Dihomo-y-linolenic acid

Fig. 2. (a) The basis for prostaglandin nomenclature, where the letters A—F and J define principal families (b) defines the side chains for PG derived from dihomo-y-linolenic acid (c) PG2 derived from arachidonic acid and (d), PG derived from eicosapentaenoic acid. 

Diethylenetriaminepentaacetic acid DFMO al-Difluoromethyl ornithine DFP Diisopropyl fluorophosphate DFX Desferrioxamine DGLA Dihomo-y-linolenic acid DH Delayed hypersensitivity DHA Docosahexaenoic acid DHBA Dihydroxybenzoic acid DHR Delayed hypersensitivity reaction... 

The question arises whether inhibition of the desaturase for this particular pathway can be overcome. The answer is yes. The product of the A desaturase when desaturating linoleic acid is y-linolenic acid. Supplementation of the diet with y-linolenic acid, which bypasses the A desaturase reaction, has been used to increase the formation of dihomo-y-linolenic acid and arachidonic acid (Figure... 

Nagao, T., Watanabe, Y., Kobayashi, T., Sumida, M., Kishimoto, N., Fujita, T., and Shimada, Y. 2007. Enzymatic purification of dihomo-y-linolenic acid from Mortier-ella single-cell oil. J. Mol. Catal. B Enzym., 44,14-19. 

Bioproducts Enriched with Dihomo-y-Linolenic Acid (DGLA)... 

Huong L. M., Slugen D., Sajbidor J. 1998. Production of dihomo-y-linolenic acid by... 

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 defect in the capability of the enzyme 5-6-desaturase to convert linoleic acid to y-linolenic acid is known to occur in patients with atopic dermatitis (9). Patients with atopic eczema have a dietary deficiency in metabolites of linoleic y-linolenic acid, dihomo-y-linolenic acid, arachidonic acid, adrenic acid, and docosapentaenoic acid caused by a reduced rate of activity in the 5-6-desturase enzyme (8). Galli et al. compared blood samples from babies born to parents who suffered from atopic eczema. Results showed... 

Increased concentrations of eicosanoids (leukotriene B4, prostaglandin E2 [PGE2] and thromboxane A2) have been reported to exist in the colon mucosa and rectal areas of patients with ulcerative colitis (14). In 1993, a randomized, placebo-controlled study was conducted by Greenfield et al. examining the effect of OEP and fish oil supplementation on cell membranes and symptom control in 43 patients diagnosed with stable ulcerative colitis. Treatment with OEP increased red-cell membrane concentrations of dihomo-y-linolenic acid by 40% at 6 months (p < 0.05), and compared to MaxEPA and placebo, OEP significantly improved stool consistency at 6 months, with... 

Low levels of linoleic acid and dihomo-y-linolenic acid may predispose coronary heart disease (6,40). For this benefit, linoleic acid needs to be converted by the enzyme 8-6-desaturase to other highly unsaturated, long-change fatty acids, such as y-linolenic acid. OEP contains both linoleic and y-lino-lenic acid, and OEP has been reported to reduce elevated serum cholesterol levels, with y-linolenic acid having a more dramatic effect of the two (6). 

Prostaglandins — Dihomo - y - Linolenic acid (1-series) A 5-Desaturase... 

The four groups of eicosanoids are derived, respectively, from a 20-carbon fatty acid with three, four, or five double bonds 8,11,14-eicosatrienoic acid (dihomo-y-linolenic acid), 5,8,11,14-eicosatetraenoic acid (arachi-donic acid), and 5,8,11,14,17-eicosapentaenoic acid (Figure 18-17). In humans, the most abundant precursor is arachidonic acid. Secretion of eicosanoids in response... 

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. 

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