Linoleate desaturase

In sharp contrast to these experiments, Hawke et al. (1980) have clearly shown that both etiolated and greened maize leaf tissue rapidly convert oleic acid to linoleic acid and thence linolenate. Thus, the kinetics of the appearance and disappearance of oleate desaturase and linoleate desaturase differ markedly in different tissues, namely, cucumber cotyledonous tissue and maize leaf tissue. It becomes of obvious importance therefore that, in future research, the type of tissue, the history of the tissue, and the regime of conditions impinging on these tissues be taken into consideration before broad generalities can be stated. 

Kabbaj, A., Abbott, A. and Berville, A. 1996. Expression of stearate, oleate and linoleate desaturase genes in sunflower with normal and high-oleic contents. In Proceedings of the 14 International Sunflower Conference, Beijing, 12-20 June 1996. pp. 60-65. 

DCMU inhibitory effect on linoleate desaturation appeared in 24 hours after the beginning of pea shoot incubation with l- C oleate the percentage of C-linolenate decreased twice in the presence of DCMU (Tabl. 1). On the one hand, the li-nolenate percentage decrease may be caused by the decrease of the reduced pyridine nucleotide level in the cells in the presence of DCMU. Besides, the possibility of electron transfer to linoleate desaturase both from NADPH and from H2O may be... 

Figure 23-4. Conversion of linoleate to arachido-nate. Cats cannot carry out this conversion owing to absence of A desaturase and must obtain arachidonate in their diet.

Some pheromone components are dienes and these can be produced by either the action of two desaturases or one desaturase and isomerization around the double bond. Some dienes with a 6,9-double bond configuration are produced using linoleic acid. Desaturases that utilize monounsaturated acyl-CoA substrates include A5 [39], A9 [36,40], All [41],A12 [42],andA13 [43].These can act sequentially to produce the diene [41,42] or conjugated dienes could be produced by the action of one desaturase followed by isomerization [44-47]. 

FIGURE 3-7 Pathways for the interconversion of brain fatty acids. Palmitic acid (16 0) is the main end product of brain fatty acid synthesis. It may then be elongated, desaturated, and/or P-oxidized to form different long chain fatty acids. The monoenes (18 1 A7, 18 1 A9, 24 1 A15) are the main unsaturated fatty acids formed de novo by A9 desaturation and chain elongation. As shown, the very long chain fatty acids are a-oxidized to form a-hydroxy and odd numbered fatty acids. The polyunsaturated fatty acids are formed mainly from exogenous dietary fatty acids, such as linoleic (18 2, n-6) and a-linoleic (18 2, n-3) acids by chain elongation and desaturation at A5 and A6, as shown. A A4 desaturase has also been proposed, but its existence has been questioned. Instead, it has been shown that unsaturation at the A4 position is effected by retroconversion i.e. A6 unsaturation in the endoplasmic reticulum, followed by one cycle of P-oxidation (-C2) in peroxisomes [11], This is illustrated in the biosynthesis of DHA (22 6, n-3) above. In severe essential fatty acid deficiency, the abnormal polyenes, such as 20 3, n-9 are also synthesized de novo to substitute for the normal polyunsaturated acids. 

The question arises whether inhibition of the desaturase for this particular pathway can be overcome. The answer is yes. The product of the A desaturase when desaturating linoleic acid is y-linolenic acid. Supplementation of the diet with y-linolenic acid, which bypasses the A desaturase reaction, has been used to increase the formation of dihomo-y-linolenic acid and arachidonic acid (Figure... 

Enzyme complexes occur in the endoplasmic reticulum of animal cells that desaturate at A5 if there is a double bond at the A8 position, or at A6 if there is a double bond at the A9 position. These enzymes are different from each other and from the A9-desaturase discussed in the previous section, but the A5 and A6 desaturases do appear to utilize the same cytochrome b5 reductase and cytochrome b5 mentioned previously. Also present in the endoplasmic reticulum are enzymes that elongate saturated and unsaturated fatty acids by two carbons. As in the biosynthesis of palmitic acid, the fatty acid elongation system uses malonyl-CoA as a donor of the two-carbon unit. A combination of the desaturation and elongation enzymes allows for the biosynthesis of arachidonic acid and docosahexaenoic acid in the mammalian liver. As an example, the pathway by which linoleic acid is converted to arachidonic acid is shown in figure 18.17. Interestingly, cats are unable to synthesize arachidonic acid from linoleic acid. This may be why cats are carnivores and depend on other animals to make arachidonic acid for them. Also note that the elongation system in the endoplasmic reticulum is important for the conversion of palmitoyl-CoA to stearoyl-CoA. 

Synthesis in mammalian tissues of arachidonic acid from linoleic acid. The A5 and A6 desaturases are separate enzymes and are also different from the A9 desaturase (fig. 18.16). The mechanisms, however, seem to be the same, involving cytochrome b5 and cytochrome reductase. The enzymes for elongation of unsaturated fatty acid such as 18 3 to 20 3 occur on the endoplasmic reticulum. 

