|LETTER TO THE EDITOR
|Ahead of print publication
Paraoxonase and arylesterase are the same enzyme in humans
Avenida Principe D'Espanya, Miami Playa 43892, Spain
|Date of Submission||17-Sep-2018|
|Date of Acceptance||16-Jan-2019|
|Date of Web Publication||29-Jan-2020|
Avenida Principe D'Espanya, Miami Playa 43892
Source of Support: None, Conflict of Interest: None
I have read with some concern the paper of Okuturlar et al. recently published in your journal. In the introduction, the authors state “Human serum PON and arylesterase (ARE) are both esterase enzymes that have lipophilic antioxidant characteristics. Serum PON acts in conjunction with ARE to function as a single enzyme.” Unfortunately, these two sentences contain a number of misconceptions about paraoxonase which appear to be particularly prevalent in the Turkish medical research community. The same misconceptions are present in several other papers published this year by Turkish researchers, leading to questions regarding the expertise of the reviewers of these manuscripts.
Human serum contains a single enzyme (one gene product) responsible for the hydrolysis of both paraoxon (paraoxonase [PON]) and phenylacetate (arylesterase [ARE]), which were the substrates used by Okuturlar et al., as elegantly described by Karen Gan and Bert La Du in 1991 and subsequently confirmed at the biochemical, molecular biological, and molecular genetic levels; this enzyme is paraoxonase 1 (PON1), which used to be called serum PON/ARE to illustrate the fact that a single enzyme was responsible for the hydrolysis of both substrates.
Although its natural substrates are probably lipolactones, PON1 is a highly promiscuous enzyme and will hydrolyze a large variety of lactones, thiolactones, organophosphorus triester pesticides and nerve gasses (paraoxon, diazoxon, sarin, and soman to name a few), aryl esters, estrogen esters, cyclic carbamates, and glucuronide drugs. These basic facts on PON1 have been known for some years, and it is vitally important that misinterpretations of these facts are challenged, preferably by reviewers before manuscripts are published.
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Conflicts of interest
There are no conflicts of interest.
| > References|| |
Okuturlar Y, Gunaldi M, Kocoglu H, Hursitoglu M, Gedikbasi A, Acarer D, et al.
Serum paraoxonase and arylesterase can be useful markers to predict neoadjuvant chemotherapy requirement in patients with breast cancer. J Cancer Res Ther 2018;14:S362-7.
Gan KN, Smolen A, Eckerson HW, La Du BN. Purification of human serum paraoxonase/arylesterase. Evidence for one esterase catalyzing both activities. Drug Metab Dispos 1991;19:100-6.
Mackness M, Mackness B. Human paraoxonase-1 (PON1): Gene structure and expression, promiscuous activities and multiple physiological roles. Gene 2015;567:12-21.
Draganov DI, Teiber JF, Speelman A, Osawa Y, Sunahara R, La Du BN, et al.
Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. J Lipid Res 2005;46:1239-47.
Rajkovic MG, Rumora L, Barisic K. The paraoxonase 1, 2 and 3 in humans. Biochem Med (Zagreb) 2011;21:122-30.