Wednesday, December 5, 2012

Que Sarin, Sarin

Sarin is in the news, or should I say Syrian sarin is in the news. Odd how only that event struck my interest and how quickly I can see its insidious nature.

Sarin blocks an important enzyme which hydrolyzes esters. When I look at its structure, I see the makings of a transition-state analog for the hydrolysis of a carboxylic acid ester:


For non-chemists, let me try and explain what I'm seeing without dumbing it down.

An enzyme catalyzes a simple displacement reaction:

A—B   +  C   --->    A—C  +  B

Think of a couple divorcing or swapping partners. A begins bonded to B but winds up bonded to C and B is freed from bondage to A.  A is the central player--always bound to at least one other. Now there is a crucial moment (not shown but implicit in the reaction arrow, -->) when A simultaneously binds to both B and C; it's the unstable moment before A fully lets go of B to fully clutch C. It's an ephemeral moment or "state," requiring A to partially bind one more atom than it's used to doing: B--A--C has an awkward, fleeting existence. Because A ultimately binds C more strongly than B, A will momentarily contort "uphill" to ultimately wind up more stable with C.

The enzyme's job (or more generically, the catalyst's job) is to stabilize the awkwardness of the transition state: B--A--C. In the divorcing or partner swapping analogy, the social milieu, (acceptance, enablement) will facilitate the transition. In the absence of a catalyst, the displacement would face a much higher barrier.

Back to sarin.  The sarin molecule closely resembles the transition state for the normal enzymatic process. Sarin looks just like hypothetical "B--A--C" transition state.  Sarin goes into the enzyme and monkey wrenches the whole process: A—B never gets a chance to react with C because sarin comes in and blocks the whole transaction. And Sarin sticks like glue to the enzyme.  Life processes end.

3 comments:

  1. I shuddered as I read this.

    But at least by comparison this makes the fiscal cliff seem like nothing to worry about.

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  2. I'm glad that I'm not in Syria.

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  3. Sarin keeps the FBI sleepless many nights. That was their bigger fear right after 9/11, much bigger than anthrax. We all remember the subway in Japan.

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