18-Carbon PUFAs

Significance of 18-Carbon PUFA in the Epidermis Generation of Biologically Active Monohydroxy Fatty Acids... 

Elovl-2 (formerly denoted as Ssc2) is involved in the biosynthesis of the n - 3 and n - 6 series of highly unsaturated fatty acids (HUFA). Expression studies in yeast demonstrated that Elovl-2 is able to efficiently elongate 20- and 22-carbon PUFA but is unable to elongate 18-carbon SFA, MUFA, and PUFA. Elovl-2 is predominantly expressed in the testis, a tissue in which HUFA are synthesized in high levels (A. Leonard, 2(X)2). 

The three major families of unsaturated fatty acids are those of oleic acid (n-9), linoleic acid (n-6) and hnolenic acid (n-3). Linoleic and linolenic acid, the 18-carbon essential fatty acids obtained from the diet, are converted through desaturation and elongation steps to the long-chain polyunsaturated fatty adds (PUFAs). The 20-carbon PUFAs, dihomogammalinoleni acid (DHGLA 20 3 n-6), arachidonic acid (AA 20 4 n-6) and eicosapentaenoic acid (EPA 20 5 n-3), derived from linolenic acid, are the precursors of the prostaglandin series 1,2 and 3, respectively. 

One of the key functional roles of PUFA is as precursors to eicosanoids. Eicosanoids are a family of bioactive mediators that are oxygenated derivatives of the 20-carbon PUFA dihomo-y-linolenic, arachidonic and eicosapentaenoic acids. Eicosanoids include prostaglandins (PG) and thromboxanes (TX), which together are termed prostanoids, and leukotrienes (LT), lipoxins (LX), hydroperoxyeicosatetraenoic acids (HPETE) and hydroxyeicosatetraenoic acids (HETE). In most conditions the principal precursor for these compounds is arachidonic acid, and the eicosanoids produced from arachidonic acid sometimes have more potent biological functions than those released from dihomo-y-linolenic or eicosapentaenoic acids. The precursor PUFA is released from membrane diacylglycerophospholipids by the action of phospholipase A or from membrane phosphatidylinositol-4,5-bisphosphate by the actions of phospholipase C and a diacylglycerol (DAG) lipase (Figure 7). 

The liver is responsible for the conversion of ALA into EPA and DHA via a series of elongation and desaturation steps. The A5 and A6 desaturases are important enzymes in the biosynthesis of 20 carbon PUFAs. However, very little is known about the ability of the body to convert large amounts of ALA to its long-chain derivatives (Morise et al., 2004). Impairment in the A5 and A6 desatu-rase index is associated with NAFLD (Burdge et al., 2002 Allard et al., 2008). A reduction in A5 desaturase activity is also associated with IR (reviewed by Vessby, 2000) and obesity (Pan et al., 1994). It is important to determine if dietary ALA can elevate EPA and DHA in hepatic TAG and PL by increasing A5 and A6 desaturase activity. This suggests a possible mechanism for improved hepatic steatosis, IR and obesity. 

Second-derivative spectrophotometry has been used to monitor the time-dependent production of cis,tmns-(Xmax 242 nm) and trans, tram- (Xmax 232 nm) diene conjugates of microsomal PUFAs following the exposure of rats to carbon tetrachloride (CCU) (Corongui et al., 1986). These signals have been postulated to be derived from mixtures of peroxidized substrates. Previous studies using chemical model systems have established that autoxidation of linolenic or arachidonic acid results in the production of cis, trans- and tmns, trawr-conjugated diene... 

