Platelet fatty acids

Conflicting results have been reported about the absorption of EPA and DHA either as an ethyl ester (EE) or in a triglyceride (TG) formula. Based on a randomized double-blind study on the effects of EE and TG on plasma fatty acids, platelet function and haemostasis, it has been concluded that TG and EE fish oils are well incorporated... 

Seiss W, Scherer B, Bohlig B, Roth P, Kurzman L and Weber PC. (1980). Platelet-membrane fatty acids, platelet aggregation, and thromboxane formation during Mackrel diet Lancet 1,441-444. 

Each component of blood has a function ia the body. Red cells transport oxygen and carbon dioxide between the lungs and cells ia the tissues. White cells function as defense of the body. Platelets are important for hemostasis, ie, the maintenance of vascular iategrity. Plasma, an aqueous solution containing various proteias and fatty acids, transports cells, food, and hormones throughout the body. Some proteias ia plasma play a role ia clotting, others are messengers between cells. 

Animal cells can modify arachidonic acid and other polyunsaturated fatty acids, in processes often involving cyclization and oxygenation, to produce so-called local hormones that (1) exert their effects at very low concentrations and (2) usually act near their sites of synthesis. These substances include the prostaglandins (PG) (Figure 25.27) as well as thromboxanes (Tx), leukotrienes, and other hydroxyeicosanoic acids. Thromboxanes, discovered in blood platelets (thrombocytes), are cyclic ethers (TxBg is actually a hemiacetal see Figure 25.27) with a hydroxyl group at C-15. 

CYP5 synthesizes thromboxane A2, a fatty acid in the arachidonic acid cascade that causes platelet aggregation. Aspirin prevents platelet aggregation because it blocks the cyclooxygenases COX1 and COX2 which catalyze the initial step of the biotransformation of arachidonic acid to thromboxane and prostaglandins. 

An excellent example of PLC applications in the indirect coupling version is provided by the works of Miwa et al. [12]. These researchers separated eight phospholipid standards and platelet phospholipids from the other lipids on a silica gel plate. The mobile phase was composed of methylacetate-propanol-chloro-form-methanol-0.2% (w/v) potassium chloride (25 30 20 10 10, v/v). After detection with iodine vapor (Figure 9.2), each phospholipid class was scraped off and extracted with 5 ml of methanol. The solvent was removed under a stream of nitrogen, and the fatty acids of each phospholipid class were analyzed (as their hydrazides) by HPLC. The aim of this study was to establish a standardized... 

Lipoxygenases catalyse the regio-specific and stereoselective oxygenation of unsaturated fatty acids. The mammalian enzymes have been detected in human platelets, lung, kidney, testes and white blood cells. The leukotrienes, derived from the enzymatic action of the enzyme on arachidonic acid, have effects on neutrophil migration and aggregation, release of lysosomal enzymes, capillary permeability, induction of pain and smooth muscle contraction (Salmon, 1986). 

Omega-3 fatty acids (eicosapentaenoic acid and docosa-hexaenoic acid), the predominant fatty acids in the oil of cold-water fish, lower triglycerides by as much as 35% when taken in large amounts. Fish oil supplements may be useful for patients with high triglycerides despite diet, alcohol restriction, and fibrate therapy. This effect may be modulated thru PPAR-a and a reduction in apolipoprotein B-100 secretion. Omega-3 fatty acids reduce platelet aggregation and have... 

Bazan, N. G. Synaptic lipid signaling significance of polyunsaturated fatty acids and platelet-activating factor. /. Lipid Res. 44 2221-2233, 2003. 

Panetta, T., MarcheselH, V. L., Braquet, P., Spinnewyn, B. and Bazan, N. G. Effects of a platelet-activating factor antagonist (BN52021) on free fatty acids, diacylglycerols, polyphosphoinositides and blood flow in the gerbil brain Inhibition of ischemia-reperfusion induced cerebral injury. Biochem. Biophys. Res. Commun. 149 580-587,1987. 

Unlike iNOS and nNOS, the eNOS protein is post-translationally modified by the attachment of fatty acids, myristate or palmitate. This modification is important because the fatty acids help to attach the enzyme, in an inactive form, to the inner face of plasma membrane of endothelial cells or platelets. Several mechanisms serve to release eNOS from its membrane bound state and thus activate the enzyme. 

Esterases play a role in regulating the platelet-activating factor (PAF), a lipid with hypotensive properties [96], Phospholipase A2 (EC 3.1.1.4) is involved in this pathway by hydrolyzing a precursor to lyso-PAF and a free fatty acid. The activity of PAF, formed by acetylation of lyso-PAF, is controlled by an esterase hydrolyzing the acetate moiety [100]. 

Srivastava KC. (1989). Effect of onion and ginger consumption on platelet thromboxane production in humans. Prostaglandins Leukot Essent Fatty Acids. 35(3) 183-5. 

The plasma level of fatty acids in a fed subject is between 0.3 and 0.5 mmol/L. As discussed above, the maximal safe level is about 2 mmol/L. This is not usually exceeded in any physiological condition since, above this concentration, that of the free (not complexed with albumin) fatty acids in the blood increases markedly. This can then lead to the formation of fatty acid micelles which can damage cell membranes the damage can cause aggregation of platelets and interfere with electrical conduction in heart muscle (Chapter 22). The cells particularly at risk are the endothelial cells of arteries and arterioles, since they are directly exposed to the micelles, possibly for long periods of time. Two important roles of endothelial cells are control of the diameter of arterioles of the vascular system and control of blood clotting (Chapter 22). Damage to endothelial cells could be sufficiently severe to interfere with these functions i.e. the arterioles could constrict, and the risk of thrombosis increases. Both of these could contribute to the development of a heart attack (Chapter 22) (Box 7.4). 

Figure 22.6 How various factors increase the risk of atherosclerosis, thrombosis and myocardial infarction. The diagram provides suggestions as to how various factors increase the risk of development of the trio of cardiovascular problems. The factors include an excessive intake of total fat, which increases activity of clotting factors, especially factor VIII an excessive intake of saturated or trans fatty acids that change the structure of the plasma membrane of cells, such as endothelial cells, which increases the risk of platelet aggregation or susceptibility of the membrane to injury excessive intake of salt - which increases blood pressure, as does smoking and low physical activity a high intake of fat or cholesterol or a low intake of antioxidants, vitamin 6 2 and folic acid, which can lead either to direct chemical damage (e.g. oxidation) to the structure of LDL or an increase in the serum level of LDL, which also increases the risk of chemical damage to LDL. A low intake of folate and vitamin B12 also decreases metabolism of homocysteine, so that the plasma concentration increases, which can damage the endothelial membrane due to formation of thiolactone.

CN125 Vas Dias, F. W., M. J. Gibney, and T. G. Taylor. The effect of polyunsatu-rated fatty acids on the n-3 and n-6 series on platelet aggregation and platelet and aortic fatty acid composi-tion in rabbits. Atherosclerosis 1982 43(2-3) 245-257. 

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