title: Measurement and diagnostic use of hepatic cytochrome P450 metabolism of oleic acid in liver disease.
abstract: BACKGROUND
  Oleic acid is a major systemically circulating fatty acid in humans with atheroprotective and immunomodulatory properties. As of today, the contribution of individual cytochrome P450 (CYP) mono-oxygenases to the epoxidation of this fatty acid is unknown. Furthermore, the extent of the oleic acid oxidation product cis-9,10-epoxyoctadecanoic acid (cis-EODA) in humans and its plasma levels in patients with impaired liver function are not known.
  
  
  METHODS
  We studied cis-EODA in plasma of patients suffering from chronic liver diseases, a condition that often displays impaired liver CYP enzyme activities. Fifteen CYP mono-oxygenases were investigated in vitro as a potential source of cis-EODA.
  
  
  RESULTS
  Strikingly, plasma levels of cis-EODA were significantly repressed (P<0.0005) when patients with liver impairment (n=16) were compared with healthy subjects (n=14). Production of cis-EODA was catalysed by CYP in the following order: 2C8, 2C9, 2C19, 3A4, 1A2 and CYP3A7.
  
  
  CONCLUSIONS
  cis-EODA plasma concentrations are decreased in hepatic disease with impaired liver function. Oleic acid is primarily oxidized to oleic acid oxide (cis-EODA) by CYP2C and CYP3A mono-oxygenases. The liver is the major organ responsible for the oxidation of oleic acid to cis-EODA, and thus, cis-EODA may be a suitable biomarker to assess liver function.
authors.affiliation: Institute for Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany. thum.thomas@mh-hannover.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Thum
authors.forename: Sandor
authors.initials: S
authors.lastname: Batkai
authors.forename: Philipp G
authors.initials: PG
authors.lastname: Malinski
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
authors.forename: Iris
authors.initials: I
authors.lastname: Mevius
authors.forename: Jürgen
authors.initials: J
authors.lastname: Klempnauer
authors.forename: Hartmut H
authors.initials: HH
authors.lastname: Meyer
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Frölich
authors.forename: Jürgen
authors.initials: J
authors.lastname: Borlak
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tsikas
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008107:Liver Diseases / Q000175:diagnosis* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D019301:Oleic Acid / Q000097:blood / Q000378:metabolism*; D013229:Stearic Acids / Q000097:blood
chemical_list: D015415:Biomarkers; D013229:Stearic Acids; D019301:Oleic Acid; D003577:Cytochrome P-450 Enzyme System