Fatty Acids and Their Derivatives

School of Pharmacy, University of Oslo, Oslo, Norway 

The biosynthesis of saturated fatty acids has been extensively studied over the years. Already in 1907, Raper reported that fatty acids most likely were derived from a precursor [3]. In 1944, isotopically labeled compounds became available, and Rittenberg and Bloch fed rats with labeled acetate and concluded that fatty acids were indeed synthesized by successive condensation of units. They suspected that the actual metabolic intermediate was an activated form of acetate [4]. Finally, in 1948, Lipmann and 

Kaplan concluded that the activated form of acetate was acetyl-coenzyme A (Ac-CoA) [5]. 

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Natural PPARy Ligands. Endogenous ligands demonstrated to bind and activate PPARy in vitro include unsaturated fatty acids and their derivatives such as prostaglandin J2 (15-deoxy-A12,l4-PGJ2). Consistent... 

Lipids have been dehned on the basis of their stmctnre and solnbility. Lipids are natnrally occnrring componnds consisting of fatty acids and their derivatives, bile acids, pigments, vitamins, and steroids, as well as terpenoids, which are usually soluble in organic solvents such as benzene, chloroform, ether, and alcohol, etc., with variable solubility depending on the stmctnre of the lipid compound. 

HPLC has also been used for analysing fatty acid mixtures [708] and for the characterisation of fatty acids and their derivatives [709]. Fatty acids are commonly analysed on polymeric RPLC columns. Only multiple unsaturated fatty acids can be detected by UV in HPLC the others require derivatisation into UV-absorbing or fluorescing derivatives. Simultaneous determination of saturated and unsaturated fatty acids (C12-C24) by means of RPLC has been reported [710]. Derivatisation is necessary. 

The hydrophobic components of many lipids consist of either isoprenoids or fatty acids and their derivatives 34 Isoprenoids have the unit structure of a five-carbon branched chain 34 Brain fatty acids are long-chain carboxylic acids that may contain one or more double bonds 34... 

FUJII, I., Polyketide biosynthesis in filamentous fungi. In Comprehensive Natural Products Chemistry, Vol. 1, Polyketides and Other Secondary Metabolites Including Fatty Acids and Their Derivatives (U. Sankawa ed.), Elsevier, Amersterdam, 1999, pp. 409-441. 

One could plunge into the steric problems posed by the mechanism of protein synthesis on the ribosome 25 26)> or consider the steric fit of the hormone insulin to its acceptor in the cell membrane 27>. Or one could delve into the beautiful intricacy of terpenoid, squalene and steroid metabolism, or get lost in double bond formation, or in the steric problems posed by the branched chain fatty acids and their derivatives 28-34). 

Fluoroacetate undergoes a "lethal synthesis"(18) to 2-fluorocitrate which may reversibly inhibit aconitase and which irreversibly binds to a membrane-associated citrate transport protein(19,20). Insecticidal and other biocidal uses of fluoroacetate (or its metabolic precursors) received considerable attention twenty-five years ago( ) but most uses have been abandoned due to high nonspecific vertebrate toxicity of these compounds. Vfe have reported the use of o)-fluoro fatty acids and their derivatives as delayed-action toxicants for targeted... 

The plausible deoxygenation routes for production of diesel like hydrocarbons from fatty acids and their derivates are decarboxylation, decarbonylation, hydrogenation and decarbonylation/hydrogenation. The main focus in this study is put on liquid phase decarboxylation and decarbonylation reactions, as depicted in Figure 1. Decarboxylation is carried out via direct removal of the carboxyl group yielding carbon dioxide and a linear paraffinic hydrocarbon, while the decarbonylation reaction yields carbon monoxide, water and a linear olefinic hydrocarbon. 

Inoue, Y. (2001). Recent developments of polyunsaturated fatty acids and their derivatives related research. New Food Industry 43, 22-26 (in Japanese). 

The heterogeneous class of compounds marked by solubility in so-called lipid solvents (acetone, hydrocarbons, ether, etc.) and relative insolubility in water, has traditionally been called lipids (3). This historical classification, based upon isolation procedures from natural products, is obviously too broad for simple generalizations since it includes triglycerides, fatty acids, phospholipids, sterols, sterol esters, bile acids, waxes, hydrocarbons, fatty ethers and hydrocarbons. For the purposes of this chapter, we will consider lipids to be fatty acids and their derivatives. 

Ralston, A. W. Fatty Acids and their derivatives. New York John Wiley 1948. 

Beside the bile salts, the anionic surfactants investigated for enhanced intestinal delivery were mainly sodium salts of fatty acids and their derivatives. These include sodium salts of saturated and unsaturated fatty acids (C8-Ci8), SLS, dioctyl sodium sulfossuccinate (DOSS), and others. 

Mori, S., et al. 2004. Studies on the intestinal absorption of low molecular weight heparin using saturated fatty acids and their derivatives as an absorption enhancer in rats. Biol Pharm Bull 27 418. 

