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Measurement and diagnostic use of hepatic cytochrome P450 metabolism of oleic acid in liver disease

 
: Thum, T.; Batkai, S.; Malinski, P.G.; Becker, T.; Mevius, I.; Klempnauer, J.; Meyer, H.H.; Frölich, J.C.; Borlak, J.; Tsikas, D.

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Liver international 30 (2010), No.8, pp.1181-1188
ISSN: 1478-3223
ISSN: 1478-3231
English
Journal Article
Fraunhofer ITEM ()
chronic liver disease; cirrhosis; CYP2C8; 2C9; 1A2; 2C19; 3A4; 3A7; Cytochrome P-450; epoxidation; Hepatitis C; tandem mass spctrometry; oleic acid; gas chromatography

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.
Patients and 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.
Conclusion: 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.

: http://publica.fraunhofer.de/documents/N-142791.html