Premium
Measurement and diagnostic use of hepatic cytochrome P450 metabolism of oleic acid in liver disease
Author(s) -
Thum Thomas,
Batkai Sandor,
Malinski Philipp G.,
Becker Thomas,
Mevius Iris,
Klempnauer Jürgen,
Meyer Hartmut H.,
Frölich Jürgen C.,
Borlak Jürgen,
Tsikas Dimitrios
Publication year - 2010
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2010.02310.x
Subject(s) - oleic acid , cyp2c8 , cytochrome p450 , cyp3a , liver disease , biomarker , metabolism , medicine , liver function , biochemistry , fatty acid , chemistry , fatty liver , endocrinology , biology , disease , cyp3a4
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.