Krebs Cycle question

[thewax]

Note: This is not a homework question. This is part of a study effort for a big upcoming test.

Question: What is the function/purpose of coenzyme A in cellular respiration (specifically, in the transition between glycolysis and Krebs cycle - I mean, I know that coenzyme A attaches to the acetate before the Krebs cycle and then falls off - with an extra hydrogen atom - and goes out of Krebs cycle, seemingly (and I put seemingly because I know that it has to do something) doing nothing. My question is: What does the coenzyme A do?????)

Progress I made on this question: When I first looked at Krebs cycle, I got really confused because in the post-glycolysis yet pre-Krebs cycle reaction, my textbook said in the last reaction before Krebs cycle, coenzyme A binds to the acetate. However, in the first step of Krebs cycle, CoA falls off and goes away. And my textbook did not say what it did. So I consulted my other books, hoping that they would provide me with some answers. They didn't. I went online, still believing that I could find the answer. I was still clueless - many of them said that coenzyme A plays and important role in cellular respiration but failed to expound on that idea. So I turned to here.

[lara]

The "high energy" thioester linkage makes it an excellent donor of the acetate moiety.
ACTIVATION OF ACETATE??

[whizzbee]

Here is what I think: the CoA attaches to the acetate and produces acetyl CoA; it isn't stable and makes it very reactive that it binds with the oxaloacetate in the Krebs cycle. CoA-SH then falls off and is free to bind with another acetate in order to bind them with the oxaloacetate in the Krebs cycle. it's like kinda transporter...and it activates the acetate in the first reaction of the Krebs cycle.

[thewax]

So I see - it activates the acetate so the acetate CAN bind to the oxaloacetate. Without it, the acetate would not be activated and would not be able to bind to oxaloacetate, right?????

[blcr11]

There's a lot going on with the conversion of pyruvate to acetyl-CoA to citrate reactions. That there is no net change in CoA just reflects the fact that it's part of the catalyst and catalysts by definition are regenerated and left unchanged by the process they catalyze. Here is a description of the pyruvate dehydrogenase complex reactions to form acetyl-CoA. http://rpi.edu/dept/bcbp/molbiochem/MBW ... /krebs.htm Especially watch the animation of the process and be impressed with the number of steps.

The rate-limiting step for citrate synthase (the mixed condensation reaction between acetyl-CoA and oxaloacetate to form citrate) is the enolization of the acetyl group which then acts as a nucleophile toward bound oxaloacetate. Water--freely available from the environment--preferentially hydrolyzes the resulting thioester (citryl-CoA) so the net reaction is the transfer of an acetate group to oxaloacetate removing the CoA in the process. The thiol activates in two senses: it enhances the rate of enolization (the methyl protons of the thioester are more acidic than a simple ester); and preferentially hydrolyzes away the thiol as the better leaving group in the final step of the reaction.