Fatty acids, activation essential

Essential fatty acid activity is closely related to double bond structure and to the ability of such acids to be converted into a physiologically active eicosanoid... 

After nearly 60 years of intensive research, we still do not have complete answers to the questions what, in structural terms, determines whether a fatty acid will have essential fatty acid activity why, exactly, are they essential and, how much do we need in the diet In the following sections we shall try to give you a summary of current knowledge. 

This sequence of desaturations and elongations enables tissues to produce a variety of polyunsaturated fatty acids tailored to their needs. Because, during the course of evolution, animals have lost the ability (retained by plants) to insert double bonds in positions 12 and 15, the members of these four families (n-3, n-6, n-7, n-9) cannot be interconverted in animal tissues. Linoleic acid and its relatives are termed essential because without them animals will die. Therefore, the first member of the series has to be supplied in the diet from plant sources. Arachidonic add, the main product of the elongation and desaturation of linoleic acid, has essential fatty acid activity in that it can cure the signs of EFA deficiency described earlier but it is not essential in the human diet as long as linoleic acid is supplied, i.e. it is an essential metabolite but not an essential nutrient for man. 

When the diet contains a small, but normally adequate, amount of linoleic acid which is swamped by enormous amounts of other fatty acids in the diet (e.g. oleic acid or isomeric fatty acids, section 8.15.3). In this situation, the fatty acids in excess compete successfully with linoleic acid for the A6-desaturase and generate a series of polyunsaturated fatty acids that have no essential fatty acid activity and cannot substitute for the linoleic acid family. The effect of this competition is illustrated in Figure... 

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. 

Deficiency of essential amino acid precursors in the diet can cause a dysregulation of neurotransmitter activity (e.g, L-tryptophan deficiency causes a decrease in 5-HT and melatonin synthesis and activity). Deficiency in essential fatty acids (e.g, omega-3 fatty acids) can cause a dysregulation of neurottansmitter... 

Whereas the above evidence clearly points to a catalytic activity of serum albumin, it does not exclude an activity toward less-reactive substrates due to contamination of some HSA preparations. Indeed, the hypothesis of a contamination by plasma cholinesterase (EC 3.1.1.8) has been raised [126][127]. The efficient hydrolysis of nicotinate esters by HSA (see Chapt. 8) [128][129] could be due to contamination by cholinesterase in samples of a commercially available, essentially fatty acid free albumin. Support for this hypothesis was obtained when HSA contaminated with cholinesterase was resolved into two peaks by affinity chromatography, and the esterase activity toward nicotinate esters was found exclusively in the cholinesterase fraction [130],... 

A functional method for detection depends upon competition for the activity of the and desaturases between a non-essential fatty acid (e.g. oleic acid) and an essential fatty acid (see above). If the latter is deficient, oleic acid is readily converted, via the desaturases, to Mead acid, since there is little competition (Figure 11.14). Hence the amount of the latter can be used as a marker for deficiency of essential fatty acids, although it is better to use the ratio of double bonds only three are present in Mead acid (i.e. a triene) but four are present in arachidonic acid (i.e. a tetraene). A ratio in plasma, triene/tetraene >4.0 is an indication of a deficiency of essential fatty acids. This method has shown that a deficiency can occur in a number of conditions which can lead to disease (Table 11.5). 

Human milk is rich in essential fatty acids of both the omega-3 and omega-6 families. This suggests that the activity of the A -desaturase may be too low in the infant to provide a sufficient amount of these fatty acids for development of tissues, particularly the brain and retina. It has been shown that development of visual acuity in infants is dependent upon the presence of docosahexaenoic acid in mother s milk. Hence, it is recommended that breastfeeding should be carried out for as long as 12 months after birth. These fatty acids are now added to commercial infant feeds (Chapter 15, Table 15.8). 

Lipids are important components of the diet fatty acids are the higher energetic source as they ensure 9kcal/g. Furthermore, some peculiar fatty acids themselves and several components of the unsaponifiable fraction are biologically active molecules, as they can act as vitamins (tocopherols— vitamin E), provitamins (carotenes—vitamin A, cholecalcipherol—vitamin D), vitamin-like (essential fatty acids), and hormones or hormone precursors (sterols—steroidal hormones). 

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). 

The carcinogenicity of af la toxin is reduced by protein deficiency, presumably because of reduced metabolic activation to the epoxide intermediate, which may be the ultimate carcinogen, which binds to DNA (Fig. 5.14). A deficiency in dietary fatty acids also decreases the activity of the microsomal enzymes. Thus, ethylmorphine, hexobarbital, and aniline metabolism are decreased, possibly because lipid is required for cytochromes P-450. Thus, a deficiency of essential fatty acids leads to a decline in both cytochromes P-450 levels and activity in vivo. 

The antiscurvy (antiscorbutic) activity was called vitamin C, and when its structure became known it was called ascorbic acid. The fat-soluble factor preventing rickets was designated vitamin D. By 1922, it was recognized that another fat-soluble factor, vitamin E, is essential for full-term pregnancy in the rat. In the early 1930s vitamin K and the essential fatty acids were added to the list of fat-soluble vitamins. Study of the human blood disorders "tropical macrocytic anemia" and "pernicious anemia" led to recognition of two more water-soluble vitamins, folic acid and vitamin B12. The latter is required in minute amounts and was not isolated until 1948. Have all the vitamins been discovered Rats can be reared on an almost completely synthetic diet. However, there is the possibility that for good health humans require some as yet undiscovered compounds in our diet. Furthermore, it is quite likely that we receive some essential nutrients that we cannot synthesize from bacteria in our intestinal tracts. An example may be the pyrroloquinoline quinone (PQQ).e... 

Another possible dietary factor concerns the essential fatty acid content of human and artificial milk. It has been postulated by Sinclair that many modern dietaries are deficient in the essential polyethenoid fatty acids (EFA) and that in consequence there is a rise in unesterified (and more active) vitamin D and in unesterified cholesterol. He has suggested that a part of the etiology of infantile idiopathic hypercalcemia may be attributed to EFA deficiency (S5). He has pointed to the lower content of certain unsaturated fatty acids in cow s milk as compared with human milk as a factor in the development of idiopathic hypercalcemia in artificially fed infants. He considers that dried milk has an even lower content of essential fatty acids than liquid cow s milk and that the longer it is stored the lower does the essential fatty acid content become. On the basis of some observations on rats, he suggests that a dietary deficiency of the essential fatty acids increases susceptibility to the possible toxic effects of vitamin D. The age of the rats, the duration of the essential fatty acid deficient diet, or the dosage of vitamin D is not mentioned, and there would appear to be no other experimental data to support these views. 

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. 

Raghavenra, H., Diwakr, B.T., Lokesh, B.R. and Naidu, K.A. (2006) Eugenol the active principle from cloves inhibits 5-lipoxygenase activity and leukotriene-C4 in human PMNL cells. Prostaglandins, Leukotrienes and Essential Fatty Acids 74, 23-27. 

VI. Van Aswegen, C. H., The effect of essential fatty acids on growth and urokinase-type plasminogen activator production on human prostate DU-145 cells. Prostaglandins Leuk. Essent. Fatty Acids 55, 173-177 (1996). 

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