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Identification of biologically active δ-lactone eicosanoids as paraoxonase substrates.

A new interesting article has been published in Biochem Biophys Res Commun. 2018 Oct 20;505(1):87-92. doi: 10.1016/j.bbrc.2018.09.083. Epub 2018 Sep 18. and titled:

Identification of biologically active δ-lactone eicosanoids as paraoxonase substrates.

Authors of this article are:

Teiber JF, Xiao J, Kramer GL, Ogawa S, Ebner C, Wolleb H, Carreira EM, Shih DM, Haley RW.

A summary of the article is shown below:

The mammalian paraoxonases (PONs 1, 2 and 3) are a family of esterases that are highly conserved within and between species. They exhibit antioxidant and anti-inflammatory activities. However, their physiological function(s) and native substrates are uncertain. Previous structure-activity relationship studies demonstrate that PONs have a high specificity for lipophilic lactones, suggesting that such compounds may be representative of native substrates. This report describes the ability of PONs to hydrolyze two bioactive δ-lactones derived from arachidonic acid, 5,6-dihydroxy-eicosatrienoic acid lactone (5,6-DHTL) and cyclo-epoxycyclopentenone (cyclo-EC). Both lactones were very efficiently hydrolyzed by purified PON3. PON1 efficiently hydrolyzed 5,6-DHTL, but with a specific activity about 15-fold lower than PON3. 5,6-DHTL was a poor substrate for PON2. Cyclo-EC was a poor substrate for PON1 and not hydrolyzed by PON2. Studies with the PON inhibitor EDTA and a serine esterase inhibitor indicated that the PONs are the main contributors to hydrolysis of the lactones in human and mouse liver homogenates. Studies with homogenates from PON3 knockout mouse livers indicated that >80% of the 5,6-DHTL and cyclo-EC lactonase activities were attributed to PON3. The findings provide further insight into the structural requirements for PONs substrates and support the hypothesis that PONs, particularly PON1 and PON3, evolved to hydrolyze and regulate a class of lactone lipid mediators derived from polyunsaturated fatty acids.

Check out the article’s website on Pubmed for more information:



This article is a good source of information and a good way to become familiar with topics such as:

Eicosanoid;Esterase;Isoprostanes;Lactone;Paraoxonase

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