Essential Fatty Acids and Prostaglandins

The essential fatty acids (EFAs) are essential nutrients which must be provided by the diet because they cannot be synthesized in the body. There are two types of EFAs, the n-6 and n-3, whose parent compounds are linoleic acid and alpha-linolenic acid (ALA), respectively. Linoleic acid and ALA are the main dietary 

Abbreviations used in this chapter ALA, alpha-linolenic acid DGLA, dihomogamma-linolenic acid EFA, essential fatty acid EPA, eicosapentaenoic acid GLA, gamma-linolenic acid 12-HETE, hydroxy-eicosatetraeroic acid PG, prostaglandin NSAID, nonsteroidal anti-inflammatory drug. 

David R Horrobin Scotia Pharmaceuticals, Woodbridge Meadows, Guildford, Surrey GUI IBA, England. 

Subcellular Biochemistry, Volume 25 Ascorbic Acid Biochemistry and Biomedical Cell Biology, edited by J. Robin Harris. Plenum Press, New York, 1996. 

Within the body they are converted by a series of alternating desaturations (which remove two hydrogens) and elongations (which add two carbons). There are 12 EFAs in all, as shown in Fig. 1, which outlines these metabolic pathways. 

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Cunnane SC. 1987. Hepatic triacylglycerol accumulation induced by ethanol and carbon tetrachloride interactions with essential fatty acids and prostaglandins. Alcoholism Clin Exp Res 11 25-31. 

Virkkunen ME, Horroboin DF, Jenkins DK, Manku MS. Plasma phospholipid essential fatty acids and prostaglandins in alcoholic, habitually violent and impulsive offenders. Biol Psychiahy 1987 22 1087-1096. 

Hoeeobin DF (1990) Effects of lithium on essential fatty acid and prostaglandin metabolism. In Bach RO and Gallicchio VS, eds. Lithium and Cell Physiology, pp. 137-149. Springer-Verlag, New York. 

Salfsky B, Wang Y-S, Fusco AC, Antonacci J. The role of essential fatty acids and prostaglandins in cercarial penetration Schistosoma mansoni). J Parasitol 1984 70 656-660. 

Hammarstrom, S. (1983) Leukotrienes. Annual Rev. Biochem., 52, 355-377. Holman, R.T. (ed) (1981) Essential fatty acids and prostaglandins. Progress in Lipid Research, Vol. 20, Pergamon Press, New York. 

Eicosanoids are derived from Cjo (eicosanoic) fatty acids synthesized from the essential fatty acids and comprise important gtoups of physiologically and pharmacologically active compounds, including the prostaglandins, thromboxanes, leukotrienes, and lipoxins. 

Common NSAIDs include aspirin, ibuprofen, indomethacin, naproxen, and ketoprofen. Even though anti-inflammatories generally target cyclooxygenase, there are apparent differences in the details of how they relieve pain. For example, aspirin acts by primarily inhibiting the COX-dependent synthesis of eicosanoids, which are end products of metabolism of essential fatty acids including prostaglandin... 

The benzodioxole ring system is distributed widely in nature and is found in numerous natural products such as safrole and piperonal, as well as a multitude of alkaloids. 1,2-Dioxolanes are intermediates in the arachidonic acid cascade, which is the biochemical pathway from essential fatty acids to prostaglandins and similar hormones. The endoperoxide PGH2 (121) is believed to be formed on initial oxidation of arachidonic acid (120). PGH2 has a half-life of 4-5 minutes and is transformed enzymatically into prostaglandins, prostacyclin and the thromboxanes. These compounds are mediators for the control of platelet aggregation, blood vessel dilation and smooth muscle contraction. 

Linoleic acid and ot-linolenic acid are essential fatty acids and are the important fatty acids involved in the metabolic pathway of prostaglandin synthesis. 

Leng, G.C., Smith, F.B., Fowkes, F.G., Horrobin, D.F., Ells, K., Morse-Fisher, N. and Lowe, G.D. (1994a) Relationship between plasma essential fatty acids and smoking, serum lipids, blood pressure and haemostatic and rheological factors. Prostaglandins Leukot. Essent. Fatty Acids. 51 101-108. 

