Hydroxy fatty acids biological activities

Production of Biologically Active Hydroxy Fatty Acids by Pseudomonas aeruginosa PR3... 

Biological activities of hydroxy fatty acids produced by PR3 565... 

PRODUCTION OF BIOLOGICALLY ACTIVE HYDROXY FATTY ACIDS... 

Since Wallen et al. (1962) reported the first bioconversion of oleic acid to 10-hydroxystearic acid by a Pseudomonad, microbial conversions of unsaturated fatty acids from different substrates by various microbial strains have been widely exploited to produce new, value-added products. Among the unsaturated fatty acids used for microbial production of hydroxy fatty acids, three (oleic, linoleic, and linolenic acids) were well studied as substrates to produce mono-, di-, and trihydroxy fatty acids. Recently, a bacterial strain Pseudomonas aeruginosa NRRL B-18602 (PR3) has been studied to produce hydroxy fatty acids from several fatty acid substrates. In this review, we introduce the production of hydroxy fatty acids from their corresponding fatty acid substrates by P. aeruginosa PR3 and their industrially valuable biological activities. 

BIOLOGICAL ACTIVITIES OF HYDROXY FATTY ACIDS PRODUCED BY PR3 565... 

Arachidonic acid released from phospholipids or neutral lipids at sites of inflammation can be converted via the cyclooxygenase system into the biologically active endoperoxide rostaglandin G2 as well as several non-prostanoate hydroxy fatty acids. Alternatively, it may be converted by a lipoxygenase into 2-L-hydroxy-5,8,10-14-eicosatetraneoic a d (HETE). HETE produced by platelet aggregation is chemotactic for PMN (see Chapter 19). 

Because of the increased amounts of omega-6 fatty acids in the Western diet, the eicosanoid metabolic products from AA, specifically prostaglandins, thromboxanes, leukotrienes, hydroxy fatty acids, and hpoxins, are formed in larger quantities than those formed from omega-3 fatty acids, specifically EPA. The eieosanoids from AA are biologically active in very small quantities, and if they are formed in large amounts, they contribute to the formation of thrombus and atheromas to allergic and inflammatory disorders, particularly in susceptible people and to proliferation... 

Hydroxy fatty acids are important industrial materials. These fatty acids are used as raw chemicals in plasticizers, surfactants, and lubricants (1). Some of the known hydroxy fatty acids also have interesting biological activities. Kato et al. (2) and other researchers (3-5) reported that hydroxy fatty acids have antifungal activity. A few hydroxy fatty acids also exhibit cytotoxic activity against cancer cells (6,7) and prostaglandin E-like activity (8). 

It should not be assumed that hydroxy fatty acids are biologically inactive. Hydroxy fatty acids are chemotactic and vasoactive. Such fatty acids could perturb phospholipids in membranes. For instance, cardiolipin containing hydroxy-linoleic acid does not support the electron transport coupled to ATP production of the mitochondrion. 5-Hydroxy de-canoic acid is a well-known inhibitor of the K -ATP channel. Isoprostanes, trihydroxy oxidation products of arachi-donic acid, are vasoconstrictors (76). 13-Hydroxy linoleic acid (13-HODE) is a lipoxygenase-derived metabolite that influences the thromboresistant properties of endothelial cells in culture (77). However, there is some doubt about the tme nature of these hydroxy-fatty acids generated by the cells, as there are several GSH- and NADPH-dependent pathways that can immediately reduce hydroperoxy- to hydroxy-fatty acids. Furthermore, the reduction step of the analytical method would have converted the hydroperoxy- to a hydroxy-group. Nevertheless, much work remains to be done to determine the relative contribution of hydroperoxy- and hydroxy- to the biological effects of fried fat, and in particular their role in endothelial dysfunction and activation of factor VII. There have been earlier suggestions that a diet rich in lipid peroxidation products may lead to atherosclerosis and CHD (34,78). 

LPS with endotoxic properties is not confined to pathogens. Whole cells or cell extracts from commensal organisms often show the same degree of biological activity as similar extracts or killed whole cells from a pathogenic strain. By contrast the potency of lipid A varies with source. Despite the severity of infections caused by them, brucellae and yersiniae possess LPS of relatively low toxicity. Similarly Pseudomonas aeruginosa lipid A is less toxic than that derived from Enterobacteriaceae. This is thought to be a result of the predominance of 12 carbon 3-hydroxy fatty acid substituents... 

Eicosanoids are 20C biologically active compounds which derive from essential fatty acids. Arachidonic acid can be converted to a cyclic endoperoxide and this, in turn, can form prostaglandins, thromboxanes or prostacyclin. In contrast, if arachidonate is acted upon by a lipoxygenase then the leukotrienes or hydroxy fatty acids can be formed. All these eicosanoids have very potent, and often interacting, biological actions and affect almost every tissue in mammals. 

Several pharmacologically active substances are present in superfusates of the cerebral cortex, including acetylcholine, 5-hydroxytryptamine, substance P and the prostaglandins. Members of this latter family of hydroxy-unsaturated fatty acids are released from a great variety of tissues on nerve and hormone stimulation (Ramwell and Shaw 1970), and have been shown to possess a wide range of biological activity (Horton, 1969). 

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