Fatty acids hydroperoxides

Pure fatty acid hydroperoxides are very toxic to experimental animals when administered intravenously (i.v.) but not oraUy (Horgan et al., 1957 Olcott and Dolev, 1963 Findlay et al., 1970). Cortesi and Privett (1972) have shown that the 24-h lethal i.v. dose of a high purity preparation of methyl linoleate hydroperoxides in adult male rats was approximately 0.07 mmol/100 g body weight, and that the major effect of injected linoleate hydroperoxides was on the lungs. Also, vitamin E deficiency symptoms such as encephalomalacia in chicks (Nishida et al., 1960), and creatinuria and erythrocyte hemolysis in rabbits (Kokatnur et al., 1966) have been observed in animals infused with methyl linoleate hydroperoxides. 

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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. 

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

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

Nature of Oxidants Generated From Fatty Acid Hydroperoxides... 

Support for this conclusion is provided by the hydroperoxide specificity of BP oxidation. The scheme presented in Figure 6 requires that the same oxidizing agent is generated by reaction of h2°2/ peroxy acids, or alkyl hydroperoxides with the peroxidase. Oxidation of any compound by the iron-oxo intermediates should be supported by any hydroperoxide that is reduced by the peroxidase. This is clearly not the case for oxidation of BP by ram seminal vesicle microsomes as the data in Figure 7 illustrate. Quinone formation is supported by fatty acid hydroperoxides but very poorly or not at all by simple alkyl hydroperoxides or H2C>2. The fact that... 

Figure 8. Proposed mechanism of the generation of peroxyl radicals by reaction of hematin with unsaturated fatty acid hydroperoxides. ...

Significance of Fatty Acid Hydroperoxide-Dependent PAH Oxidation... 

Figure 9. Stereochemical differences between fatty acid hydroperoxide- and mixed-function oxidase-dependent oxidation of ( ) -BP-7,8-dihydrodiol.

As mentioned earlier, when NO concentration exceeds that of superoxide, nitric oxide mostly exhibits an inhibitory effect on lipid peroxidation, reacting with lipid peroxyl radicals. These reactions are now well studied [42-44]. The simplest suggestion could be the participation of NO in termination reaction with peroxyl radicals. However, it was found that NO reacts with at least two radicals during inhibition of lipid peroxidation [50]. On these grounds it was proposed that LOONO, a product of the NO recombination with peroxyl radical LOO is rapidly decomposed to LO and N02 and the second NO reacts with LO to form nitroso ester of fatty acid (Reaction (7), Figure 25.1). Alkoxyl radical LO may be transformed into a nitro epoxy compound after rearrangement (Reaction (8)). In addition, LOONO may be hydrolyzed to form fatty acid hydroperoxide (Reaction (6)). Various nitrated lipids can also be formed in the reactions of peroxynitrite and other NO metabolites. 

LOX-catalyzed oxidation of LDL has been studied in subsequent studies [26,27]. Belkner et al. [27] showed that LOX-catalyzed LDL oxidation was not restricted to the oxidation of lipids but also resulted in the cooxidative modification of apoproteins. It is known that LOX-catalyzed LDL oxidation is regio- and enantio-specific as opposed to free radical-mediated lipid peroxidation. In accord with this proposal Yamashita et al. [28] showed that LDL oxidation by 15-LOX from rabbit reticulocytes formed hydroperoxides of phosphatidylcholine and cholesteryl esters regio-, stereo-, and enantio-specifically. Sigari et al. [29] demonstrated that fibroblasts with overexpressed 15-LOX produced bioactive minimally modified LDL, which is probably responsible for LDL atherogenic effect in vivo. Ezaki et al. [30] found that the incubation of LDL with 15-LOX-overexpressed fibroblasts resulted in a sharp increase in the cholesteryl ester hydroperoxide level and a lesser increase in free fatty acid hydroperoxides. 

MATSUI, K., SHIBUTANI, M., HASE, T., KAJIWARA, T., Bell pepper fruit fatty acid hydroperoxide lyase is a cytochrome P450 (CYP75B) in many plant tissues, FEBS Lett., 1996, 394,21-24. 

SONG, W.C., FUNK, C.D., BRASH, A.R., Molecular cloning of an allene oxide synthase A cytochrome P450 specialized for the metabolism of fatty acid hydroperoxides, Proc. Natl. Acad. Sci. USA, 1993, 90, 8519-8523. 

MATSUI, K., WILKINSON, J., HIATT, B., KNAUF, V., KAJIWARA, T., Molecular cloning and expression of Arabidopsis fatty acid hydroperoxide lyase, Plant Cell Physiol., 1999,40,477-481. 

FIGURE 6 Speculative mechanism of Crl hydrocarbon biosynthesis from fatty acid hydroperoxides in algae. Homolytic cleavage of the hydroperoxide is assumed to give an allyl radical, which cyclizes to the thermolabile (1S,2R)-cyclopropane. The sequence is terminated by transfer of a hydrogen radical from C(16) to the -X-0 function. The cyclopropane rearranges to (6S)-ectocarpene as shown in Figure 4. 

Fatty acid hydroperoxides can be separated from each other and other lipids by MEKC followed by FLD according to equation 34 with 106a, using as catalyst microperoxidase-11 immobilized on the wall of a small capillary coupled at the end of the electrophoresis track. MEKC with DA-UVD can be applied for separation of unsaturated fatty acids from the mixture of hydroperoxides obtained on oxidation with 102 . ... 

The negative ion electrospray MS of fatty acid hydroperoxides exhibits various typical features that may be useful for characterization of this type of compounds, such as loss of small neutral molecules and fragmentation associated with the position of the OOH group. The [M — H] and [M — H2O peaks are usually most abundant and cleavage of the double bond allylic to the hydroperoxy group is also observed. The features of the fragmentation after loss of H2O in the MS of a fatty acid hydroperoxide are the same as those observed in the MS of the analogous keto acid . ... 

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