Eicosanoid hormones, production

Outline of pathways for the biosynthesis of major cellular lipids (other than cholesterol) in a mammalian cell. Most of the metabolism of these lipids occurs on membrane surfaces because of the insoluble nature of the substrates and products. These lipids play three major roles (l) they act as a storehouse of chemical energy, as with triacylglycerols (2) they are structural components of membranes (boxed compounds) and (3) they act as regulatory compounds (underlined), either as eicosanoids, which act as local hormones, or as phosphorylated inositols and diacylglycerols, which function as second messengers. 

In animals hormones are either formed de novo from substances of primary metabolism, e.g., steroid hormones, epinephrine, tyroxin, or they are synthesized from special secondary products which have to be taken up with the diet, e.g., unsaturated fatty acids (vitamins F) which are precursors of the eicosanoids. 

Arachidonic (all ds 5,8,11,14-eicosatetraenoic) acid has been shown to have equivalent or even greater activity than linoleic add, and linolenic (all d59,12,15-octadecadienoic) acid is about 1.5 times as effective as linoleic acid. Mammals cannot synthesise fatty acids with double bonds closer than carbon atom 9 from the terminal methyl group. Such acids have to be supplied in the diet. Linoleic add (18 2n-6) and a-linolenic acid (18 3 n-3) are thus dietary essentials. Arachidonic acid is synthesised in the body from linoleic acid. However, one of the steps in the synthesis, a A-6 desaturation, is rate-limiting and production may be slow and an exogenous supply advantageous (see Box 3.1). Linoleic and a-linolenic acids are referred to as the essential fatty acids (ERA). Like other polyunsaturated acids, they form part of various membranes and play a part in hpid transport and certain lipoprotein enzymes. In addition, they are the source materials for the synthesis of the eicosanoids. These include the prostaglandins, thromboxanes and leukotrienes, hormone-like substances that regulate... 

The site-selective epoxidation of polynnsatnrated substrates is a key process in the biosynthesis of several families of natural products, including steroids and triterpenoids (from 2,3-(S)-oxidosqualene), insect jnvenile hormones (famesoate or homofamesoate terminal epoxides), and eicosanoids (e.g., leukotriene-A or (ll/ ,12S)-oxidoarachidonic acid). Corey s group has developed an effective strategy for the efficient site-selective epoxidation of polyolefinic isoprenoid alcohols based on the use of an internal control element for intramolecular reaction (Scheme 9.43) [56]. This approach is illustrated by its application to a series of polyisoprenoid alcohols (poly-prenoids) at substrate concentration of 0.5 mM. Polyprenol substrates, which are having a phenol functionality at one terminus, can direct selective internal epoxidation at a double bond, which is positioned either four or five prenyl units away from the hydroxyphenyl terminal. 

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