Docosahexaenoic acid metabolic products

Once ingested, these essential fatty acids can be metabolized into longer, more unsaturated products (Holman, 1968). This process involves sequential desaturation (adding double bonds) and chain elongation (adding carbon atoms), as shown in Fig. 1. The important aspect of Fig. 1 is that the n-6 and n-3 families compete for the enzymes responsible for desaturation (Sinclair, 1993). The main metabolite of the n-6 series is arachidonic acid (20 4n-6, AA), whereas eicosapentaenoic acid (20 5n-3, EPA) and docosahexaenoic acid (22 6n-3, DHA) are the main metabolites ofthe n-3 series (Holman, 1968). The metabolic pathways leading to DHA are complicated by involving retroconversion from 24 6n-3 to 22 6n-3 (DHA) (Voss et al., 1991). 

Dceda, L, Yoshida, H., Tomooka, M., Yosef, A., Imaizumi, K., Tsuji, H., and Seto, A. (1998) Effects of Long-Term Eeeding of Marine Oils with Different Positional Distribution of Eico-sapentaenoic and Docosahexaenoic Acid on Lipid Metabolism, Eicosanoid Production and Platelet Aggregation in Hy-percholesterolemic Rats, Lipids 33,897-904. 

H. S., Muller, R., and Wenzel, S.C. (2016) Metabolic engineering of Pseu-domonas putida for production of docosahexaenoic acid based on a myxobacterial PUFA synthase. Metab. Eng., 33, 98-108. 

Unsaturated fatty acids are probably the most abundant oxidizable endogenous substrates. In the past it was erroneously believed that unsaturated fatty acids are just products of lipid peroxidation. Now, it has been shown that they have dietary origin. Family of unsaturated fatty acids includes linoleic (Ci8), arachidonic (C2o), docosahexaenoic (C22), and other fatty acids containing two, three, four, five, or six double bonds. Some acids can be in vivo converted into others for example, linoleic acid can be metabolized to linolenic and eicosa-trienoic acids [78]. 

Eicosapentaenoic add (Table 6) is easily incorporated into the cell membrane-bound phospholipids. It is a poor substrate for the cyclooxygenase/hydroper-oxidase enzymatic system, and only very small amounts of endproducts with three double bonds will be formed when compared with the relative effectiveness of arachidonate metabolism. In contrast, dcosapentaenoic add is a preferred substrate for product generation by the S-lipoxygenase in subcellular fractions of human and animal neutrophils [66,87], whereas docosahexaenoic add is also a markedly inferior substrate for leukotriene synthesis. Eicosapentaenoic acid appears to inhibit phospholipase activity, resulting in a decrease of aradiidonic acid release ([67] Fig. 4). Moreover, simultaneously with thromboxane A3 and prostaglandin I3 generation from eicosapentaenoic add, the synthesis of thromboxane A2 and prostacyclin (PGIj) from aradiidonic acid [47] decreases, mainly due to inhibitory effects on PGH synthase activity (Fig. 4). 

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