Essential fatty acids and the biosynthesis of eicosanoids

Although we do not know the physiological function of lipoxygenase, the effect of the enzyme in plant tissues is to yield volatile products with characteristic flavours and aromas - either desirable or undesirable (section 3.3.4). The substrates for lipoxygenase are the free fatty acids released from storage lipids by lipases (section 4.5) or from membrane lipids (Chapter 7) by non-specific lipolytic acylhydrolases . 

In section 3.2.4 we described the biosynthesis of the polyunsaturated fatty acids and indicated that animals lack the A12 and A15-desaturases. They cannot, therefore, synthesize linoleic or linolenic acids. It turns out, however, that these polyunsaturated fatty acids are absolutely necessary for the maintenance of growth, reproduction and good health and must, therefore, be obtained in the diet from plant foods. They are called essential fatty acids and their role in nutrition and health will be described in detail in section 5.2.2. Chapter 5 will also describe the dual roles of the essential fatty acids and their longer-chain, more highly unsaturated metabolic products in membranes and as precursors of a variety of oxygenated fatty acids with potent biological activities now generally known collectively as the eicosanoids. 

After the structures of PGE and PGF had been defined, the subsequent rapid exploitation of this field, including the unravelling of the biosynthetic pathways, was done almost entirely by two research teams led by van Dorp in Holland and by Bergstrom and Samuelsson in Sweden. Both realized that the most likely precursor of PGE2 and PGF2 was arachidonic acid. This was 

Figu re 3.30 Overall pathway for conversion of essential fatty acids into eicosanoids. 

Prostaglandin H is the key intermediate for conversion to various active eicosanoids. The enzymes responsible for its further metabolism are present 

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Essential fatty acids and the biosynthesis of eicosanoids 103 = /= " COOH... 

FIGURE 5.1 Proposed model for the possible role of 2-arachidonoylglycerol (2-AG) in the synapse. (From Sugiura, T., Kondo, S., Kodaka, T., Nakane, S., Yamashita, A., Kishimoto, S., Waku, K., and Ishima, Y. [1998] Biosynthesis and actions of anandamide and 2-AG two endogenous cannabimimetic molecules, in Essential Fatty Acids and Eicosanoids, Eds., R.A. Riemesma, R. Armstrong, W. Kelly, and R. Wilson, Champaign AOCS Press, pp. 380-384. With permission.)... 

Gryglewski, R.J. (1998) TransceUular Biosynthesis of Eicosanoids in Circulation, in Essential Fatty Acids and Eicosanoids Invited Papers from the Fourth International Conference (Riemersma, R.A., Armstrong, R., Kelly, R.W., Wilson, R., eds.) pp. 202-205, AOCS Press, Champaign, IL. 

In addition, in vivo C MR spectroscopy has been applied to the study of adipose tissue composition in disease. Children with cystic fibrosis were shown to have lower levels of polyunsaturated adipose tissue fatty acids than healthy children, possibly owing to a disorder in essential fatty acid metabolism that may be partly responsible for the development of the disease. Further studies with in vivo MRS in disease have shown a significant increase in saturated adipose tissue fatty acids following transplantation and subsequent weight gain in malnourished patients with liver cirrhosis. It was suggested that this increase in saturated fatty acids may be secondary to a general repletion of membrane polyunsaturated fatty acids or the use of essential fatty acids for biosynthesis of eicosanoids in the postoperative period. 

C20H32O2, Mr 304.47, mp. -49.5 °C, bp. 163°C (133 Pa). A biochemically important essential fatty acid, precursor of various eicosanoids. In animals, A. is formed in several steps from linoleic acid by introduction of 2 double bonds and chain extension by 2 carbon atoms linoleic acid - y- linolenic acid - di-homo-y-linolenic acid arachidonic acid. In nature A. occurs in animal lipids, especially in phospholipids of cell membranes, from which phospholipase A2 releases A. on stimulation by hormones or mediators. A. serves as starting material for the biosynthesis of numerous physiologically active oxygen derivatives (especially hydroxy-, hydroperoxy-, and epoxy compounds) known as the eicosanoids. Their separation into different groups in the so-called A. cascade is shown in the figure... 

Of the long-chain n-3 fatty acids, DHA is important in maintaining normal cerebral cortex and other neuro-related tissues and is essential for functions of the retina. EPA is an eicosanoid precursor, yielding products which reduce platelet aggregation and the risk of arterial thrombosis, among other functions. Stearidonic acid is an essential, but less investigated, intermediary metabolite in the biosynthesis of EPA and DHA in humans. 

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