Hydroperoxy-eicosatetraenoic acid derivatives

This reaction was amrmg the earliest used for the GLC resolution of enantiomeric alcohols Studies 20 years ago showed that the reaction of (—)-menthyI chloroformate, [17], with chiral alcohols produced dia-stereomeric carbonates that could be resolved on packed columns (71,162). Despite its commercial availability, this CDA has been little used for the resolution of alcohols, Prelusky et al. (163) used [17] in a study of enantio-selecrive metabolic ketone reductions. The metabolite alcohols were deri-vatized with [17] and the derivatives were separated by capillary GLC. Good resolution was obtained under the chromatographic conditions used (163). The derivatization of warfarin with [17] and LC of the derivatives was described, but the peaks were not fully separated, even with retention times of 80-100 min (164). Brash et al. used CDA [17] to determine the enantiomeric composition of several enantiomeric pairs of hydroperoxy-eicosatetraenoic acids using silica LC, but some of the derivatives could not be resolved (165). It appears that [17] may be useful in the resolution of hydroxyl compounds and the evaluation of capillary GLC in the separations deserves attention. 

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... 

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]. 

This enzyme is found in the cytosol of rabbit peritoneal polymorphonuclear leukocytes and can be purified about 250-fold. The reaction product from arachidonic acid is 15-hydroperoxy-5,8,l 1,13-eicosatetraenoic acid which undergoes non-en-zymatic degradation to 15-hydroxy-, 15-keto-, 13-hydroxy-14,15-epoxy- and 11,14,15-trihydroxy derivatives [211]. 

A unique lipoxygenase was isolated and purified from rabbit reticulocytes [212], The purified enzyme with a molecular weight of 78000 contains two moles of iron per enzyme molecule. The enzyme is identical with the previously known protein factors which inhibit the respiratory chain. The purified lipoxygenase causes a loss of acid-labile sulfur from mitochondrial electron transfer particles and acts preferably on the mitochondrial membrane. The enzyme is considered to work in the lysis of mitochondria during the maturation of erythrocytes. The major product from arachidonic acid is 15S-hydroperoxy-5,8,l 1,13-eicosatetraenoic acid, although the 12S-hydroperoxy derivative is produced as a minor product [213]. 

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