Hydroperoxy fatty acids HPETE

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. 

For over 40 years it has been known that plant tissues contain lipoxygenases which catalyse the introduction of oxygen into polyunsaturated fatty acids. In 1974 Hamberg and Samuelsson found that platelets contained a 12-lipoxygenase and since that time 5- and 15-lipoxygenases have also been discovered. The immediate products are hydroperoxy fatty acids which for arachidonate substrate are hydroperoxy eicosatetraenoic acids (HPETEs). 

The finding that the endoperoxides caused platelet aggregation made it of interest to study the transformations of arachidonic acid in suspensions of human platelets. Two pathways were identified [16]. The initial reaction of one of them was catalyzed by fatty acid cyclooxygenase and led to the formation of three major end-products, i.e. 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT), malondialdehyde, and a novel hemiacetal derivative named thromboxane 82 (TXBj). The other pathway consisted of conversion of arachidonic acid into 12L-hydroperoxy-5,8,10,14-eicosatetraenoic acid (12-HPETE) by a novel lipoxygenase. The hydroperoxide was subsequently converted into a stable end-product, 12L-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) by a glutathione peroxidase [16,17]. 

The HPETEs can undergo three reactions (Figure 3.34). The hydroperoxy group can be reduced to an alcohol, thus forming an hydroxyeicosatetraenoic acid (HETE). Alternatively a second lipoxygenation elsewhere on the chain yields a dihydroxyeicosatetraenoic acid (diHETE) or a dehydration produces an epoxy fatty acid. 

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