Enzymes human 15-lipoxygenase

Lipoxygenases catalyse the regio-specific and stereoselective oxygenation of unsaturated fatty acids. The mammalian enzymes have been detected in human platelets, lung, kidney, testes and white blood cells. The leukotrienes, derived from the enzymatic action of the enzyme on arachidonic acid, have effects on neutrophil migration and aggregation, release of lysosomal enzymes, capillary permeability, induction of pain and smooth muscle contraction (Salmon, 1986). 

In addition to the aforementioned allenic steroids, prostaglandins, amino acids and nucleoside analogs, a number of other functionalized allenes have been employed (albeit with limited success) in enzyme inhibition (Scheme 18.56) [154-159]. Thus, the 7-vinylidenecephalosporin 164 and related allenes did not show the expected activity as inhibitors of human leukocyte elastase, but a weak inhibition of porcine pancreas elastase [156], Similarly disappointing were the immunosuppressive activity of the allenic mycophenolic acid derivative 165 [157] and the inhibition of 12-lipoxygenase by the carboxylic acid 166 [158]. In contrast, the carboxyallenyl phosphate 167 turned out to be a potent inhibitor of phosphoenolpyruvate carboxylase and pyruvate kinase [159]. Hydrolysis of this allenic phosphate probably leads to 2-oxobut-3-enoate, which then undergoes an irreversible Michael addition with suitable nucleophilic side chains of the enzyme. 

Many other plant enzymes (e.g., lipoxygenases, peroxidases, and oxidases) are able to convert their substrates to more biologically active molecules (e.g., aldehydes, peroxides, epoxides 59,60), which may disrupt insect sensory perception and/or metabolism. However, these enzymes can also depreciate the quality of food so that it is toxic or undesirable to animal and human consumers (12,61), so the application of these enzymes to insect and/or disease resistance is not straightforward. 

Lipoxygenases (LOX) constitute a family of lipid peroxidizing enzymes, which are distributed widely in the plant and animal kingdoms. These enzymes preferentially metabolize substrates that are polyunsaturated fatty acids containing a series of cis double bonds, which are the essential fatty acids for human beings (Kuhn Thiele, 1999). Lipoxygenases are dioxygenases in nature and... 

Chen X-S, Funk CD. Structure-function properties of human platelet 12-lipoxygenase Chimeric enzyme and in vitro mutagenesis studies. FASEB J. 7 (1993) 694-701. 

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