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...?

Succs to be me...

Dear Miss Metabolism,

I am a complex II, and I am being bullied. I work just as hard as any other enzyme complex, I contribute as much as I can, but the other complexes make fun of me because I can't pump protons like they do. Even Complex V teases me, and she lets protons back in!!!

How is that fair?

I can't control the redox potential of succinate or ubiquinone, any more than they can control the redox potentials of their substrates and products.

I wouldn't mind so much, but they're making my little FAD depressed. Sometimes I hear him crying himself to sleep at night. Its not right for a little prosthetic group to hear his enzyme being humilated like this, its bad for his self-esteem.

I've tried explaining these things to the other complexes, but they just won't listen!

Any advice on how to handle this?

Yours truly,
Succs To Be Me


Dear Succs To Be Me,

The first thing I want you to do is stop talking about yourself like that! You are an important complex, and don't ever forget it!

Its true that via Complex I, the electron transport chain can continue along without you, but there is more to a half-life than transporting electrons. Its true that you don't pump protons, but there is more to a half-life than generating electrochemical gradients.

Perhaps this sounds cliche, but I am pretty sure they are just jealous. Lets not forget that the succinate dehydrogenase part of you is absolutely integral to the citric acid cycle, and what would happen if you stopped functioning? I'd like to see them get much in the way of reducing power then, the supply would become pretty scarce, I can tell you!

And in addition to all that, you might have a role in oxygen sensing and tumour suppression too!

I wouldn't be surprised if Complex I was the one instigating all this, after all, you are the competition, and he probably sees you as a threat. As for Complex III and IV, they should be ashamed of themselves, how can they make fun of you while still accepting your electrons? They would do well to remember that the real reason they can pump protons is because of the difference in the reduction potentials of their substrates and products, and not because of any intrinsic property that they have.

And my sympathies to your little FAD, although we coddle and fuss over them, don't worry, prosthetic groups are alot tougher than we give them credit for, he'll be alright, as long as you don't take their insults to heart.

Having hopefully activated your self-esteem a little bit, let me just say this. Bullies are insecure, and they crave a response from those they bully. To paraphrase a human saying, 'Enzymes need substrates'. Show them just how much you don't care, and if they really get on your nerves, take a break for a while... when the citric acid cycle grinds to a halt, they'll be begging you to start transporting electrons again.

Keep your chin up,
Miss Metabolism