Distribution of Essential Fatty Acids

Drugs of particularly complex structure are often prepared commercially by partial synthesis from some abundant, structurally related, natural product obtained from plants. The majority i)f steroid drugs are in fact prepared in just this way. Prostaglandins are unique in that no prostanoid compounds have yet been found in plants, a perhaps surprising finding in view of the wide distribution of essential fatty acids in plant materials. 

As observed for l- l c -stearic acid, the percentage of labelled "essential fatty acids" incorporated in the triacyiglyceroi fraction from Novikoff hepatoma was significantly depressed when compared with the values for normal liver (Figs. 5 and 6). On the other hand, no significant differences were observed in the percent distribution of "essential fatty acids" into the phospholipid fractions studied. 

Results of chemical analysis showed that the glucosamine and total fatty acid contents of the KDO depleted, toxic lipid A and the nontoxic lipid A were essentially the same but that the nontoxic lipid A was significantly lower in the phosphorus content (Table V). The molar ratio of glucosamine phosphorus fatty acids was 2 2 4 for the toxic lipid A and 2 1 4 for the nontoxic lipid A. The relative molar distribution of normal fatty acids (lauric, myristic, and palmitic acids) and the 3-hydroxymyristic acid did not indicate a correlation between the content of these components and toxicity. The nontoxic lipid A possessed as high a tumor regression activity when combined with CWS as did the purified... 

Progress in understanding the role of the two desaturases has been handicapped by the lack of a reliable purification protocol. Recently, both enzymes have been cloned from mouse and human and shown to share 75% nucleotide homology (Cho et al. 1999ab). Tissue distribution studies revealed that the human A6 desaturase is most abundant in liver and heart, but is present in many tissues, including the brain. By comparison, levels of A5 desaturase mRNA are considerably lower in all tissues examined. Ample evidence indicates that A6- and A5-desaturase expression is nutritionally regulated in a coordinate fashion and is inversely influenced by the quantity of essential fatty acids in the diet. At least in the liver, this occurs at the mRNA level. 

In earlier sections of this chapter we focused on the distribution and physical properties of CE and on several intra- and extracellular enzymes and proteins that mediate CE formation, hydrolysis, and transfer. We turn now to a discussion of the major pathways of CE metabolism in plasma, and in cells such as fibroblasts, steroid hormone-forming cells, macrophages, and hepatocytes. These pathways seem to be integrated in such a way as to effect not only the transport and storage of cholesterol, but possibly also the transport of essential fatty acids. It can be argued in addition that the pathways of CE metabolism in plasma and in tissues provide a critical mechanism for buffering the content of UC in cell membranes and maintaining cholesterol homeostasis in the body (see Chapter 2). 

Propylthiouracil-treated animals also showed a decrease in the percent of linoleic acid distribution in liver. In spite of the results obtained by different authors (Ellefson and Mason, 1964 Mitchel and Truchot, 1962 Kirkeby, 1972), the changes in the percent distribution of total fatty acids in plasma are small and unimportant (Table 3). The probable explanation for the low linoleic acid concentration in liver could be that the supply of essential fatty acids from the diet does not parallel the increase of lipid degradation (Kirkeby, 1972), thereby giving a relative linoleic acid deficiency despite the food intake. The changes on A6 and A9 desaturation activities are not apparently related with the modifications observed in the percent distribution of total fatty acids in liver. This fact could be explained considering that the composition of liver and plasma lipids is a result of a balance between dietary fat, lipid, and carbohydrate metabolism, lipolysis of tissue lipids, and endocrinological factors. 

Mead, J. F. The metabolism of the essential fatty acids. Distribution of unsaturated fatty acids in rats on fat-free and supplemented diets. J. biol. Chem. 227, 1025 (1957). 

