Polyunsaturated fatty acids synthesis

For some time, the effects of and responses to vitamin E have been interpreted in terms of an antioxidant mechanism of action. However, several observations have raised the question as to whether other mechanisms could be involved. For example, the effects of selenium and vitamin E on growth and polyunsaturated fatty acid synthesis in cultured mouse fibroblasts could not be reproduced by artificial antioxidants [198, 199]. The specific requirement of (+ )-a-toco-pherol for the phenotypic differentiation of the rotifer [200] may not be through an antioxidant mechanism. The effects of vitamin E on differentiation of neuroblastoma cells [201] and metamorphosis of various species [202] are likely to be due to a growth-factor-like action. A study on the interaction... 

Polyunsaturated fatty acid synthesis is catalyzed by acyl-lipid-desaturases, also named front-end desaturases due to their action mechanism, which proceeds via introduction of double bonds into preformed acyl chains by oxygen and electron-donor dependent desaturation, between the carboxyl group and the pre-existing unsaturation which acts as substrate. For many microsomal desaturases, the electron donors are cytochrome b5, and a small hemoprotein that operates in numerous redox reactions in plants, involving NADH-dependent acyl-group desaturation [200]. 

Wilson, R.F. H.H. Weissinger J.A. Buck G.D. Faulkner. Involvement of phospholipids in polyunsaturated fatty acid synthesis in developing soybean cotyledons. Plant Physiol. 1980, 66, 545-549. 

W26 Witting, L. A. Fatty liver induction. Effect of ethionine on polyunsaturated fatty acid synthesis. Biochim. Biophys. Acta, 296, 271-286 (1973)... 

REGULATORY FUNCTION OF A6 DESATURASE — KEY ENZYME OF POLYUNSATURATED FATTY ACID SYNTHESIS... 

INHIBITION OF POLYUNSATURATED FATTY ACID SYNTHESIS BY SALICYLIC ACID AND SALICYLHYDROXAMIC ACID AND THEIR MODES OF ACTION... 

Microsomal (0-6 desaturases use cytochrome b5 as electron donor to introduce a double bond into the co-6 position of monounsaturated oleic acid to produce polyunsaturated linoleic acid. Thus microsomal -6 desaturases play a vital role in the polyunsaturated fatty acid synthesis in angiosperms. It has been estimated that these enzymes are responsible for more than 90% of the polyunsaturated fatty acid synthesis in non-photosynthetic tissues and developing seeds of oil crops (1). 

Inhibition of Polyunsaturated Fatty Acid Synthesis by Salicyclic Acid and Salicylhydroxamic Acid and Their Modes of Action. 

Miquel, M. and Browse, J. (1992) Arabidopsis mutants deficient in polyunsaturated fatty acid synthesis. J. Biol. Chem. 267, 1502-1509. 

In mammals the introduction of new double bonds into mono- and polyunsaturated fatty acids exclusively occurs in the carboxyl end and is never directed toward the terminal methyl-group. Therefore no transition of fatty acids belonging to the linoleic acid family into those of the linolenic acid type has been observed. This has been shown by means of terminally labeled synthetic polyunsaturated fatty acids (Stoffel 1961, Klenk 1964). The complete enzyme system for polyunsaturated fatty acid synthesis is arranged on the cytoplasmic membranes. In view of the importance of polyunsaturated fatty acids for the structure of glycero-phospholipids, it is interesting to mention the acyl-transferases catalyzing the acylation of the j8-position of lysolecithin, lysophosphatidic acid and L-a-glycero-phosphate. These and other enzymes of phospholipid biosynthesis are located in the cytoplasmic reticulum, which therefore appears to be the main site of lipid synthesis of the cell. 

Wallis, J.G., Watts, J.L., and Browse, J. (2002) Polyunsaturated fatty acid synthesis what will they think of next Trends Biochem. Sci, 111, 467-473. 

Figure 3.13 Major pathways for polyunsaturated fatty acid synthesis in plants and algae.

Further discussion of the role of polyunsaturated fatty acid synthesis in the formation of prostaglandins, thromboxanes and prostacyclins will be found in section 3.4. 

