Unsaturated fatty acids, formation

Marrakchi, H., Choi, K.H. and Rock, C.O. A new mechanism for anaerobic unsaturated fatty acid formation in Streptococcus pneumoniae. J Biol Chem, 211 (2002) 44809-A4816. 

Figure 3.12 Important pathways for unsaturated fatty acid formation in animals.

The state of knowledge in the early 1990s of the effects of fat on health lacks clarity and general agreement. There is great support for the thesis that fully saturated fats are associated with problems of atherosclerosis and arterial fatty deposit, but there is evidence that stearates, which are saturates, are only poorly utilized in human digestion. Another body of work has estabUshed a connection between unsaturated fatty acids and a better state of arterial health and lowered fat body attachment to the arterial wall (23) contrary evidence exists that highly unsaturated fats polymerize more readily and thus contribute to arterial plaque formation. 

Structure and Mechanism of Formation. Thermal dimerization of unsaturated fatty acids has been explaiaed both by a Diels-Alder mechanism and by a free-radical route involving hydrogen transfer. The Diels-Alder reaction appears to apply to starting materials high ia linoleic acid content satisfactorily, but oleic acid oligomerization seems better rationalized by a free-radical reaction (8—10). 

Mammals can add additional double bonds to unsaturated fatty acids in their diets. Their ability to make arachidonic acid from linoleic acid is one example (Figure 25.15). This fatty acid is the precursor for prostaglandins and other biologically active derivatives such as leukotrienes. Synthesis involves formation of a linoleoyl ester of CoA from dietary linoleic acid, followed by introduction of a double bond at the 6-position. The triply unsaturated product is then elongated (by malonyl-CoA with a decarboxylation step) to yield a 20-carbon fatty acid with double bonds at the 8-, 11-, and 14-positions. A second desaturation reaction at the 5-position followed by an acyl-CoA synthetase reaction (Chapter 24) liberates the product, a 20-carbon fatty acid with double bonds at the 5-, 8-, IT, and ITpositions. 

Applications of peroxide formation are underrepresented in chiral synthetic chemistry, most likely owing to the limited stability of such intermediates. Lipoxygenases, as prototype biocatalysts for such reactions, display rather limited substrate specificity. However, interesting functionalizations at allylic positions of unsaturated fatty acids can be realized in high regio- and stereoselectivity, when the enzymatic oxidation is coupled to a chemical or enzymatic reduction process. While early work focused on derivatives of arachidonic acid chemical modifications to the carboxylate moiety are possible, provided that a sufficiently hydrophilic functionality remained. By means of this strategy, chiral diendiols are accessible after hydroperoxide reduction (Scheme 9.12) [103,104]. 

Cowan Teeter (1944) reported a new class of resinous substances based on the zinc salts of dimerized unsaturated fatty acids such as linoleic and oleic acid. The latter is referred to as dimer acid. Later, Pellico (1974) described a dental composition based on the reaction between zinc oxide and either dimer or trimer acid. In an attempt to formulate calcium hydroxide cements which would be hydrolytically stable, Wilson et al. (1981) examined cement formation between calciimi hydroxide and dimer acid. They found it necessary to incorporate an accelerator, alimiiniiun acetate hydrate, Al2(OH)2(CHgCOO)4.3H2O, into the cement powder. 

It should be noted that Reaction (4) is not a one-stage process.) Both free radical N02 and highly reactive peroxynitrite are the initiators of lipid peroxidation although the elementary stages of initiation by these compounds are not fully understood. (Crow et al. [45] suggested that trans-ONOO is protonated into trans peroxynitrous acid, which is isomerized into the unstable cis form. The latter is easily decomposed to form hydroxyl radical.) Another possible mechanism of prooxidant activity of nitric oxide is the modification of unsaturated fatty acids and lipids through the formation of active nitrated lipid derivatives. 

The unique characteristic of free peroxyl radicals formed from unsaturated fatty acids is their ability to transform into cyclic radicals. This reaction is of utmost importance because it leads to highly biologically active compounds. Enzymatic oxidation of arachidonic acid catalyzed by COX results in the formation of prostaglandins having various physiopathological... 

In the last decade numerous studies were dedicated to the study of biological role of nonenzymatic free radical oxidation of unsaturated fatty acids into isoprostanes. This task is exclusively difficult due to a huge number of these compounds (maybe many hundreds). Therefore, unfortunately, the study of several isoprostanes is not enough to make final conclusions even about their major functions. F2-isoprostanes were formed in plasma and LDL after the treatment with peroxyl radicals [98], It is interesting that their formation was observed only after endogenous ascorbate and ubiquinone-10 were exhausted, despite the presence of other antioxidants such as urate or a-tocopherol. LDL oxidation was followed by... 