Guiet et al. (2003) demonstrated that deuterium (2H) distribution in fatty acids was non-statistical and could be related to isotopic discrimination during chain extension and desaturation. Petroselinic acid (C18 1A6) (Fig. 21.4), a fatty acid characteristic of the seeds of the Apiaceae, has been shown to be biosynthesized from palmitoyl-ACP (C16 0) by two steps, catalysed by a dedicated A4-desaturase and an elongase. The isotopic profile resulting from this pathway is similar to the classical plant fatty acid pathway, but the isotopic fingerprint from both the desaturase and elongase steps shows important differences relative to oleic and linoleic acid biosynthesis. 

Choi, Y., Kim, Y-C., Han, Y-B., Park, Y., Pariza, M.W., Ntambi, J.M. 2000. The trans-10, dr-12 isomer of conjugated linoleic acid downregulates stearoyl-CoA desaturase 1 gene expression in 3T3-L1 adipocytes. J. Nutr. 130, 1920-1924. 

The term conjugated linoleic add (CLA) refers to a mixture of positional and geometric isomers of linoleic add with a conjugated double bond system milk fat can contain over 20 different isomers of CLA. CLA isomers are produced as transient intermediates in the rumen biohydrogenation of unsaturated fatty acids consumed in the diet. However, cis-9, trans-11 CLA, known as rumenic acid (RA), is the predominant isomer (up to 90% of total) because it is produced mainly by endogenous synthesis from vaccenic acid (VA). VA is typically the major biohydrogenation intermediate produced in the rumen and it is converted to RA by A9-desaturase in the mammary gland and other tissues. 

Figure 3.2. Pathways for ruminal and endogenous synthesis of rumenic acid (cis-9, trans-11 CLA) in the lactating dairy cow. Pathways for biohydrogenation of linoleic and linolenic acids yielding vaccenic acid trans-11 18 1) are shown in the rumen box and endogenous synthesis by A9-desaturase is shown in the mammary gland box. Adapted from Bauman et at. (2003).

Griinari, J.M., Corl, B.A., Lacy, S.H., Chouinard, P.Y., Nurmela, K.V.V., Bauman, D.E. 2000b. Conjugated linoleic acid is synthesized endogenously in lactating dairy cows by A9 — desaturase. J. Nutr. 130, 2285-2291. 

Lock, A.L., Garnsworthy, P.C. 2003. Seasonal variation in milk conjugated linoleic acid and A9-desaturase activity in dairy cows. Livest. Prod. Sci. 79, 47-59. 

Park, Y., Storkson, J.M., Ntambi, J.M., Cook, M.E., Sih, C.J., Pariza, M.W. 2000. Inhibition of hepatic stearoyl-CoA desaturase activity by trans-10, cis-12 conjugated linoleic acid and its derivatives. Biochim. Biophys. Acta 1486, 285-292. 

Perfield, J.W., Delmonte, P., Lock, A.L., Yurawecz, M.P., Bauman, D.E. 2004a. trans-10, trans-12 conjugated linoleic acid (CLA) reduces the A9-desaturase index without affecting milk fat yield in lactating dairy cow. J. Dairy Sci. 87 (Suppl. 1), 128. 

The n-6 and n-3 families are two principal families of polyunsaturated fatty acids occurring in nature and derived biosynthetically from linoleic (9-cis, 12-cw-octadecadienoic or C18 2n-6) and a-linoleific (9-cis, 12-ds, 15-c/5-octadecatrienoic or C18 3n-3) acids, respectively (Fig. 6). Both fatty acids are synthesized in plants that can insert double bonds at the A9, A12, and A15 positions in a C18 chain but not in aifimals (they can insert double bonds at the A9, but not at A12 and A15). Therefore, these two acids are essential dietary components. In aifimals, additional double bonds are inserted between the carboxyl group and the A9 position by A 5 and A 6 desaturase enzymes, and the chain can also be extended in two carbon units at the carboxyl end of the molecules by elongase enzymes. 

The reaction catalyzed by delta-6-desaturase enzyme is the slowest reaction in the metabolic pathway of LA and is considered as a rate-limiting step (4, 5). Activity of this enzyme further decreases with age and in people suffering from various diseases, including arthritis, diabetes, hypertension, eczema, psoriasis, and so on. Lifestyle factors like stress, smoking, excessive consumption of alcohol, linoleic acid (6), saturated and trans-fatty acids and nutritional deficiencies of Vitamin B6, zinc (7), and magnesium inhibit this desaturase. As a result of limitations in in vivo production of GLA, supplementation with preformed GLA is becoming important. This has led to interest in development and commercialization of the sources of GLA. 

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