Lipoxygenase reaction, major products

As mentioned earlier, oxidation of LDL is initiated by free radical attack at the diallylic positions of unsaturated fatty acids. For example, copper- or endothelial cell-initiated LDL oxidation resulted in a large formation of monohydroxy derivatives of linoleic and arachi-donic acids at the early stage of the reaction [175], During the reaction, the amount of these products is diminished, and monohydroxy derivatives of oleic acid appeared. Thus, monohydroxy derivatives of unsaturated acids are the major products of the oxidation of human LDL. Breuer et al. [176] measured cholesterol oxidation products (oxysterols) formed during copper- or soybean lipoxygenase-initiated LDL oxidation. They identified chlolcst-5-cnc-3(3, 4a-diol, cholest-5-ene-3(3, 4(3-diol, and cholestane-3 3, 5a, 6a-triol, which are present in human atherosclerotic plaques. 

Garssen et al. 134) observed that soybean lipoxygenase, presumably lipoxygenase-1, acting at pH 9.0 under anaerobic conditions and in the presence of linoleic acid and 13-hydroperoxy octadeca-ci5-9-trans-ll-dienoic acid i.e., the major product formed in the hydroperoxidation of linoleic acid by this enzyme) gives 13-keto-octadeca-9,ll-dienoic acid and the split products, pentane and 13-keto-trideca.-cis trans)-9-trans-ll-dienoic acid. The D-9-hydroperoxy compound cannot substitute for the L-13-hydroperoxide 135). Dimers are also formed under these conditions. These reactions do not occur under aerobic conditions. Two possible pathways for the anaerobic reaction suggested by these workers are shown in Figures 1 and 2. 

Major products of the lipoxygenase reaction are 9- and 13-hydroperoxides of IV and V, VI, VII, VIII and IX. Hydroperoxide lyase utilizes the 9- and/or 13-hydroperoxides (VI, VII, VIII and IX). Based on substrate specificity, hydroperoxide lyase is classified into three types. The first type is 9-hydroperoxide-specific. 

An obvious way to find out about the physiological function of an enzyme is to study the fate of the products that result from the reaction catalysed by the enzyme. The primary products of the lipoxygenase reaction, fatty-acid hydroperoxides, are potentially dangerous and should be quickly metabolized. Two major routes for metabolizing lipoxygenase products have been identified, collectively known as the lipoxygenase pathway [176]. This was recently extended by the discovery of the peroxygenase cascade [177]. 

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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