Efficient hydrolysis of the chemical warfare nerve agent tabun by recombinant and purified human and rabbit serum paraoxonase 1.
Paraoxonase 1 (PON1) has been described as an efficient catalytic bioscavenger due to its ability to hydrolyze organophosphates (OPs) and chemical warfare nerve agents (CWNAs). It is the future most promising candidate as prophylactic medical countermeasure against highly toxic OPs and CWNAs. Most of the studies conducted so far have been focused on the hydrolyzing potential of PON1 against nerve agents, sarin, soman, and VX. Here, we investigated the hydrolysis of tabun by PON1 with the objective of comparing the hydrolysis potential of human and rabbit serum purified and recombinant human PON1. The hydrolysis potential of PON1 against tabun, sarin, and soman was evaluated by using an acetylcholinesterase (AChE) back-titration Ellman method. Efficient hydrolysis of tabun (100 nM) was observed with ∼25-40 mU of PON1, while higher concentration (80-250 mU) of the enzyme was required for the complete hydrolysis of sarin (11 nM) and soman (3 nM). Our data indicate that tabun hydrolysis with PON1 was ∼30-60 times and ∼200-260 times more efficient than that with sarin and soman, respectively. Moreover, the catalytic activity of PON1 varies from source to source, which also reflects their efficiency of hydrolyzing different types of nerve agents. Thus, efficient hydrolysis of tabun by PON1 suggests its promising potential as a prophylactic treatment against tabun exposure.
Closed Head Injury Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. m.valiyaveettil@amedd.army.mil
Manojkumar
M
Valiyaveettil
Yonas
Y
Alamneh
Lionel
L
Biggemann
Iswarduth
I
Soojhawon
Bhupendra P
BP
Doctor
Madhusoodana P
MP
Nambiar
D000818:Animals; D043303:Aryldialkylphosphatase / Q000378:metabolism*; D002619:Chemical Warfare Agents / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D009420:Nervous System / Q000187:drug effects*; D010755:Organophosphates / Q000378:metabolism*; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism
D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D010755:Organophosphates; D011994:Recombinant Proteins; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; C009374:tabun