Wednesday, September 11, 2013

Sarin Gas

If you haven't checked out SciShow on Youtube yet, please do yourself this favour. Consisting of quick science related videos it is accessible, entertaining and surprisingly informative. The SciShow team have a pretty good time with the material, probably best evidenced by the recent "Is SHARKNADO Possible?"
A recent SciShow describes some basic facts about Sarin gas, the nerve agent that recently killed hundreds of Syrian civilians. The video describes Sarin as an inhibitor of acetylcholinesterase. Sarin's inhibition of this enzyme prevents removal of actylecholine from neuromuscular junctions resulting in continuously contracting muscles and death from asphyxia due to the inability to control the muscles involved in breathing function.
Interestingly there are antidotes for sarin gas exposure and the resulting irreversible inhibition of acetylcholinesterase. Some antidotes simply inhibit acetylcholine receptors preventing the action of the accumulated acetylcholine and are themselves a poison. However pralidoxime (2-pyridine aldoxime methyl chloride,) or 2-PAM actually restores function to the irreversibly inhibited enzyme. It reacts with organophosphorus nerve agents such as sarin and reverses the covalent bond to the serine in the active site of acetylcholinesterase resulting in a reactivated enzyme. I have never heard of such an antidote or reaction. While I guess it is comforting to think there are antidotes to these weapons they are largely impractical due to the time frame in which they must be administered.
Are there any other examples of molecules that can reverse the irreversible inhibition of an enzyme?