Measurement and diagnostic use of hepatic cytochrome P450 metabolism of oleic acid in liver disease.
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.
Thum
Thomas
T
Institute for Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany. thum.thomas@mh-hannover.de
Batkai
Sandor
S
Malinski
Philipp G
PG
Becker
Thomas
T
Mevius
Iris
I
Klempnauer
Jürgen
J
Meyer
Hartmut H
HH
Frölich
Jürgen C
JC
Borlak
Jürgen
J
Tsikas
Dimitrios
D
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
D015415:Biomarkers; D013229:Stearic Acids; D019301:Oleic Acid; D003577:Cytochrome P-450 Enzyme System