5-Hydroperoxy-6,8,11,14-eicosatetraenoic acid 5-HPETE

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). 

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. 

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). 

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

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... 

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

Leukotrlenes and other Mediators - Comprehensive reviews on the chemistry, biosynthesis and metabolism, - and pharmacologyi of LTs have appeared (see also Chapter 24). Chiral starting materials have been employed in the enantiospecific synthesis of LTs C, and LTF, and LTF sulfone have been synthesized and their biological activities determined in the guinea pig (GP). Total syntheses of LTB, (non-carbohydrate based), LTB and 14,15-LTA, have been reportedIn the biosynthesis of LTs in human PMNs, it was shown that the 7-H (pro-S) hydrogen is removed from arachldonic acid (AA) to form 5-hydroperoxy-6E, 8Z, IIZ, 14Z-eicosatetraenoic acid (5-HPETE) and that the 10-D (pro-R)-hydrogen is eliminated in the conversion of 5-HPETE into LTA. 

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]. 

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