The identification and quantification of potentially cytotoxic carbonyl compounds (e.g. aldehydes such as pentanal, hexanal, traw-2-octenal and 4-hydroxy-/mAW-2-nonenal, and ketones such as propan- and hexan-2-ones) also serves as a useful marker of the oxidative deterioration of PUFAs in isolated biological samples and chemical model systems. One method developed utilizes HPLC coupled with spectrophotometric detection and involves precolumn derivatization of peroxidized PUFA-derived aldehydes and alternative carbonyl compounds with 2,4-DNPH followed by separation of the resulting chromophoric 2,4-dinitrophenylhydrazones on a reversed-phase column and spectrophotometric detection at a wavelength of378 nm. This method has a relatively high level of sensitivity, and has been successfully applied to the analysis of such products in rat hepatocytes and rat liver microsomal suspensions stimulated with carbon tetrachloride or ADP-iron complexes (Poli etui., 1985). 

Lipid peroxidation is a radical-mediated chain reaction resulting in the degradation of polyunsaturated fatty acids (PUFAs) that contain more than two covalent carbon-carbon double bonds (reviewed by Esterbauer et al., 1992). One of the major carriers of plasma lipids is LDL, a spherical molecule with a molecular weight of 2.5x10 . A single LDL particle contains 1300 PUFA molecules (2700 total fatty-acid molecules) and is... 

Escolar and oilfish contain a mixture of wax esters with different carbon-chain length, mainly C32, C34, C36, and C38, formed by combining different fatty acids and fatty alcohols. The dominant fatty acids in escolar and oilfish wax esters are the monounsaturated fatty acids (Table 1.3), namely oleic acid (18 1 oo9) and eicosenoic acid (20 loo9), while the dominant fatty alcohols are saturated and monoenoic fatty alcohols (Table 1.4), known as cetyl alcohol (16 0) and oleyl alcohol (18 1 9). PUFA, which are trace components in muscle wax esters, are commonly found in wax esters from roe, they include 20 4o)6, 20 5(b3, 22 5cd3 and 22 6 3. These differences could be due to the functional role in muscle for providing buoyancy, while that of roe is to store energy and key essential PUFA for fry development (Lee and Patton, 1989). 

Enzymes present in the ER are responsible for desaturating fatlyj j acids (that is, adding cis double bonds). Termed mixed-function oxidases, the desaturation reactions require NADPH and 02. A van-l ety of polyunsaturated fatty acids (PUFA) can be made through addi-l tional desaturation combined with elongation. [Note Humans laal the ability to introduce double bonds between carbon 9 and the col... 

E9 10. Polyunsaturated fatty acids (PUFAs) have several carbon-carbon double bonds as present in /3-carotene. Why are PUFAs not colored like fi-carotene ... 

About 40 different fatty acids occur naturally. Palmitic acid (Ci6) and stearic acid (Cis) are the most abundant saturated acids oleic and linoleic acids (both G ) are the most abundant unsaturated ones. Oleic acid is monounsaturated because it has only one double bond, but linoleic and linolenic acids are polyunsaturated fatty acids (called PUFAs) because they have more than one carbon-carbon double bond. Although the reasons are not yet clear, it appears that a diet rich in saturated fats leads to a higher level of blood cholesterol and consequent higher risk of heart attack than a diet rich in unsaturated fats. 

Three major families of unsaturated fatty acids are seen in warm-blooded animals, that is, the n-9, monounsaturated fatty acids (e.g. oleic acid, OA), and the n-6 and n-3, both polyunsaturated fatty acids (PUFAs). However, only the n-6 and n-3 families, derived from LA and ALA, respectively, are EFA. These must be obtained from the diet since mammals lack the desaturase enzymes necessary for the insertion of a double bond in the n-6 and n-3 positions of the fatty acid carbon chain. Fatty acid nomenclature is as follows The first number denotes the number of carbon atoms in the acyl chain and the second refers to the number of unsaturated (double) bonds. This is followed by a symbol n or co and a number that denotes the number of carbon atoms from the methyl terminal of the molecule to the first double bond. Hence, LA is 18 2(n-6), while the more unsaturated ALA is denoted as 18 3(n-3) (Figure 26.1). These fatty acids must be metabolized to their longer chain derivatives before carrying out many of their activities. 

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