15-HPETE 155-hydroperoxy

HPCA ([4-(3-heptyl)pyridine-2-carboxylic add]), transihon metal peroxides, 1116 15-HPETE (155 -hydroperoxy-5,811z,... 

LT leukotriene, TX thromboxane, HPETE hydroperoxy eicosatetraenoic acid, hydroxy eicosatetraenoic acid, HHT12 hydroxyheptadecatrienoic acid (17 carbon), MDA malondialdehyde (3 carbon)... 

Lipoxygenation is the major pathway of dioxygenation of arachidonic acid in blood platelets and leads to the 12-5-hydroperoxy acid 12-HPETE and the corresponding 12-hydroxy acid 12-HETE. Several pathways for the synthesis of 12-HETE have been developed. However, despite the availability of this substance, its biological role remains undetermined. 

HPETE, 12(.S)-hydroperoxyeicosatetraenoic acid 15-HPETE, 15(S)-hydropcroxycicosatctracnoic acid 4-HPNE, 4-hydroperoxy-2-nonenal... 

Inhibition and stimulation of LOX activity occurs as a rule by a free radical mechanism. Riendeau et al. [8] showed that hydroperoxide activation of 5-LOX is product-specific and can be stimulated by 5-HPETE and hydrogen peroxide. NADPH, FAD, Fe2+ ions, and Fe3+(EDTA) complex markedly increased the formation of oxidized products while NADH and 5-HETE were inhibitory. Jones et al. [9] also demonstrated that another hydroperoxide 13(5)-hydroperoxy-9,ll( , Z)-octadecadienoic acid (13-HPOD) (formed by the oxidation of linoleic acid by soybean LOX) activated the inactive ferrous form of the enzyme. These authors suggested that 13-HPOD attached to LOX and affected its activation through the formation of a protein radical. Werz et al. [10] showed that reactive oxygen species produced by xanthine oxidase, granulocytes, or mitochondria activated 5-LOX in the Epstein Barr virus-transformed B-lymphocytes. 

Figure 6.17. Leukotriene formation in neutrophils. Arachidonic acid, which is released from membrane phospholipids by the action of either phospholipase A2 or diacylglycerol lipase (see Fig. 6.13), is oxygenated by 5-lipoxygenase to yield 5 hydroperoxy-6,8,11,14 eicosa-tetraenoic acid (5-HPETE). This is then converted into 5 hydroxy-6,8,11,14 eicosatetra-enoic acid (5-HETE) and leukotriene (LT) A4. LTA4 may then be enzymically converted into LTC4 and LTB4. LTB4 is the major product in activated neutrophils.

The hydroperoxides obtained on thermal oxidation of cholesteryl acetate (191e) can be selectively separated by SPE and elution with a polar solvent. After reduction to the corresponding alcohols by NaBH4 and further derivatization to the trimethylsilyl ether, the products can be subjected to GLC with ion-trap MS detection. It can be thus demonstrated with the aid of standards that under the oxidation conditions (160 °C for 90 min) only the 7-position is attacked, leading to the la- and 7/3-hydroperoxy derivatives, while the plausible 4-position remains unscathed . Treatment of erythrocite ghosts with t-BuOOH causes a manyfold content increase of 5-hydroxyeicosatetraenoic acid (5-HETE), 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and 5-oxoeicosatetraenoic acid (5-oxo-ETE) residues of phospholipids. These acids can be separated by HPLC, identified and quantitized by tandem MS . ... 

The lipoxygenase system also competes for released arachidonic acid in a way that seems to be tissue-selective, giving rise to hydroperoxy fatty acids (HPETE) which can be converted into leukotrienes or reduced to hydroxy fatty acid (HETE) products [115]. The basic scheme for these metabolic conversions involving arachidonic acid is presented in Figure 5.2. Both of the main enzymatic pathways of arachidonic acid metabolism are thought to involve free-radical-mediated reactions [108] and the antioxidant capacity of vitamin E could therefore allow the vitamin to modify the products of these pathways. 

The other metabolic pathway derived from arachidonic acid is through the activity of the lypoxygenase-12 (2-LOX) (Fig. 5). 2-LOX converts arachidonic acid (AA) to 12-hydroperoxy-5,8,10,14-eicosatetraenoic acid (12-HPETE) that is rapidly reduced by peroxidases to the stable 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE). In... 

Lipoxygenase 5 converts arachidonic acid into 5-hydroperoxy-eicosatetraenoic acid (5-HPETE), which is the precursor of leukotrienes. Leukotrienes... 

The acronym HPETE describes a hydroperoxy-eicosatetraenoic acid and a HETE is a monohydroxy-eicosanoid. Some examples are illustrated in Scheme 1.1. 

As detailed in Scheme 1.4 the primary biosynthetic step in this cascade is the introduction of a hydroperoxy group at the 5-position by a 5-lipoxygenase enzyme to give the hydroperoxy-eicosanoid 5-HPETE. 

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,...

GGTP-gamnu-gluUmyl transpeptidase 5-HPETE - 5 -hydroperoxy-6,8,11,14-eicosatetraenoic acid 5-HPETE- 5-hydroxy 6,8,11,14 eicosatetraenoic acid... 

LTs are produced by the action of 5-lipoxygenase (5-LO) which inserts a diatomic oxygen at carbon atom-5 of AA yielding 5(5)-hydroperoxy eicosatetraenoic acid (5-HpETE). 

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