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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1989-7-3
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pubmed:abstractText |
1. The cytochrome P-450-dependent metabolism of leukotriene B4 (LTB4) by rat hepatic microsomes was characterized. Hepatic microsomes were found to metabolize LTB4 to 20-hydroxy-LTB4 and 20-carboxy:LTB4. The rate of formation of 20-hydroxy-LTB4 (14.6 pmol/min per mg protein) was 5.8-fold higher than that of 20-carboxy-LTB4 (2.5 pmol/min per mg protein). 2. LTB4 omega-hydroxylase activity required NADPH and oxygen indicating that the reaction is mediated by a mono-oxygenase system. The omega-hydroxylase activity was optimal at pH 7.4 and product formation was linear with respect to time of incubation and protein concentration. The reaction was significantly inhibited by carbon monoxide (89%), SKF 525-A (1 mM), and metyrapone (0.1 mM) whereas alpha-naphthoflavone had only marginal inhibitory effects. The apparent Km and Vmax of LTB4 omega-hydroxylase were 4 microM and 19.6 pmol/min per mg protein, respectively. 3. Ontogenic studies revealed that LTB4 omega-hydroxylase activity was low in 4-day-old rats and that there was a steady increase in enzyme activity as the animal matured. 4. Phenobarbital, 3-methylcholanthrene or Aroclor 1254 treatment of rats did not induce LTB4 omega-hydroxylase activity whereas clofibrate resulted in 61% induction in enzyme activity. No significant sex-dependent differences were observed. 5. It is concluded that hepatic metabolism of LTB4 may afford an effective mechanism for limiting many of the pro-inflammatory effects of circulating leukotrienes.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/20-carboxyleukotriene B4,
http://linkedlifedata.com/resource/pubmed/chemical/5,12,20-trihydroxy-6,8,10,14-eicosat...,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyeicosatetraenoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Leukotriene B4,
http://linkedlifedata.com/resource/pubmed/chemical/Mixed Function Oxygenases,
http://linkedlifedata.com/resource/pubmed/chemical/NADP,
http://linkedlifedata.com/resource/pubmed/chemical/Tritium,
http://linkedlifedata.com/resource/pubmed/chemical/leukotriene B4 20-hydroxylase
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0049-8254
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
151-9
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:2543147-Aging,
pubmed-meshheading:2543147-Animals,
pubmed-meshheading:2543147-Biotransformation,
pubmed-meshheading:2543147-Chromatography, High Pressure Liquid,
pubmed-meshheading:2543147-Cytochrome P-450 Enzyme System,
pubmed-meshheading:2543147-Enzyme Repression,
pubmed-meshheading:2543147-Female,
pubmed-meshheading:2543147-Hydroxyeicosatetraenoic Acids,
pubmed-meshheading:2543147-Kinetics,
pubmed-meshheading:2543147-Leukotriene B4,
pubmed-meshheading:2543147-Microsomes, Liver,
pubmed-meshheading:2543147-Mixed Function Oxygenases,
pubmed-meshheading:2543147-NADP,
pubmed-meshheading:2543147-Pregnancy,
pubmed-meshheading:2543147-Rats,
pubmed-meshheading:2543147-Sex Factors,
pubmed-meshheading:2543147-Tritium
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pubmed:year |
1989
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pubmed:articleTitle |
Hepatic microsomal metabolism of leukotriene B4 in rats: biochemical characterization, effect of inducers, and age- and sex-dependent differences.
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pubmed:affiliation |
Department of Dermatology, University Hospital of Cleveland, Case Western Reserve University, Ohio.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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