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

Dear Miss Metabolism...

(Mouse over the purple text for explanations.)

Dear Miss Metabolism,

I don't know what to do with myself, I'm so lonely. I used to be carbon atoms 4, 5 and 6 of a happy fructose-1,6-bisphosphate compound, but I guess I forgot how lucky I was, got restless, and decided I wanted us to split up.

I had seen so many of my friends going off into glycolysis and it looked like fun, and I was curious. I had no idea what a big mistake I was making, but I told my other half I wanted a trial separation, and here I am.

We found an aldolase enzyme, it wasn't hard, there was practically one on every street corner, and she promised us that it would just be a reversible reaction, that we could get back together whenever we wanted. Technically, I guess she was telling the truth. Except that after I became a dihydroxyacetone phosphate, I never saw my glyceraldehyde 3-phosphate again.

I guess I thought she would wait for me to get it out of my system, but she didn't. She rushed off into glycolysis, maybe she was feeling hurt, and left me all alone. Glyceraldehyde-3-P dehyrogenase enzymes won't even look at me, so I'm just stuck here.


Please Miss Metabolism, I'm just a foolish intermediate who didn't know how good I had it, please tell me what I should do now?


Yours,
Sad in the Cytosol



Dear Sad in the Cytosol,

Don't be too hard on yourself, you weren't to know this, but those aldolase enzymes are a bunch of home-wreckers! They always say the separation is temporary, that you can both reconcile later if you find you're unhappy, but most of the time, the two compounds just get completely broken down in to carbon dioxide and float away. It's hard being single.

Listen, chances are, your darling GAP is long-gone. All you can do now is remember the good times, and get on with your metabolism. Basically, you have three main options:

1. Mind the GAP. Finding another glyceraldehyde-3-P to settle down with might be difficult, but if you are in a cell that's doing gluconeogenesis, it's not such a long shot.



2. Get fat. Why not try an alternative metabolic lifestyle, and get reduced to a glycerol-3-P. You could settle down with some nice fatty acids (not hard on today's modern 'diets'), and live the quiet life of a triacylglycerol molecule, or the fast-paced career of a phospholipid.



3. Switch teams. If life alone really is that unbearable, why not find a triose phosphate isomerase and become a GAP yourself. Maybe by following your ex's footsteps, you might even get some closure. Be careful though, if you go all the way to becoming an acetyl CoA, you will have given up on life as a carbohydrate forever.

So think carefully before you make your decision, even reversible reactions can have irreversible consequences.

Dynamically yours,
Miss Metabolism