Fatty acids derivatives

Most fatty acids are carboxylic acids with an unbranched, even numbered carbon chain. They may be saturated or may contain one or more double bonds which usually have the cis-configuration. In the polyunsaturated compounds the double bonds are separated by methylene groups (Table 26). 

The following shorthand designation may be used to describe the chemical structure of fatty acids the number of carbon atoms in the chain separated by a colon from the number of unsaturated bonds is followed by a set of parentheses containing the numbers of the double-bond positions and the letters c, t, or a to indicate whether a bond is cis-olefinic, trans-olefinic, or acetylenic. The position of double bonds is numbered from the carboxyl group. 

Fatty acids are built from acetyl CoA as a starter and several molecules of malo-nyl CoA (D 3) by fatty acid synthase, as is shown schematically in Fig. 52. In yeast the enzymes involved are located on two polyfunctional proteins. It is still unclear whether similar polyfunctional enzymes exist in other organisms. 

Synthesis of fatty acids begins with the linkage of acetyl CoA (or another acyl CoA), to the SH-group of a peripheral subunit of the enzyme protein with elimination of the CoA residue. Simultaneously a molecule of malonyl CoA is bound to another domain, the acyl carrier (ACP), again with the loss of CoA. The malonyl residue becomes attached to the SH-group of a 4-phospho- 

Reduction of the ACP-bound acetoacetate yields D-jff-hydroxybutyryl-ACP from which croto-nyl-ACP is formed by the elimination of water. By the subsequent reduction butyryl-ACP is obtained from which the butyryl residue is transferred to CoA, releasing the SH-group of panto-theine which again reacts with a molecule of malonyl CoA. Butyryl CoA, like acetyl CoA, may react with the peripheral, acyl-binding SH-group of the synthase and subsequently with the malonyl residue. In the following reactions caproic acid is formed from which caprylic, capric, lauric, myristic, palmitic, stearic, and arachidonic acid (Table 26) are formed. The specificity of the enzymes involved as well as other factors such as compartmentalization, stop chain elongation at about 10-20 C-atoms. 

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Fatty acids occur naturally m forms other than as glyceryl triesters and we 11 see numerous examples as we go through the chapter One recently discovered fatty acid derivative is anandamide... 

Fatty acids normally occur naturally as esters fats oils phospholipids and waxes all are unique types of fatty acid esters There is however an important class of fatty acid derivatives that exists and carries out its biological role m the form of the free acid This class of fatty acid derivatives is described m the following section... 

Fatty acids derived from animal and vegetable sources generally contain an even number of carbon atoms siace they are biochemically derived by condensation of two carbon units through acetyl or malonyl coenzyme A. However, odd-numbered and branched fatty acid chains are observed ia small concentrations ia natural triglycerides, particularly mminant animal fats through propionyl and methylmalonyl coenzyme respectively. The glycerol backbone is derived by biospeciftc reduction of dihydroxyacetone. 

Although in the dry state carbon tetrachloride may be stored indefinitely in contact with some metal surfaces, its decomposition upon contact with water or on heating in air makes it desirable, if not always necessary, to add a smaH quantity of stabHizer to the commercial product. A number of compounds have been claimed to be effective stabHizers for carbon tetrachloride, eg, alkyl cyanamides such as diethyl cyanamide (39), 0.34—1% diphenylamine (40), ethyl acetate to protect copper (41), up to 1% ethyl cyanide (42), fatty acid derivatives to protect aluminum (43), hexamethylenetetramine (44), resins and amines (45), thiocarbamide (46), and a ureide, ie, guanidine (47). 

The typical alkyd resin (see above) is eomprised of three basic components an aromatic diacid such as phthalic anhydride which together with a polyol such as glycerol, forms the backbone of the resin molecule and along which are distributed the fatty acids derived from vegetable oils. The solubility, film hardness and colour of alkyd resins depend on the nature of the modifying fatty acid which in most cases contributes some colour to the film. 

Most of the inhibitors in use are organic nitrogen compounds and these have been classified by Bregman as (a) aliphatic fatty acid derivatives, b) imidazolines, (c) quaternaries, (d) rosin derivatives (complex amine mixtures based on abietic acid) all of these will tend to have long-chain hydrocarbons, e.g. CigH, as part of the structure, (e) petroleum sulphonic acid salts of long-chain diamines (preferred to the diamines), (/) other salts of diamines and (g) fatty amides of aliphatic diamines. Actual compounds in use in classes (a) to d) include oleic and naphthenic acid salts of n-tallowpropylenediamine diamines RNH(CH2) NH2 in which R is a carbon chain of 8-22 atoms and x = 2-10 and reaction products of diamines with acids from the partial oxidation of liquid hydrocarbons. Attention has also been drawn to polyethoxylated compounds in which the water solubility can be controlled by the amount of ethylene oxide added to the molecule. 

PPARa Liver, heart, skeletal muscle, atherosclerotic lesions TG- and LDL-C-lowering and HDL-C-raising re-directs excess cholesterol from the peripheral tissues to the liver for excretion into the bile via HDL-C slowed progression of atherosclerosis Fatty acids, eico-sanoids (fatty acids derived from FAS ) Fibrates fenofibrate (Tricor ), genfibrozil (Lopid ) Dyslipidemia... 

