13-13-HPODE

Rgure 2.3 The antioxidant activity of butyiated hydroxytoluene in the presence of exogenous iipid hydroperoxides. The oxidation of LDL was monitored by measuring the increase in absorbance at 234 nm as described in Fig. 2.2 and the lag phase (time before the phase of maximum rate of oxidation) estimated as described by Esterbauer et at. (1989). Samples of LDL were supplemented with the cortcentrations of 13-hydroperoxyoctadecanoic acid (13-HPODE) indicated and in the presence of 3 fM BHT. The lag phase in the absence of BHT for this preparation of LDL was 48 min. 

FIGURE 25.4 Mechanism of conversion of 13-hydroperoxy-9,ll-octadecadienoic acid (13-HPODE) into 4-hydroxynonenal (4-HNE). (Adapted from C Schneider, KA Tallman, NA Porter, AR Brash. J Biol Chem 276 20831-20838, 2001. With permission.)... 

The process is induced by minimal amounts of 13-HPODE [154], which transform the Fe " ion in the active center of lipoxygenase to Fe ion. Thus the enzyme becomes able to react with a double allylically activated methylene group of a LH molecule (representing in this case a PUFA) by abstraction of a hydrogen atom. The hydrogen atom is transformed to a proton by release of an electron from the Fe ion in the... 

Scheme 2 Generation of 9- and 13-HPODEs and 9- and 13-HODE by lipidperoxidation of linoleic acid.

Lipoxygenase derived from soybean transforms linoleic acid at pH 9.2 nearly exclusively into 13S-hydroperoxy-9Z-l lE-octadecadienoic acid (13S-HPODE, Scheme 4) and linoleinic acid into 16S-9Z 12Z,14E-octadecadienoic acid (13S-HPOTE, Scheme 5) [155]. 

A mixture of 9S-HPODE and 13S-HPODE is obtained when soybean lipoxygenase reacts with linoleic acid at pH 6,4 [156]. Lipoxygenase of tomatoes [157] produces mainly 9S-10E,12Z-octadecadienoic acid (9S-HPODE, Scheme 4) from linoleic acid and 9S,10E,12Z,15Z-octadecatrienoic acid (9S-HPOTE, Scheme 5) from linolenic acid. 

Another important LPO product of linoleic acid is hexanal. It is generated from 13-HPODE as well as from 9-HPODE a similar rearrangement reaction as outlined in Scheme 9 starting with 9-HPODE generates hexanal and 12-oxo-9-dodecenoic acid, which suffer rearrangement of the double bond to traumatic acid (Scheme 11) [205]. 

Scheme 11 Generation of hexanal and traumatic acid from 13-HPODE...

Figure 5.2 Non-enzymatic degradation of 9- and 13-HPODE and 5- and 15-HPETE. (a) Transition metals and vitamin C mediate the decomposition of lipid hydroperoxides and produce several reactive, bifunctional electrophiles 4-hydroperoxy-2-nonenal,...

HETE. The 15-lipoxygenase (15-LOX) has been the most extensively characterized pathway in the reticulocytes, leukocytes, and airway epidermal cells (24-27). An outline in Figure 5 shows that 15-LOX can, on the one hand, catalyze the abstraction of a proton from C-13 of 20-carbon AA to produce 155-hydroperoxyeicosatetraenoic acid (155-HPETE), whereas on the other hand, the 18-carbon linoleic acid is converted mainly to 13-hydroperoxyoctadecadienoic acid (13-HPODE) and 9-hydroperoxy-10,12- , Z-octadecadienoic acid (9-HPODE) in the ratio of 10 1 (28). Both the 155-HPETE (intermediate) from AA and 13-HPODE (intermediate) from linoleic acid can be further metabolized by glutathione peroxidase to mainly monohydroxylated 15S-HETE and 13-hydroxy-octadecadienoic acid (HODE), respectively. 

Fig. 1. Oxidative metabolism of linoleic acid by the human epidermis. Abbreviations 13-HPODE, 13-hydroperoxide octadecadienoic acid 13-HODE, 13-hydroxyoctadecadienoic acid.

Primary products from linolac acid autoxidation the conjugated 9- and 13-HPODE and the 6/s-allylic 11-HPODE... 

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