Fatty hydroperoxidation

Autoxida.tlon. The autoxidation (7) of unsaturated fatty acids in phosphoHpids is similar to that of free acids. Primary products are diene hydroperoxides formed in a free-radical process. 

Browning Reactions. The fluorescent components formed in the browning reaction (8) of peroxidized phosphatidylethanolamine are produced mainly by interaction of the amine group of PE and saturated aldehydes produced through the decomposition of fatty acid hydroperoxides. 

Lipoxygenase-Catalyzed Oxidations. Lipoxygenase-1 catalyzes the incorporation of dioxygen into polyunsaturated fatty acids possessing a l(Z),4(Z)-pentadienyi moiety to yield ( ),(Z)-conjugated hydroperoxides. A highly active preparation of the enzyme from soybean is commercially available in purified form. From a practical standpoint it is important to mention that the substrate does not need to be in solution to undergo the oxidation. Indeed, the treatment of 28 g/L of linoleic acid [60-33-3] with 2 mg of the enzyme results in (135)-hydroperoxide of linoleic acid in 80% yield... 

Enzymatically r-BHP, NAPBQI, divicine, fatty acid hydroperoxide ,... 

Oxidation of C12-C14 n-paraffms using boron trioxide catalysts was extensively studied for the production of fatty alcohols.Typical reaction conditions are 120-130°C at atmospheric pressure. ter-Butyl hydroperoxide (0.5 %) was used to initiate the reaction. The yield of the alcohols was 76.2 wt% at 30.5% conversion. Fatty acids (8.9 wt%) were also obtained. Product alcohols were essentially secondary with the same number of carbons and the same structure per molecule as the parent paraffin hydrocarbon. This shows that no cracking has occurred under the conditions used. The oxidation reaction could be represented as ... 

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]. 

These include the mitochondrial respiratory chain, key enzymes in fatty acid and amino acid oxidation, and the citric acid cycle. Reoxidation of the reduced flavin in oxygenases and mixed-function oxidases proceeds by way of formation of the flavin radical and flavin hydroperoxide, with the intermediate generation of superoxide and perhydroxyl radicals and hydrogen peroxide. Because of this, flavin oxidases make a significant contribution to the total oxidant stress of the body. 

Vinyl monomers may be polymerized at favorable rates in an aqueous medium containing an emulsifier and a water-soluble initiator. A typical simple Tecipe would consist of the following ingredients with their proportions indicated in parts by weight 100 of monomer, 180 of water, 2 to 5 of a fatty acid soap, and 0.1 to 0.5 of potassium persulfate. Cationic soaps (e.g., dodecylamine hydrochloride) may be used instead of the fatty acid soap, and various other initiators may replace the persulfate (e.g., hydrogen peroxide and ferrous ion, or a water-soluble organic hydroperoxide). 

Corongui, F.P., Poll, G., Diansani, M.U., Cheeseman, K.H. and Slater, T.F. (1986). Lipid peroxidation and molecular damage to polyunsaturated fatty acids in rat liver. Recognition of two classes of hydroperoxides formed under conditions in vivo. Chem. Biol. Interactions 59, 147-155. 

Scheme 2.1 The key reactions that occur during lipid peroxidation, in this scheme, X represents the initiating species, which must be a highiy reactive oxidant, in order to abstract a H atom from a poiyunsaturated fatty-acid chain LH, the iipid substrate LO2, the peroxyi radicai L, the alkyl radical LOOH, the lipid hydroperoxide.

Figure 2.1 Mechanism for the oxygenation of iipids by iipoxygenase under aerobic conditions. LH, fatty acid LOOM, fatty-acid hydroperoxide Fe, the redox active centre of the enzyme.

An example of an experiment in which LDL has been treated with 15-lipoxygenase and the oxidation monitored by the formation of conjugated diene is shown in Fig. 2.2. In the absence of transition metal, a rapid increase in absorbance occurs, with no lag phase, which ceases after a period of about 90 min under these conditions. If copper is added to promote LDL oxidation at this point, LDL treated with lipoxygenase oxidizes at a faster rate with a short lag phase when compared to the control. During this procedure there is only a minimal loss of a-tocopherol and so we may ascribe the shortened lag phase to the increase in lipid peroxides brought about by lipoxygenase treatment. A similar result was found when LDL was supplemented with preformed fatty acid hydroperoxides (O Leary eta/., 1992). 

The accumulation of hydroperoxides and their subsequent decomposition to alkoxyl and peroxyl radicals can accelerate the chain reaction of polyunsaturated fatty-acid p>eroxidation leading to oxidative damage to cells and membranes as well as lipoproteins. It is well-recognized that transition metals or haem proteins, through their... 

Esterbauer et cil. (1992) have studied the in vitro effects of copper on LDL oxidation and have shown that there are three distinct stages in this process. In the first part of the reaction, the rate of oxidation is low and this period is often referred to as the lag phase the lag phase is apparently dependent on the endogenous antioxidant content of the LDL, the lipid hydroperoxide content of the LDL particle and the fatty acid composition. In the second or propagation phase of the reaction, the rate of oxidation is much faster and independent of the initial antioxidant status of the LDL molecule. Ultimately, the termination reactions predominate and suppress the peroxidation process. The extensive studies of Esterbauer et al. have demonstrated the relative importance of the endogenous antioxidants within the LDL molecule in protecting it from oxidative modification. 

Labeque, R. and Marnett, L. (1988). Reaction of haematin with allylic fatty acid hydroperoxides. Biochemistry 27, 7060-7070. 

Figure 17.2 Lipid peroxidation scheme. LH, a polyunsaturated fatty acid LOOM, lipid hydroperoxide LOH, lipid alcohol L, lipid radical LOO, lipid hydroperoxyl radical LO, lipid alkoxyl radical. Initiation the LH hydrogen is abstracted by reactive oxygen (e.g. lipid alkyl radical, lipid alkoxy radical, lipid hydroperoxyl radical, hydroxy radical, etc.) to produce a new lipid alkyl radical, L. Propagation the lipid alkyl, alkoxyl or hydroperoxyl radical abstracts hydrogen from the neighbouring LH to generate a new L radical.

Reaction yields depend on the nature of the substrate. Linseed oil contains two polyunsaturated fatty acids 50% linolenic acid and 18% linoleic acid. The corresponding hydroperoxides are obtained with low yields. 

At the end of the reaction, hydroperoxide can be easily recovered in the aqueous phase (98-99%) after its separation from the organic phase and precipitation of the enzymes. The hydroperoxides obtained are highly reactive molecules [109]. They are intermediate compounds in the lipoxygenase pathway in plants, precursors for the synthesis of hydroxy-fatty acids (i.e., ( + )-coriolic acid [38,110], and regulators of the prostaglandins biosynthesis [111-113]. 

As a reasonable biogenetie pathway for the enzymatic conversion of the polyunsaturated fatty acid 3 into the bicyclic peroxide 4, the free radical mechanism in Equation 3 was postulated 9). That such a free radical process is a viable mechanism has been indicated by model studies in which prostaglandin-like products were obtained from the autoxidation of methyl linolenate 10> and from the treatment of unsaturated lipid hydroperoxides with free radical initiators U). 

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