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Review
. 2022 Mar 19;11(3):590.
doi: 10.3390/antiox11030590.

A PON for All Seasons: Comparing Paraoxonase Enzyme Substrates, Activity and Action including the Role of PON3 in Health and Disease

Chrysan J Mohammed  1 , Sabitri Lamichhane  2 , Jacob A Connolly  1 , Sophia M Soehnlen  1 , Fatimah K Khalaf  1   3 , Deepak Malhotra  1 , Steven T Haller  1 , Dragan Isailovic  2 , David J Kennedy  1
Affiliations
Review

A PON for All Seasons: Comparing Paraoxonase Enzyme Substrates, Activity and Action including the Role of PON3 in Health and Disease

Chrysan J Mohammed et al. Antioxidants (Basel). .

Abstract

Paraoxonases (PONs) are a family of hydrolytic enzymes consisting of three members, PON1, PON2, and PON3, located on human chromosome 7. Identifying the physiological substrates of these enzymes is necessary for the elucidation of their biological roles and to establish their applications in the biomedical field. PON substrates are classified as organophosphates, aryl esters, and lactones based on their structure. While the established native physiological activity of PONs is its lactonase activity, the enzymes' exact physiological substrates continue to be elucidated. All three PONs have antioxidant potential and play an important anti-atherosclerotic role in several diseases including cardiovascular diseases. PON3 is the last member of the family to be discovered and is also the least studied of the three genes. Unlike the other isoforms that have been reviewed extensively, there is a paucity of knowledge regarding PON3. Thus, the current review focuses on PON3 and summarizes the PON substrates, specific activities, kinetic parameters, and their association with cardiovascular as well as other diseases such as HIV and cancer.

Keywords: HIV; cancer; cardiovascular disease; lactones; paraoxonase; substrates.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
PON synthesis in liver and their roles in various diseases (created with Biorender.com (Date when last accessed: 21 February 2022).
Figure 2
Figure 2
Paraoxon hydrolysis reaction for which paraoxonase derives its name [18].
Figure 3
Figure 3
Activities of PONs and their substrates.
Figure 4
Figure 4
Hydrolysis of 5,6-DHETL by PONs [32].
See this image and copyright information in PMC

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