| First Author | Connelly PW | Year | 2011 |
| Journal | Biochim Biophys Acta | Volume | 1811 |
| Issue | 1 | Pages | 39-45 |
| PubMed ID | 21044894 | Mgi Jnum | J:170288 |
| Mgi Id | MGI:4946182 | Doi | 10.1016/j.bbalip.2010.10.002 |
| Citation | Connelly PW, et al. (2011) Mouse serum paraoxonase-1 lactonase activity is specific for medium-chain length fatty acid lactones. Biochim Biophys Acta 1811(1):39-45 |
| abstractText | 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 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. |
