Lipoxygenase specificity

Table III. Effect of a lipoxygenase-specific inhibitor on the occurrence of enzymically- and oxidatively-derived volatiles in fish.

Applications of peroxide formation are underrepresented in chiral synthetic chemistry, most likely owing to the limited stability of such intermediates. Lipoxygenases, as prototype biocatalysts for such reactions, display rather limited substrate specificity. However, interesting functionalizations at allylic positions of unsaturated fatty acids can be realized in high regio- and stereoselectivity, when the enzymatic oxidation is coupled to a chemical or enzymatic reduction process. While early work focused on derivatives of arachidonic acid chemical modifications to the carboxylate moiety are possible, provided that a sufficiently hydrophilic functionality remained. By means of this strategy, chiral diendiols are accessible after hydroperoxide reduction (Scheme 9.12) [103,104]. 

The biological membranes that surround cells and form the boundaries of intracellular organelles contain polyunsaturated fiitty acids, which are susceptible to oxidation. This reaction is used under controlled conditions by enzymes, such as the lipoxygenases or cyclooxygenases, within cells to produce oxygenated lipids, which can act as mediators of inflammation (Smith and Marnett, 1991 Yamamoto, 1992). Such compounds are characterized by their high potency and specificity in their interaction with cells (Salmon, 1986). While these enzymatic reactions... 

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). 

Kausch KD, Handa AK. Molecular cloning of a ripening-specific lipoxygenase and its expression during wild-type and mutant tomato fruit development. Plant Physiol 1997 113 1041-1050. 

Christopher, J. P., Pistorius, E. K., Regnier, F. E., Axelrod, B. Factors influencing the positional specificity of soy bean lipoxygenase. Biochim. Biophys. Acta 289, 82-87 (1972). 

Lipoxygenase [EC 1.13.11.12] catalyzes the reaction of linoleate with dioxygen to produce (9Z,11 )-(135 )-13-hydroperoxyoctadeca-9,ll-dienoate. This iron-depen-dent enzyme can also oxidize other methylene-interrupted polyunsaturated fatty acids. See also specific enzyme... 

Pharmacology Zileuton is a specific inhibitor of 5-lipoxygenase and thus inhibits leukotriene (LTB-i, LTC-, LTD-], LTe- ) formation. 

Royo, J., Vancanneyt, G., Perez, A. G., Sanz, C., Stormann, K., Rosahl, S., Sanchez-Serrano, J. J. (1996). Char-aeterization of three potato lipoxygenases with distinct enzymatic activities and different organ-specific and wound-regulated expression patterns. J. Biol. Chem., 271, 21012-21019. 

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