Mouse serum paraoxonase-1 lactonase activity is specific for medium-chain length fatty acid lactones

Philip W. Connelly, Clive M. Picardo, Philip M. Potter, John F. Teiber, Graham F. Maguire, Dominic S. Ng

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Recent studies suggest that paraoxonase-1 (PON1), complexed with high-density lipoproteins, is the major lactonase in the circulation. Using 5-hydroxy eicosatetraenoate δ-lactone (5-HETEL) as the substrate, we observed lactonase activity in serum from Pon1-/- mice. However, 6-12 carbon fatty acid γ- and δ-lactones were not hydrolyzed in serum from Pon1-/- mice. Serum from both wild-type and 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.

Original languageEnglish (US)
Pages (from-to)39-45
Number of pages7
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Issue number1
StatePublished - Jan 2011


  • Carboxylesterase
  • ES-1
  • High-density lipoprotein
  • Lactonase
  • Lactone
  • Mouse serum
  • Paraoxonase-1
  • γ-Lactones
  • δ-Lactones

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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