Document Detail

On the role of molecular oxygen in lipoxygenase activation: comparison and contrast of epidermal lipoxygenase-3 with soybean lipoxygenase-1.
MedLine Citation:
PMID:  20923767     Owner:  NLM     Status:  MEDLINE    
The oxygenation of polyunsaturated fatty acids by lipoxygenases (LOX) is associated with a lag phase during which the resting ferrous enzyme is converted to the active ferric form by reaction with fatty acid hydroperoxide. Epidermal lipoxygenase-3 (eLOX3) is atypical in displaying hydroperoxide isomerase activity with fatty acid hydroperoxides through cycling of the ferrous enzyme. Yet eLOX3 is capable of dioxygenase activity, albeit with a long lag phase and need for high concentrations of hydroperoxide activator. Here, we show that higher O(2) concentration shortens the lag phase in eLOX3, although it reduces the rate of hydroperoxide consumption, effects also associated with an A451G mutation known to affect the disposition of molecular oxygen in the LOX active site. These observations are consistent with a role of O(2) in interrupting hydroperoxide isomerase cycling. Activation of eLOX3, A451G eLOX3, and soybean LOX-1 with 13-hydroperoxy-linoleic acid forms oxygenated end products, which we identified as 9R- and 9S-hydroperoxy-12S,13S-trans-epoxyoctadec-10E-enoic acids. We deduce that activation partly depends on reaction of O(2) with the intermediate of hydroperoxide cleavage, the epoxyallylic radical, giving an epoxyallylic peroxyl radical that does not further react with Fe(III)-OH; instead, it dissociates and leaves the enzyme in the activated free ferric state. eLOX3 differs from soybean LOX-1 in more tightly binding the epoxyallylic radical and having limited access to O(2) within the active site, leading to a deficiency in activation and a dominant hydroperoxide isomerase activity.
Yuxiang Zheng; Alan R Brash
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2010-10-05
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-14     Completed Date:  2011-01-11     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  39876-87     Citation Subset:  IM    
Department of Pharmacology and the Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
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MeSH Terms
Catalytic Domain
Enzyme Activation / genetics
Hydrogen Peroxide / chemistry
Linoleic Acids / chemistry
Lipoxygenase / chemistry*,  genetics,  metabolism
Mutation, Missense
Oxygen / chemistry*,  metabolism
Plant Proteins / chemistry*,  genetics,  metabolism
Soybeans / enzymology*
Species Specificity
Grant Support
Reg. No./Substance:
0/Linoleic Acids; 0/Plant Proteins; 7722-84-1/Hydrogen Peroxide; 7782-44-7/Oxygen; EC protein, human; EC; GO26VC5N5G/13-hydroperoxylinoleic acid

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