Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-2-5
pubmed:abstractText
Leukotriene B4 (LTB4) is a potent lipid mediator of the inflammatory response whose biological half-life is believed to be mediated principally by metabolism to inactive forms either in the tissue of origin or in the liver. Pathways of metabolic degradation of LTB4 along with structural identification of metabolites have been elucidated previously in isolated rat liver cells, human keratinocytes, human polymorphonuclear leukocytes, and cultured HepG2 cells. Research advances in human liver transplantation and preservation have made isolated human hepatocytes available for studying the metabolism of LTB4 in vitro. LTB4 was added to plated human hepatocytes from three different subjects for 24-h periods whereupon the substrate was analyzed by high-performance liquid chromatography coupled with scintillation counting, UV spectroscopy, and negative ion electrospray ionization tandem mass spectrometry. Each set of hepatocytes yielded a different distribution of metabolites, but several metabolites appeared in all three sets of cells. These central metabolites included the previously identified 20-carboxy-LTB4 and 18-carboxy-LTB4, implicating the presence in the liver of specific P-450-mediated omega-oxidation as well as the enzymes involved in beta-oxidation from the omega-terminus. Each set of hepatocytes produced the metabolite 10,11-dihydro-20-COOH-LTB4, a product of the 12-hydroxyeicosanoid dehydrogenase/Delta10 reductase pathway. Glucuronides of LTB4 and several metabolites were found, which represents the first description of glucuronidation as a pathway of LTB4 metabolism. Finally, a series of novel metabolites were observed corresponding to beta-oxidation from the carboxyl terminus of LTB4.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
288
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
326-34
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Metabolic transformations of leukotriene B4 in primary cultures of human hepatocytes.
pubmed:affiliation
Department of Pediatrics, Division of Basic Sciences, National Jewish Medical and Research Center, Denver, Colorado, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.