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Mammalian 15-Lipoxygenases

Enzymatic Properties and Biological Implications

  • Chapter
Book cover Lipoxygenases and their Metabolites

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 447))

Abstract

Lipoxygenases are enzymes which dioxygenate polyunsaturated fatty acids to hydroperoxy derivatives. Although the mechanism of the enzyme catalysis is not entirely clear, it has been suggested that the lipoxygenase reaction involves the formation of an enzyme-bound fatty acid radical which is formed via a stereoselective removal of a hydrogen from a doubly allylic methylene group.1 It should be stressed that there are alternative explanations of the reaction mechanism implicating an electron removal from a double bond forming a fatty acid cation and a subsequent abstraction of a proton which would require a strong basic residue at the active site of the enzyme.2 Assuming the radical mechanism, the lipoxygenase reaction resembles that of the non-enzymatic lipid peroxidation. In principle, both reactions can be divided into three steps (Figure 1): i) hydrogen abstraction, ii) radical rearrangement and iii) oxygen insertion. During the lipoxygenase reaction each of the three steps is enzyme-controlled which leads to a specific pattern of oxygenation products. If, for instance, more than one doubly allylic methylene is present in the substrate fatty acid, lipoxygenases select one of them for initial hydrogen abstraction.3 In contrast, during non-enzymatic lipid peroxidation, hydrogen is removed from all doubly allylic methylenes. Similarly, the introduction of dioxygen proceeds stereoselectively in the case of the lipoxygenase reaction, whereas a stereorandom oxygenation is observed for the non-enzymatic lipid peroxidation.

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  1. Institute of Biochemistry, University Clinics Charité, Humboldt University of Berlin, Hessische Str. 3-4, D-10115, Berlin, Germany

    Hartmut Kühn & Sabine Borngräber

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  1. Hartmut Kühn
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  1. Free University of Berlin, Berlin, Germany

    Santosh Nigam

  2. Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

    Cecil R. Pace-Asciak

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© 1999 Kluwer Academic/Plenum Publishers, New York

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Kühn, H., Borngräber, S. (1999). Mammalian 15-Lipoxygenases. In: Nigam, S., Pace-Asciak, C.R. (eds) Lipoxygenases and their Metabolites. Advances in Experimental Medicine and Biology, vol 447. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4861-4_2

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  • DOI: https://doi.org/10.1007/978-1-4615-4861-4_2

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