Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
Volume 1811, Issue 1, Pages 39-45Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2010.10.002
Keywords
Paraoxonase-1; Carboxylesterase; Lactone; Lactonase; High-density lipoprotein; ES-1; Mouse serum; delta-Lactones; gamma-Lactones
Funding
- Heart and Stroke Foundation of Ontario [T6389]
- St. Jude Children's Research Hospital
- American Lebanese Syrian Associated Charities (ALSAC)
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Recent studies suggest that paraoxonase-1 (PON1), complexed with high-density lipoproteins, is the major lactonase in the circulation. Using 5-hydroxy eicosatetraenoate delta-lactone (5-HETEL) as the substrate, we observed lactonase activity in serum from Pon1-/- mice. However, 6-12 carbon fatty acid gamma- and delta-lactones were not hydrolyzed in serum from Pon1-/- mice. Serum from both wild-type add Pon1-/- mice contained a lactonase activity towards 5-HETEL and 3-oxo-dodecanoyl-homoserine lactone that was resistant to inactivation by EDTA. This lactonase activity was sensitive to the serine esterase inhibitor phenyl methyl sulfonyl fluoride and co-eluted with carboxylesterase activity by size-exclusion chromatography. Analysis of serum from the Es1e mouse strain, which has a deficiency in the carboxylesterase, ES-1, proved that this activity was due to ES-1. PON1 activity predominated at early time points (30 s), whereas both PON1 and ES-1 contributed equally at later time points (15 min). When both PON1 and ES-1 were inhibited, 5-HETEL was stable in mouse serum. Thus, while long-chain fatty acid lactones are substrates for PON1, they can be hydrolyzed by ES-1 at neutral pH. In contrast, medium-chain length fatty acid lactones are stable in mouse serum in the absence of PON1, suggesting that PON1 plays a specific role in the metabolism of these compounds. (C) 2010 Elsevier B.V. All rights reserved.
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