Thursday, 20 June 2013

Zombie Metabolism: Electron transport chain and oxidative phosphorylation

I think I'm on to something guys, I think I've found a way to poison zombies... but first some background.

Everybody knows, that the best bit of metabolism is the electron transport chain (because that is normally the last lecture! I'm kidding, of course). But just in case you can't remember what that is, here is a reminder.

The electron transport chain is the culmination of aerobic metabolism, the final extraction point for energy from anything sugary, fatty or... proteiny isn't a word... meaty.

Basically, all the catabolism that went before, kept producing reduced coenzymes. NADH here, FADH2 there, and what was the point of it?

The point, my friends, was the electron transport chain.
(please ignore the extra bits of text - do you think it's easy blogging about zombie metabolism during the zombiepocalypse?)

The electron transport chain takes all the reduced goodness of the coenzymes, and uses it to remove protons from the matrix of the mitochondria. These protons desperately want to get back in, and the main way to do that, is via ATP synthase, which uses their desperation (it's not nice to discuss proton-motive force in polite company) to make ATP.

So how do we use this information to poison zombies?

If you remember, I said that zombies are respiring verrrrrryyyyyyy slooooowwwwlllllyyy.

The outcome of this highly pertinent factoid is that zombies look like they don't breathe or need oxygen, but they do. It's just that they can survive being deprived of it for a ridiculously long period of time. Getting buried by a loved one until they can claw their way out of the ground, for example, is no problem at all. As many of us know from personal experience.


So what's their poison?

Dinitrophenol (or any other similar uncoupler).

Seriously? I hear you ask yourself, the herbicide? What the...?

I'll explain.

Dinitrophenol is a lipid-soluble weak acid. This means that it can bind or release protons fairly easily, depending on the pH, and that it can dissolve across lipid membranes easily. The result of this, in your average human, is that it can allow those protons another way into the mitochondria. This means that the protons are no longer so desperate to get in via ATP synthase, and a lot of energy is wasted.

Another side effect is that oxygen usage increases, because as protons re-enter the mitochondrial matrix, its easier for the electron transport chain to pump them back out again, using up oxygen in the process.

So then, why would this act as a poison to zombies? Well, it removes one of their major advantages over us. Your average zombie only gets to eat about once a week, but they can survive for much longer than that without eating, while we, on the other hand, like to eat at least once a day (wishful thinking...). This means that they can outlive (or outdead...?) us just by waiting long enough. Also, they don't need to breathe very often, which means they are harder to kill.

But if we could speed up their metabolism, they would probably starve, or at least get weaker. Also, the need to breathe... no more of those pesky underwater zombie attacks that make swimming so much more eventful than it used to be.

With all those open wounds, I could probably just drop it on them from tall buildings, but where will I get bucket loads of DNP...?

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