Source:http://linkedlifedata.com/resource/pubmed/id/15544336
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
46
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| pubmed:dateCreated |
2004-11-16
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| pubmed:abstractText |
Mammalian 5-lipoxygenase (5-LO) catalyzes the conversion of arachidonic acid (AA) to leukotrienes, potent inflammatory mediators. 5-LO is activated by a Ca(2+)-mediated translocation to membranes, and demonstrates the characteristic features of interfacially activated enzymes, yet the mechanism of membrane binding of 5-LO is not well understood. In an attempt to understand the mechanism of lipid-mediated activation of 5-LO, we have studied the effects of a large set of lipids on human recombinant 5-LO activity, as well as mutual structural effects of 5-LO and membranes. In the presence of 0.35 mM phosphatidylcholine (PC) and 0.2 mM Ca(2+), there was substrate inhibition at >100 microM AA. Data analysis at low AA concentrations yielded the following: K(m) approximately 103 microM and k(cat) approximately 56 s(-1). 5-LO activity was supported by PC more than by any other lipid tested except for a cationic lipid, which was more stimulatory than PC. Binding of 5-LO to zwitterionic and acidic membranes was relatively weak; the extent of binding increased 4-8 times in the presence of Ca(2+), whereas binding to cationic membranes was stronger and essentially Ca(2+)-independent. Polarized attenuated total reflection infrared experiments implied that 5-LO binds to membranes at a defined orientation with the symmetry axis of the putative N-terminal beta-barrel tilted approximately 45 degrees from the membrane normal. Furthermore, membrane binding of 5-LO resulted in dehydration of the membrane surface and was paralleled with stabilization of the structures of both 5-LO and the membrane. Our results provide insight into the understanding of the effects of membrane surface properties on 5-LO-membrane interactions and the interfacial activation of 5-LO.
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| pubmed:grant | |
| pubmed:commentsCorrections | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-palmitoyl-2-oleoylphosphatidylchol...,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonate 5-Lipoxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cations, Divalent,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Diglycerides,
http://linkedlifedata.com/resource/pubmed/chemical/Glycerides,
http://linkedlifedata.com/resource/pubmed/chemical/Lipid Bilayers,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Lipids,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylcholines,
http://linkedlifedata.com/resource/pubmed/chemical/Quaternary Ammonium Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Sphingolipids,
http://linkedlifedata.com/resource/pubmed/chemical/zwittergent 3-12
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
0006-2960
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
23
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| pubmed:volume |
43
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
14653-66
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:15544336-Arachidonate 5-Lipoxygenase,
pubmed-meshheading:15544336-Calcium,
pubmed-meshheading:15544336-Cations, Divalent,
pubmed-meshheading:15544336-Cholesterol,
pubmed-meshheading:15544336-Diglycerides,
pubmed-meshheading:15544336-Enzyme Activation,
pubmed-meshheading:15544336-Glycerides,
pubmed-meshheading:15544336-Humans,
pubmed-meshheading:15544336-Intracellular Membranes,
pubmed-meshheading:15544336-Kinetics,
pubmed-meshheading:15544336-Lipid Bilayers,
pubmed-meshheading:15544336-Membrane Lipids,
pubmed-meshheading:15544336-Models, Chemical,
pubmed-meshheading:15544336-Phosphatidylcholines,
pubmed-meshheading:15544336-Quaternary Ammonium Compounds,
pubmed-meshheading:15544336-Spectroscopy, Fourier Transform Infrared,
pubmed-meshheading:15544336-Sphingolipids,
pubmed-meshheading:15544336-Static Electricity,
pubmed-meshheading:15544336-Surface Properties
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| pubmed:year |
2004
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| pubmed:articleTitle |
Modulation of human 5-lipoxygenase activity by membrane lipids.
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| pubmed:affiliation |
Biomolecular Science Center, University of Central Florida, Orlando, Florida 32826, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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