Fatty acid conjugates alcohols

The mechanism by which xenobiotic alcohols or esters are converted to fatty acid esters has not been studied. They could be formed by the action of lyase enzymes in the presence of fatty acid glyceryl esters, as in the conversion of farnesol to farnesol fatty acid esters (150). Some lipolytic acyl hydrolase enzymes from plants readily catalyze the transfer of lipid-bound fatty acids to low MW alcohol acceptors (150.151) and enzymes of this class could be responsible for the occasional formation of fatty acid conjugates of xenobiotic alcohols. Mechanisms involving fatty acid acyl CoA, phospholipids, or direct esterification with fatty acids might also be involved (1 ). 

Fatty acyls FA Fatty acids and conjugates Octadecanoids Eicosanoids Docosanoids Fatty alcohols Fatty aldehydes Fatty esters 0 Fatty acid palmitic acid... 

Because of the ketone group on every other carbon atom in the growing chain, these compounds are known collectively as polyketides. To make a saturated fatty acid, the ketone needs to be selectively reduced to an alcohol, water needs to be eliminated, and the conjugated double bond reduced. All these steps have simple chemical analogies. 

Some metabolic conjugative processes result in the production of lipophilic derivatives that are not readily eliminated. While their physical properties are different from the classical hydrophilic conjugates, the mechanism of formation clearly defines them as conjugates (i.e., they are formed as the result of a union of xenobiotic metabolites with endogenous molecules). The reactions involve the coupling of xenobiotic acids and alcohols with endogenous intermediates of lipid synthesis (i. e., the acids with glycerol and cholesterol and the alcohols with the fatty acids). 

Figure 10.1 Examples of structural formulas of phytosterol and sterol conjugates. FS = free sterol alcohol, SE = sterol fatty acid ester, SF = steryl ferulate, SG = steryl glycoside, ASG = acylated steryl glycoside.

For example, when CH3CH2OH (ethanol) is ingested, it is oxidized in the liver first to CH3CHO (acetaldehyde), and then to CH3COO (acetate anion, the conjugate base of acetic acid). Acetate is the starting material for the synthesis of fatty acids and cholesterol. Both oxidations are catalyzed by the enzyme alcohol dehydrogenase. 

Fatty acids are activated on the outer mitochondrial membrane, whereas they are oxidized in the mitochondrial matrix. A special transport mechanism is needed to carry long-chain acyl CoA molecules across the inner mitochondrial membrane. Activated long-chain fatty acids are transported across the membrane by conjugating them to carnitine, a zwitterionic alcohol. The acyl group is transferred from the sulfur atom of CoA to the hydroxyl group of carnitine to form acyl carnitine. This reaction is catalyzed by carnitine acyltransferase I (also called carnitine palmitoyl transferase I), which is bound to the outer mitochondrial membrane. 

Mechanistic studies of autoxidation have concentrated on methylene-interrupted fatty acids, but many of the observations are valid for other compounds. Conjugated fatty acids such as CLA also oxidize through an autocatalytic free radical reaction, with the predominant hydroperoxide determined by the geometry of the conjugated diene system (45). Other groups with activated methylenes may be susceptible to oxidation, for example, the ether methylenes of ethoxylated alcohols used as surfactants (46). 

Certain xenobiotic alcohols and amines react with natural fatty acids to form nonpolar conjugates. Hany of the early Investigations In this area were conducted by Edith Lelghty and her coworkers who found fatty acid derivatives of the following DDOH, a DDT metabolite ( ) several tetrahydrocannablnols (25,26, also cf. cyclohexylamlne, from cyclamate ( ) codeine (29) trl-... 

Another potential area of application of FTIR spectroscopy is in the determination of the oxidative status or stability of an oil. Autoxidation is a major deteriorative reaction affecting edible fats and oils, and it is of major concern to processors and consumers from the standpoint of oil quality, as the oxidative breakdown products cause marked off flavours in an oil. A wide range of end products are associated with the autoxidative deterioration of fats and oils, the most important being hydroperoxides, alcohols, and aldehydes. Moisture, hydrocarbons, free fatty acids and esters, ketones, lactones, furans, and other minor products may also be produced, with the free fatty acids becoming more important in thermally stressed oils. In addition, there is significant cis to trans isomerisation and conjugation of double bonds in the hydroperoxides formed as an oil oxidises. 

A very different type of reaction is represented by the conjugation of xenobiotic alcohols with fatty acids, yielding highly lipophilic metabolites accumulating in tissues. Thus, ethanol and haloethanols form esters with palmitic acid, oleic acid, linoleic acid, and lin-olenic acid enzymes catalyzing such reactions are cholesteryl ester synthase (EC 3.1.1.13) and fatty-acyl-ethyl-ester synthase (EC 3.1.1.67) (71). Larger xenobiotics such as tet-rahydrocannabinols and codeine are also acy-... 

Tall oils are obtained in large quantity from the pulping of soft -woods to make paper. Hoyt and Goheen ( l) state that in 196U the yield of fatty and rosin acids exceeded 1 00,000 tons. Tall oil contains about 9b% total acids and 6% alcohols. The fatty acid fraction contains oleic v 2k% and linoleic v 23%, of which V b°fo is conjugated linoleic of the tall oil. The rosin acid fraction contains abietic acid lk%> and related acids 33 of the total (,2). An extensive literature on general aspects of the colloidal chemistry of compounds in this class is available (see, for example, references 3, 5, and 6 ). 

Reduction proceeds smoothly with fatty acid esters, but not with aromatic esters whose carboxylic ester group is attached directly to a benzene ring., / -Unsaturated esters give the related saturated alcohols, but double bonds that are not conjugated to the alkoxycarbonyl group are, in general, not reduced by this method. 

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