PPAR5 Ubiquitous Potent TG- and LDL-C-lowering and potent HDL-C-raising increased oxidative disposal of fatty acids in adipose and skeletal muscle thermogenesis weight loss Fatty acids, eicosanoids (fatty acids derived from VLDL particles ) GW501516 currently in Phase II clinical trials Dyslipidemia, obesity atherosclerosis ... 

NOTE To further confuse matters, PEGS dioleate is also known as PEG 400 dioleate. Similarly, PEGS is also known as PEG 200, and PEGS is also known as PEG 300, etc. These various PEGs are available as cocoamides, dicoates, dilaurates, distearates, ditallates, and other fatty acid derivatives. 

The manner in which salicylates relieve pain and reduce inflammation is not fully understood. It is thought that the analgesic action of the salicylates is due to tiie inhibition of prostaglandins. Prostaglandins are fatty acid derivatives found in almost every tissue of the body and body fluid. Release of prostaglandin is thought... 

Based on ether carboxylic acids it is possible in principle to make the same derivatives as with fatty acids, such as esters, amides, and acid chlorides. The hydrophilic chain in the molecule may confer special properties in comparison with the fatty acid derivatives. 

Primary alcohols are produced either by the catalytic hydrogenation of methyl esters or by fatty acids derived from oils and fats, e.g., coconut oil (C12-C14) or tallow (Cl6-C18), or from synthetic sources. Alcohols manufactured from natural oils and fats and from the Ziegler-type processes produce even-numbered chain length primary alcohols. 

Scheme 9.12 Soybean lipoxygenase (SBLO)-mediated oxygenation of fatty acid derivatives.

Assist the widely dissimilar ingredients used in a rubber compound to coalesce and mix into a homogeneous uniform processable mass. Homogenisers are low-MW polymeric resin blends. The homogenising resin blend contains portions that are compatible with aliphatic, naphthenic and aromatic parts of the elastomers in a blend and higher-MW homologues of the plasticisers. They have a wetting effect. Fatty acid derivatives and phenolic resins are used. 

In addition to anandamide, several other endogenous polyunsaturated fatty acid derivatives were also found to act as cannabimimetics. They are all now collectively referred to as endocannabinoids. Soon after the discovery of anandamide, two more fatty acid ethanolamides were isolated and found to bind to CB1 preparations with affinities similar to that of anandamide (anandamide CB1 binding affinity K = 39.2 nM, according to Hanus et al., 1993). These were the homo-y-linolenylethanol-amide (CB1 K[ = 53.4 nM) and 7,10,13,16-docosatetraenylethanolamide (CB1 K[ = 34.4 nM) (Fig. 2). All three V-acylethanolamide endocannabinoids were found to be CB1 agonists in the MVD test (Pertwee, 1994). 

Di Marzo V, Bisogno T, De Petrocellis L, Melck D, Martin BR. Canna-bimimetic fatty acid derivatives anandamide family and other endocan-nabinoids. Curr Med Chem 1999b 6 721-744. 

Examples of internal lubricants are fatty acid derivatives, e.g., stearates (for PVC), waxes and polyethylene oligomers containing polar groups obtained by partial oxidation. Not all polymers require lubricants LDPE, nylon and PET are self-lubricating. 

Finally, an intriguing possible future therapy arises from a radical idea of Horrobin (2001) that schizophrenia is a nutritional disorder linked to a decreased intake of essential polyunsaturated fatty acids. Recent 31P-MRS studies have shown changes in plasma membrane phospholipids in the neocortex of unmedicated schizophrenics, which would have deleterious consequences on synaptic neurotransmission (Fukuzako, 2001). A clinical trial with the co6 fatty acid derivative ethyleicosa-pentaenoic acid (LAX-101) in patients who had been unresponsive to clozapine, reported that a daily dose of 2g LAX-101 gave a 26% improvement in symptoms over 12 weeks compared with 6% with placebo (Peet and Horrobin, 2001). Maybe in... 

Plants were probably the first to have polyester outerwear, as the aerial parts of higher plants are covered with a cuticle whose structural component is a polyester called cutin. Even plants that live under water in the oceans, such as Zoestra marina, are covered with cutin. This lipid-derived polyester covering is unique to plants, as animals use carbohydrate or protein polymers as their outer covering. Cutin, the insoluble cuticular polymer of plants, is composed of inter-esterified hydroxy and hydroxy epoxy fatty acids derived from the common cellular fatty acids and is attached to the outer epidermal layer of cells by a pectinaceous layer (Fig. 1). The insoluble polymer is embedded in a complex mixture of soluble lipids collectively called waxes [1], Electron microscopic examination of the cuticle usually shows an amorphous appearance but in some plants the cuticle has a lamellar appearance (Fig. 2). 

Oxylipin is a term that has not yet fully entered the scientific vocabulary. Indeed, a new word for oxidized fatty acid-derived compounds was needed, as the older terms - prostanoids, eicos-anoids - proved to be too narrow for an ever-widening spectrum of discoveries. Much of this research has come from the laboratory of the authors of Chapter 4. Their account demonstrates the... 

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