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 journalArticle

6 Citations (Scopus)

Abstract

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
Volume1811
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

Aryldialkylphosphatase
Lactones
Fatty Acids
Serum
Carboxylesterase
HDL Lipoproteins
Edetic Acid
Gel Chromatography
Carbon

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Mouse serum paraoxonase-1 lactonase activity is specific for medium-chain length fatty acid lactones. / Connelly, Philip W.; Picardo, Clive M.; Potter, Philip M.; Teiber, John F.; Maguire, Graham F.; Ng, Dominic S.

In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, Vol. 1811, No. 1, 01.2011, p. 39-45.

Research output: Contribution to journalArticle

Connelly, Philip W. ; Picardo, Clive M. ; Potter, Philip M. ; Teiber, John F. ; Maguire, Graham F. ; Ng, Dominic S. / Mouse serum paraoxonase-1 lactonase activity is specific for medium-chain length fatty acid lactones. In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. 2011 ; Vol. 1811, No. 1. pp. 39-45.
@article{127f0c7fa1104bee965836e921881fb9,
title = "Mouse serum paraoxonase-1 lactonase activity is specific for medium-chain length fatty acid lactones",
abstract = "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.",
keywords = "γ-Lactones, δ-Lactones, Carboxylesterase, ES-1, High-density lipoprotein, Lactonase, Lactone, Mouse serum, Paraoxonase-1",
author = "Connelly, {Philip W.} and Picardo, {Clive M.} and Potter, {Philip M.} and Teiber, {John F.} and Maguire, {Graham F.} and Ng, {Dominic S.}",
year = "2011",
month = "1",
doi = "10.1016/j.bbalip.2010.10.002",
language = "English (US)",
volume = "1811",
pages = "39--45",
journal = "Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids",
issn = "1388-1981",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Mouse serum paraoxonase-1 lactonase activity is specific for medium-chain length fatty acid lactones

AU - Connelly, Philip W.

AU - Picardo, Clive M.

AU - Potter, Philip M.

AU - Teiber, John F.

AU - Maguire, Graham F.

AU - Ng, Dominic S.

PY - 2011/1

Y1 - 2011/1

N2 - 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.

AB - 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.

KW - γ-Lactones

KW - δ-Lactones

KW - Carboxylesterase

KW - ES-1

KW - High-density lipoprotein

KW - Lactonase

KW - Lactone

KW - Mouse serum

KW - Paraoxonase-1

UR - http://www.scopus.com/inward/record.url?scp=78649774614&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78649774614&partnerID=8YFLogxK

U2 - 10.1016/j.bbalip.2010.10.002

DO - 10.1016/j.bbalip.2010.10.002

M3 - Article

C2 - 21044894

AN - SCOPUS:78649774614

VL - 1811

SP - 39

EP - 45

JO - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

JF - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

SN - 1388-1981

IS - 1

ER -