Membrane essential fatty acids

Evans DR, Parikh W, Khan MM, Coussons C, Buckley PF, et al. 2003. Red blood cell membrane essential fatty acid metabolism in early psychotic patients following... 

Warren G, McKendrick M, Peet M. The role of essential fatty acids in chronic fatigue syndrome a case-controlled study of red-cell membrane essential fatty acids (EFA) and aplacebo-controlled treatment study with high dose of EFA. Acta Neurol Scand 1999 99 112-116. 

Peet, M., Laugharne, J., Rangarajan, N., Horrobin, D. and Reynolds, G. (1995) Depleted red cell membrane essential fatty acids in drug-treated schizophrenic patients. J. Psychiatr. Res. 29 227-232. 

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. 

There are three groups of eicosanoids that are synthesized from C20 eicosanoic acids derived from the essential fatty acids linoleate and a-linolenate, or directly from dietary arachidonate and eicosapentaenoate (Figure 23-5). Arachidonate, usually derived from the 2 position of phospholipids in the plasma membrane by the action of phospholipase Aj (Figure 24-6)—but also from the diet—is the substrate for the synthesis of the PG2, 1X2 series (prostanoids) by the cyclooxygenase pathway, or the LT4 and LX4 series by the lipoxygenase pathway, with the two pathways competing for the arachidonate substrate (Figure 23-5). 

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. 

Hepatic steatosis usually is a result of excessive administration of carbohydrates and/or lipids, but deficiencies of carnitine, choline, and essential fatty acids also may contribute. Hepatic steatosis can be minimized or reversed by avoiding overfeeding, especially from dextrose and lipids.35,38 Carnitine is an important amine that transports long-chain triglycerides into the mitochondria for oxidation, but carnitine deficiency in adults is extremely rare and is mostly a problem in premature infants and patients receiving chronic dialysis. Choline is an essential amine required for synthesis of cell membrane components such as phospholipids. Although a true choline deficiency is rare, preliminary studies of choline supplementation to adult patients PN caused reversal of steatosis. 

There is some evidence that, in these patients, the interconversion between the polyunsaturated fatty acids is disturbed, which restricts the formation of eicosapentaenoic and docosahexaenoic acids. Such children are less likely to have been breastfed (breast milk contains these omega-3 fatty acids) they are more likely to suffer from allergies associated with essential fatty acid deficiency and also dry skin and hair and the membranes of the erythrocytes contain less omega-3 fatty acids compared with normal children. So far, the results of supplementation of the diet of these children with this disorder have not been conclusive. 

Polyunsatmated (essential) fatty acids phospholipids membranes... 

The increased mobilisation of fatty acids from adipose tissue raises the plasma concentration, which increases the rate of fat oxidation by muscle. It also releases some essential fatty acids from the store in the triacylglycerol in adipose tissue. These are required for formation of new membranes in proliferating cells and those involved in repairing the wound (e.g. fibroblasts) (Chapters 11 and 21 Figure 21.22). 

The cycle makes available essential fatty acids that are required for the phospholipid synthesis necessary for new membrane formation in the proliferating tumour cells (Figure 21.22) and for synthesis of eicosanoids for regulation of proliferation. Such factors are also required by proliferating immune ceUs that may attack tumour cells, so that there will be competition for essential fatty acids between immune and tumour cells. 

Fenton, W.S., Hibbeln, J., and Knable, M. (2000) Essential fatty acids, lipid membrane abnormalities, and the diagnosis and treatment of schizophrenia Bio Psychiatry 47 8-21. 

Long-chain fatty acids are hydrophobic substances in plasma they occur in the esterified state or bound to protein (mainly albumin). As a consequence, long-chain fatty acids are not excreted into the urine and are measured either in the plasma or in erythrocytes, where they are part of the membrane. Erythrocyte levels of polyunsaturated fatty acids (PUFA) are fairly constant and may reliably reflect the longterm availability or deficiency of the essential fatty acids. A list of fatty acids that can be separated and analysed by GC is shown in Table 3.3.1. 

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).]... 

Hou, S.Y., et al. 1991. Membrane structures in normal and essential fatty acid-deficient stratum corneum Characterization by ruthenium tetroxide staining and x-ray diffraction. J Invest Dermatol 96 215. 

The biosynthetic pathway of prostaglandins and other eicosanoids is outlined in Figure 15-2. Basically, these compounds are derived from a 20-carbon essential fatty acid. In humans, this fatty acid is usually arachi-donic acid,68,73 which is ingested in the diet and stored as a phospholipid in the cell membrane. Thus, the cell has an abundant and easily accessible supply of this... 

Arachidonic acid (5,8,11,14-eicosatetraenoic acid), a polyunsaturated fatty acid derived from dietary sources or by desaturation and chain elongation of the essential fatty acid linoleic acid, is found widely in the body. It is transported in a protein-bound state and stored in the phospholipids of cell membranes in all tissues of the body [108] from where it can be changed into biologically... 

Alam, S.Q., Alam, B.S., and Ren, Y.F., Adenyl cyclase activity, membrane fluidity and fatty acid composition of rat heart in essential fatty acid deficiency, J. Moll. Cell. Cardiol., 19, 465, 1987. 

Essential fatty acids are precursors to membrane lipids and to compounds that serve as intercellular signals in animals. 

Palmitic acid may be converted to stearic acid (C1K 0) by elongation of the carbon chain. Desaturation of stearic acid produces oleic acid (C18 1 A9). Linoleic acid (Ci8 2A9,12), however, cannot be synthesized in mammalian tissues. Therefore, it is an essential fatty acid for animals and must be obtained from the diet it has two important metabolic roles. One is to maintain the fluid state of membrane lipids, lipoproteins, and storage lipids. The other role is as a precursor of arachidonic acid, which has a specialized role in the formation of prostaglandins (Sec. 13.9). 

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