Animal cells can modify arachidonic acid and other polyunsaturated fatty acids, in processes often involving cyclization and oxygenation, to produce so-called local hormones that (1) exert their effects at very low concentrations and (2) usually act near their sites of synthesis. These substances include the prostaglandins (PG) (Figure 25.27) as well as thromboxanes (Tx), leukotrienes, and other hydroxyeicosanoic acids. Thromboxanes, discovered in blood platelets (thrombocytes), are cyclic ethers (TxBg is actually a hemiacetal see Figure 25.27) with a hydroxyl group at C-15. 

Polysaccharide. 974, 1000-1001 synthesis of, 1001-1002 Polystyrene, uses of, 242 Polytetrafluoroethylene, uses of, 242 Polyunsaturated fatty acid, 1061... 

A molecular variation of plasma membrane has been reported by Puccia et al. Reduction of total lipids (XL) content and significant variations of triglyceride (TG) and phospholipids (PL) fractions were observed as a consequence of exposure of C. intestinalis ovaries to TBTCl solutions. In particular, an evident TG decrease and a PL increase were observed, which probably provoked an increment in membrane fluidity, because of the high concentration of long chain fatty acids and, as a consequence, PL. This could be a cell-adaptive standing mechanism toward the pollutants, as observed in Saccharomyces cerevisiae. Also the increase in the content of the polyunsaturated fatty acids (PUPA), important in the synthesis of compounds such as prostaglandin which are present in the ovary in a stress situation, was probably a consequence of a defense mechanism to the stress provoked by the presence of TBTCl. 

SYNTHESIS OF POLYUNSATURATED FATTY ACIDS INVOLVES DESATURASE ELONGASE ENZYME SYSTEMS... 

Elucidation of the physiological role of arachidonic acid 13 and other polyunsaturated fatty acids, particularly the role of all Z-4,7,10,13,16,19-decosahexaenoic acid 14, found in brain, required the corresponding stable-isotope labelled material1011. The deuteriated phosphonium salt 15, the key intermediate used in the synthesis of title compound 16 (equation 8), has been prepared in 19% overall yield12 starting with ethanol-D6 (equation 7). 

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. 

Arachidonic acid (C20 4 n-6) is the precursor for the synthesis of prostaglandin molecules (Section 4.4.4), which have a wide range of biochemical effects on for example, the perception of pain, inflammation, blood clotting and smooth muscle contraction. Docosahexaenoic acid (DHA, C22 6) and eicosapentaenoic acid (EPA, C20 5) are both n-3 long-chain polyunsaturated fatty acids (PUFA) which have been shown to have significantly beneficial effects on intellectual development and inflammatory conditions such as asthma and cardiovascular disease. 

Polyunsaturated fatty acids Polyunsaturated fatty acids are provided in the triacylglycer-ols on phospholipids in the feeds. They are required for synthesis of phospholipids, which are required for formation of new membranes in proliferating cells, and as precursors for fat signalling molecules that are important in control of proliferation (see below). 

Cholesterol The pathway for synthesis of cholesterol is described in Appendix 11.9. Cholesterol is important in the structure of membranes since it can occupy the space that is available between the polyunsaturated fatty acids in the phospholipid (Chapter 4). In this position, cholesterol restricts movement of the fatty acids that are components of the phosphoglycerides and hence reduces membrane fluidity. Cholesterol can be synthesised de novo in proliferating cells but it can also be derived from uptake of LDL by the cells, which will depend on the presence of receptors for the relevant apoUpoproteins on the membranes of these cells (Appendix 11.3). 

In 1990, Triantaphylidds and coworkers reported on the preparative enzymatic synthesis of hnoleic acid (135) hydroperoxide 24a using soybean lipoxygenase-1. In this dioxygenation asymmetry is induced by the catalyst, the enzyme. The reaction was later used by Dussault and also by Baba and coworkers as key step in the preparation of more complex peroxides. The enzyme is a non-heme iron dioxygenase which catalyzes the incorporation of dioxygen into polyunsaturated fatty acids to yield E,Z conjugated diene hydroperoxides 24a-d. With this enzymatic method, the hydroperoxide 24a could... 

Facciotti, D. Metz, J.G. Lassner, M. (1998) Polyketide synthesis graes of marine microbe and production of polyunsaturated fatty acids and PUFA-containing plant oils with transgenic plants. PCT Int. Appl. 10 Dec. to Calgene LLC Co) Chem. Abstr., 1999,130, 62050. 

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