The bulk of our knowledge regarding thermal oxidation has been derived from studies with model systems of fatty acids and their derivatives, or with individual natural oils (2,3,6,12,13,14,15,16). However, in biological systems as complex as food, lipids usually exist in a complicated environment markedly different from that of the single phase model system. In cell membranes, for example, the lipid molecules are highly ordered, relatively restricted in distance and mobility, and closely associated with different neighboring molecules, e.g., other lipids, protein, cholesterol, water, pro- and antioxidants. What influence does such an environment have on the oxidation of the lipids at elevated temperature Even in less organized systems, e.g., depot fat from animal or plant, the lipids... 

Nevertheless, cellulose fatty esters with low DS values show other qualities, such as a high hydrophobicity. The development of water-repellent cellulosic materials (i.e., cotton, wood), has led to interesting applications in the textile and wood industries. For instance, the direct esterification of timber with fatty acids (and their derivatives) has resulted in extraordinary outdoor durability and resistance to biological attack (e.g. rotting, termites). Industrial exploitation of this technology has recently been conducted in France [WoodProtect by Lapeyre (Magne et al., 2003)]. In this case, the water-repellence conferred to wood and the lack of recognition from predator enzymes account for these properties. 

The bases of most functional products possess more-or-less undesirable odor qualities. In creams, soaps, and detergent-based products, it is the greasy or waxy note of fatty acids and their derivatives in cold-wave lotions, depilatories, and insecticides, the pungent smell of active agents in window cleaners and nail polish removers, the sweet "chemical" odor of organic solvents. 

Ralston, A.W. (1948) Fatty Acids and their Derivatives. Wiley, New York. 

Lipids are a complex group of substances, which include the long-chain fatty acids and their derivatives, sterols and steroids, carotenoids, and other related isoprenoids. It is evident that the term lipid denotes a wide range of compounds that appear to have little obvious interrelation. However, although these compounds possess widely different structures, they are derived in part from similar biological precursors and exhibit similar physical and chemical characteristics. Furthermore, most lipids occur naturally in close association with protein, either in membranes as insoluble lipid-protein complexes or as soluble lipoproteins of the plasma. 

Lipids are fatty acids and their derivatives, and substances related biosynthetically or functionally to them. Many fatty acids are still known by their trivial names (e.g., palmitic, linoleic). 

Fatty acids and their derivatives have a place in practically all phases of modern living. They add needed qualities to pharmaceuticals, cosmetics and other personal care products. They improve the performance of paints, lubricants, textiles, detergents and rubber products. 

Ralston, Fatty Acids and Their Derivatives, John Wiley Sons, New York, 1948, p. 474. 

No strict definition exists for the term lipid that is generally accepted. In a broad sense, lipids are compounds of low or intermediate molecular weight with a substantial proportion of hydrocarbons (1). Lipids have also been defined as fatty acids and their derivatives, and substances related biosynthetically or functionally to these compounds (4). Sometimes, it is also expected that molecules considered as lipids have some biological function. Many molecules based on fatty acids are lipids, but some vitamins and hormones are based on fatty acids as well. They serve many functions in living organisms, and the broad scope of these functions is traly fascinating. 

Fatty acids are hydrocarbon chains of various lengths and degrees of unsaturahon that terminate with a carboxylic acid group. The fatty acid chains in membranes usually contain between 14 and 24 carbon atoms they may be saturated or unsaturated. Short chain length and unsaturahon enhance the fluidity of fatty acids and their derivatives by lowering the melting temperature. 

The basic structure, a hydrophobic hydrocarbon chain with a hydrophilic polar group at one end, endows fatty acids and their derivatives with distinctive properties, reflected in both their food and industrial use. Saturated fatty acids have a straight hydrocarbon chain. A trans-Aoablt bond is accommodated with httle change in shape, but a cis bond introduces a pronounced bend in the chain (Fig. 1). 

Although it was initially felt that the free fatty acids acted simply as uncouplers on the mitochondria, this is today considered to be much too simple an explanation. A sketch of the possible interactions of free fatty acids and their derivatives with the mitochondria is shown in Fig. 10.13. Although a series of derivatives are at hand, only extramitochondrial free fatty acids and acyl-CoAs have been more seriously investigated as candidates for the mediator. 

Fig. 10.13. A sketch of the possible interactions of free fatty acids and their derivatives with brown fat mitochondria. The sketch illustrates some of the candidates for the mediator of thermogenesis (i.e., the substance or process that will activate thermogenin (alt. another site of the mitochondrial membrane) even in the presence of the inhibitory cytosohc nucleotides). Common for the candidates shown here is that they are formed subsequent to the activation of lipolysis of the stored triglycerides (TG) by norepinephrine (NE) via cAMP-dependent processes. The candidates illustrated are free fatty acids (FFA), interacting (1) with the purine-nucleotide binding site on thermogenin, (2) with another site on thermogenin, (3) with another protein than thermogenin, or (4) directly with the membrane, and the acyl-CoAs, interacting (5) specifically with the purine-nucleotide binding site on thermogenin, or (6) unspecifically with the membrane. For discussion, see Section 5.

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