For adults, based on the Acceptable Macronutrient Distribution Range, the lOM recommmds a range of 20 to 35% of total calorie intake to be ingested as fat. Low intake of fats may increase the risk of inadequate intakes of essential fatty acids such as linoleic add and a-linolenic acid, and vitamin E. In addition, low-dietary-fat intake may have a potmtial adverse affect on lipid profiles due to increased carbohydrate intake often assodated with low-fat diets. Therefore, the NCEP reconunends a lower limit of 25% for individuals with elevated plasma cholesterol concentrations, established cardiovascular disease, and more than one major risk factor. On the other hand, an upper level intake of total fat, i.e., approximately 35% of total calories, is assodated with increased calorie and saturated fat intake. In individuals with lipid or metabofic disorders, total fat intakes should not be extreme... 

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. 

Triacylglycerols (TAG) are the primary neutral lipids in soybean oil. Due to the high concentration of unsaturated fatty acid in soybean oil, nearly all the TAG molecules contain at least two unsaturated fatty acids, and di- and trisaturates are essentially absent (List el al. 1977). In natural oils and fats, the fatty acids are not usually randomly distributed among the three hydroxyl groups of glycerol but are associated in particular patterns. Several theories of regiospecific distribution exist (Litchfield 1972), but the 1,3-random, 2-random theory is most widely accepted. The stereospecific distribution of fatty acyl groups in soybean oils... 

Clarity at or below ambient room temperature is the primary characteristic of a liquid oil. Natural vegetable oils that are liquid at room temperatures in temperate climates, 75 5°F (23.4 3°C), contain high levels of unsaturated fatty acids with low melting points. Fatty acids with one or more double bonds and 18 carbon atoms are the most important unsaturated fatty acids for liquid oils. Oleic (18 1), a monounsaturated fatty acid, is the most widely distributed and most stable Ci8 unsaturated fatty acid. Linoleic (18 2) and linolenic (18 3) are the most widely distributed di- and triunsaturated fatty acids. Both of these polyunsaturated fatty acids are termed essential because they cannot be synthesized by animals, including man, and must be supplied in the diet. Complete exclusion of the essential fatty acids from the diet results in scaly skin, loss of weight, kidney lesions and eventually death. 

Lipoxygenases (LOX) constitute a family of lipid peroxidizing enzymes, which are distributed widely in the plant and animal kingdoms. These enzymes preferentially metabolize substrates that are polyunsaturated fatty acids containing a series of cis double bonds, which are the essential fatty acids for human beings (Kuhn Thiele, 1999). Lipoxygenases are dioxygenases in nature and... 

The human body can synthesize all except two of the fatty acids it needs. These two, linoleic acid and linolenic acid, are polyunsaturated fatty acids that contain 18 carbon atoms (Table 8.1). Because they are not synthesized within the body and must be obtained from the diet, they are called essential fatty acids. Both are widely distributed in plant and fish oils. In the body, both acids are used to produce hormonelike substances that regulate a wide range of functions and characteristics, including blood pressure, blood clotting, blood lipid levels, the immune response, and the inflammation response to injury and infection. 

Figures 4.10(a) and 4.10(b) show oils from single cells. It is easy to see the difference in chemical shift of the two essential fatty acids, arachidonic acid (ARA) [Fig. 4.10(a)] and 4,7,10,13,16,19-docosahexaenoic acid (DHA) [Fig. 4.10(b)] as well as their asymmetrical distribution.

In an attempt to examine some properties of cancer cells we have measured the ability of Novikoff hepatoma to take up the saturated and "essential fatty acids" from the host and the capacity of this tumoral tissue to distribute these acids between the different lipid fractions. pH -glycerol was also used as a marker for "de novo" glycerolipid biosynthesis. 

Fatty acids that are required by the body but cannot be made in sufficient quantity from other substrates, therefore must be obtained from food and are called essential fatty acids. Essential fatty acids are polyunsaturated fatty acids and are the parent compounds of the omega-6 and omega-3 fatty acid series, respectively. Humans lack the ability to introduce double bonds in fatty acids beyond carbons 9 and 10, Two fatty acids are essential in humans, linoleic acid (LA) and alpha-linolenic acid (ALA). They are widely distributed in plant oils. In addition, fish, flax, and hemp oils contain the longer-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). 

Production by the reaction of a fatty acid with ethylene oxide leads essentially to the monoester with a broad distribution in the molar EO number (n) ... 

---