As mentioned earlier, oxidation of LDL is initiated by free radical attack at the diallylic positions of unsaturated fatty acids. For example, copper- or endothelial cell-initiated LDL oxidation resulted in a large formation of monohydroxy derivatives of linoleic and arachi-donic acids at the early stage of the reaction [175], During the reaction, the amount of these products is diminished, and monohydroxy derivatives of oleic acid appeared. Thus, monohydroxy derivatives of unsaturated acids are the major products of the oxidation of human LDL. Breuer et al. [176] measured cholesterol oxidation products (oxysterols) formed during copper- or soybean lipoxygenase-initiated LDL oxidation. They identified chlolcst-5-cnc-3(3, 4a-diol, cholest-5-ene-3(3, 4(3-diol, and cholestane-3 3, 5a, 6a-triol, which are present in human atherosclerotic plaques. 

Vitamin Ba (pyridoxine, pyridoxal, pyridoxamine) like nicotinic acid is a pyridine derivative. Its phosphorylated form is the coenzyme in enzymes that decarboxylate amino acids, e.g., tyrosine, arginine, glycine, glutamic acid, and dihydroxyphenylalanine. Vitamin B participates as coenzyme in various transaminations. It also functions in the conversion of tryptophan to nicotinic acid and amide. It is generally concerned with protein metabolism, e.g., the vitamin B8 requirement is increased in rats during increased protein intake. Vitamin B6 is also involved in the formation of unsaturated fatty acids. 

Also Enterobacteria are able to synthesize unsaturated fatty acids and to incorporate these into the lipid A component. Thus, when grown at low temperature (10- 15°C) E. coli (143), Salmonella spp. (142), P. mirabilis (37), and Y. enterocolitica (145) are incorporated into the lipid A component unsaturated fatty acids that are not present in LPS of bacteria grown at 370 C. For E. coli and Salmonella strains grown at low temperatures, it was found that (Z)-A9-hexadecenoic acid (A9-16 1) was incorporated at the expense of 12 0 (142,143), however, not quantitatively. Further investigations of these lipid A by l.d.-m.s. revealed that the unsaturated fatty acid specifically replaced the 12 0 residue in 14 0[3-6>( 12 0)] that is bound to GlcN(II) (37). A similar effect of thermoadaptation, resulting in the formation of amide-bound 14 0[3-6>(A9-16 1)], was detected in P. mirabilis and Y. enterocolitica (145). 

The last essential dietary components to which we will refer and which were also discovered through feeding experiments with rats, are certain unsaturated fatty acids identified as linoleic, linolenic, and arachidonic acids by Burr and Burr in 1930. The acids are required for the formation of complex lipids which are essential in membranes for the maintenance of their fluidity (Chapter 9). Deficiencies lead to a dermatitis which does not respond to additional B vitamin supplements or to oleic acid. 

Additionally, it should be observed that the thermal oxidability and oxidative polymerization of the unsaturated fatty acids follows the trend linolenic > linoleic > oleic > > palmitoleic (Martinenghi, 1963). The oxidation involves, as first step, the abstraction of a hydrogen atom in allylic position to the double bonds. Certainly, this process is favoured in the case of fatty acids with two or more unconjugated double bonds where the formation of a free radical by allylic hydrogen abstraction leads quite necessarily to double bonds slippage with formation of conjugated double bonds ... 

The C60 and C70 reactivity with the vegetable oils at first glance could appear as an obstacle in the use of fullerene solutions in vegetable oils. Apart from the fact that one could use fully saturated fatty acids derivatives as vehicle for fullerenes delivery, which are not reactive with them, the formation of adducts between the unsaturated fatty acids and fullerenes could be exploited not only in the stabilization of the systems fullerenes-vegetable oils, but also in the alteration and, may be in the attenuation of the fullerene reactivity in in vivo and in a very gradual release of the fullerenes-fatty acids derivatives in living systems. 

Studies of the reaction of ozone with simplified lipid systems have shown that malonaldehyde can be produced by direct ozonolysis. The use of malonaldehyde assay as an index of lipid peroxidation is therefore invalid in ozone studies. Liposomes formed from egg lecithin and prepared in aqueous media were quite resistant to ozone, but the contribution of polyconcentric spheres to this resistance has not been fully assessed. However, the bilayer configuration, with the susceptible unsaturated fatty acids shielded from ozone by the hydrophilic areas of the molecule, may be resistant. In hexane, where the fatty acid moieties are exposed, ozone reacts stoichiometrically with the double bonds. The experiments with aqueous suspensions of phosphatidylcholine gave no evidence of the formation of lipid peroxides,nor did experiments with films of fatty acids exposed to ozone. ... 

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