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.


  1. I shuddered as I read this.

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

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

  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.