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.

doi:10.1016/j.bbalip.2010.10.002

Cited by 6 publications

(3 citation statements)

References 28 publications

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“…The remaining two isozymes, PON1 and PON3, found in the liver and blood, show lower activity toward HSLs. Their primary substrates seem to be ␦-lactones and/or ␥-lactones with lipophilic side chains (49,50,55).…”

Section: Serum Paraoxonasesmentioning

confidence: 99%

Divergence and Convergence in Enzyme Evolution: Parallel Evolution of Paraoxonases from Quorum-quenching Lactonases

Elias

Tawfik

2012

Journal of Biological Chemistry

115

141

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We discuss the basic features of divergent versus convergent evolution and of the common scenario of parallel evolution. The example of quorum-quenching lactonases is subsequently described. Three different quorum-quenching lactonase families are known, and they belong to three different superfamilies. Their key active-site architectures have converged and are strikingly similar. Curiously, a promiscuous organophosphate hydrolase activity is observed in all three families. We describe the structural and mechanistic features that underline this converged promiscuity and how this promiscuity drove the parallel divergence of organophosphate hydrolases within these lactonase families by either natural or laboratory evolution.

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Section: Serum Paraoxonasesmentioning

confidence: 99%

Divergence and Convergence in Enzyme Evolution: Parallel Evolution of Paraoxonases from Quorum-quenching Lactonases

Elias

Tawfik

2012

Journal of Biological Chemistry

115

141

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“…They hydrolyze a wide range of ␦-and ␥-lactones with lipophilic side chains (fatty acid lactones or lipolactones; Fig. 1 (4,21). PON1 and PON3 also hydrolyze the quorum-sensing lactone 3OC12-HSL, yet with much lower efficiency (17).…”

mentioning

confidence: 99%

The Evolutionary Origins of Detoxifying Enzymes

Hagit

Hugenmatter

Tawfik

2013

Journal of Biological Chemistry

115

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Background: Serum paraoxonases (PONs) comprise a family of mammalian detoxifying lactonases with different substrate specificities. Results: A newly identified bacterial PON and the reconstructed ancestor of mammalian PONs are quorum-quenching lactonases. Conclusion: PONs originated from quorum-quenching lactonases that later acquired new detoxifying functions. Significance: The evolutionary history of detoxifying enzymes may explain their ambiguous and overlapping specificity profiles.

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“…Paraoxonase 1 (PON1) is a calcium-dependent esterase synthesized in the liver and circulating in the blood attached to high-density lipoproteins (HDL). PON1 protects plasma lipoproteins including low-density lipoproteins (LDL) and HDL themselves from oxidative modification by decomposing lipid peroxidation products such as fatty acid lactones [ 6 ]. In addition, PON1 hydrolyzes homocysteine (Hcy) thiolactone both in vitro [ 7 ] and in vivo [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Paraoxonase 1 Phenotype and Protein N-Homocysteinylation in Patients with Rheumatoid Arthritis: Implications for Cardiovascular Disease

2020

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Paraoxonase 1 (PON1) is the high density lipoprotein-associated esterase which inhibits the development of atherosclerosis by metabolizing lipid peroxidation products as well as hydrolyzing proatherogenic metabolite of homocysteine (Hcy), Hcy thiolactone, which otherwise reacts with lysine groups of proteins, thus forming N-Hcy-protein in a process referred to as protein N-homocysteinylation. Rheumatoid arthritis (RA) is the chronic inflammatory autoimmune disease associated with increased risk of cardiovascular complications, but the underlying mechanisms are incompletely understood. We examined PON1 status and N-homocysteinylation of serum proteins in patients with RA. Blood was collected from 74 RA patients and 70 control subjects. PON1 activity was measured toward synthetic (paraoxon, phenyl acetate) and natural (Hcy thiolactone) substrates. PON1 protein concentration was measured by ELISA. Total Hcy as well as N-Hcy-protein were measured in serum as well. PON1 activity toward Hcy thiolactone was lower in RA patients than in control subjects which was accompanied by increased concentration of N-Hcy-protein despite normal total Hcy concentration. PON1 protein concentration was unchanged in the RA group, but the specific enzyme activity was reduced. When RA patients were categorized according to the DAS28-ESR score, PON1 concentration and enzymatic activity were lower whereas N-Hcy-protein was higher in those with high disease activity. PON1 activity and Hcy thiolactone were correlated with DAS28-ESR score and myeloperoxidase concentration. In conclusion, RA is associated with deficiency of PON1 activity and increased protein N-homocyseinylation which may contribute to accelerated development of cardiovascular diseases.

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

Cited by 6 publications

References 28 publications

Divergence and Convergence in Enzyme Evolution: Parallel Evolution of Paraoxonases from Quorum-quenching Lactonases

Divergence and Convergence in Enzyme Evolution: Parallel Evolution of Paraoxonases from Quorum-quenching Lactonases

The Evolutionary Origins of Detoxifying Enzymes

Paraoxonase 1 Phenotype and Protein N-Homocysteinylation in Patients with Rheumatoid Arthritis: Implications for Cardiovascular Disease

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