., 1994). There is also a correlation between the level of palmitoleic acid in serum and the risk of developing non-insulin-dependent diabetes mellitus. This may be attributable to dietary factors but there is a strong possibility that genetically determined differences in the activities of enzymes involved in the synthesis and metabolism of fatty acids in the body may contribute to the correlation. This occurs through the effects of the enzymes on lipid composition and on insulin sensitivity (Borkman et al, 1993). 

Palombo, JD, DeMicheUe, SJ, Liu, JW, Bistrian, BR and Huang, YS (2(XX)) Comparison of growth and fatty acid metabolism in rats fed diets containing equal levels of y-linolenic acid from high y-Unolenic acid canola oil or borage oil. Lipids, 35, 975-981. 

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