The eicosanoids—prostaglandins (PGs), thromboxanes (TXs), prostacyclins (PGIs), and leukotrienes (LTs)—are derived from essential fatty acids and act similarly to hormones (Chapter 30). However, they are synthesized in almost all tissues (unlike hormones, which are synthesized in selected tissues) and are not stored to any significant extent their physiological effects on tissues occur near sites of synthesis rather than at a distance. They function as paracrine messengers and are sometimes referred to as autacoids. 

Lipids have considerable economic importance, providing a substantial fraction of calorie intake in North America and Europe. Dietary oo-3 and 00-6 essential fatty acids and their derivatives confer specific physical properties on cell membranes and are necessary for the biosynthesis of prostaglandins. A variety of serious disease states are also known to be related to disorders in... 

Coetzer, H., Claassen, N., van Papendorp, D.H., and Kruger, M.C. (1994) Calcium Transport by Isolated Brush Border and Basolateral Membrane Vesicles Role of Essential Fatty Acid Supplementation, Prostaglandins Leukot. Essent. Fatty Acids 50,251-166. 

DIETARY ESSENTIAL FATTY ACIDS, BRAIN POLYUNSATURATED FATTY ACIDS, AND PROSTAGLANDIN BIOSYNTHESIS... 

Prostaglandins arise from unsaturated C20 carboxylic acids such as arachidonic acid (see Table 26 1) Mammals cannot biosynthesize arachidonic acid directly They obtain Imoleic acid (Table 26 1) from vegetable oils m their diet and extend the car bon chain of Imoleic acid from 18 to 20 carbons while introducing two more double bonds Lmoleic acid is said to be an essential fatty acid, forming part of the dietary requirement of mammals Animals fed on diets that are deficient m Imoleic acid grow poorly and suffer a number of other disorders some of which are reversed on feed mg them vegetable oils rich m Imoleic acid and other polyunsaturated fatty acids One function of these substances is to provide the raw materials for prostaglandin biosynthesis... 

Rats fed a purified nonlipid diet containing vitamins A and D exhibit a reduced growth rate and reproductive deficiency which may be cured by the addition of linoleic, a-linolenic, and arachidonic acids to the diet. These fatty acids are found in high concentrations in vegetable oils (Table 14-2) and in small amounts in animal carcasses. These essential fatty acids are required for prostaglandin, thromboxane, leukotriene, and lipoxin formation (see below), and they also have various other functions which are less well defined. Essential fatty acids are found in the stmctural lipids of the cell, often in the 2 position of phospholipids, and are concerned with the structural integrity of the mitochondrial membrane. 

The role of essential fatty acids in membrane formation is unrelated to prostaglandin formation. Prostaglandins do not reheve symptoms of essential fatty acid deficiency, and an essential fatty acid deficiency is not caused by inhibition of prostaglandin synthesis. 

A. Lupulescu (1996). Prostaglandins, their inhibitors and cancer. Prostaglandins, Leukotrienes and Essential Fatty Acids 54 83-94. 

Prostaglandins (PG s) and leukotrienes (LT s) are biologically active derivatives of 20 carbon atom polyunsaturated essential fatty acids, which contains 3, 4 or 5 double bonds (e.g. 5,8,11,14-eicosatetraenoic acid i.e., arachidonic acid). 

Bordia, A., S. K. Verma, and . C. Srivastava. 1997. Effect of ginger (Zingiber officinale Rose.) and fenugreek (Trigonellafoenumgraecum L.) on blood lipids, blood sugar and platelet aggregation in patients with coronary artery diseases. Prostaglandins Leukotrienes Essential Fatty Acids 56 379-384. 

The dietary precursor of the prostaglandins is the essential fatty acid, linoleic acid. It is elongated and desaturated to arachidonic acid, the immediate precursor of the predominant class of prostaglandins (those with two double bonds) in humans (Figure 17.22). [Note Arachidonic acid is released from membrane-bound phospholipids by phospholipase Ap in response to a variety of signals (Figure 17.23).]... 

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