Why can't pyruvate be used directly in the Krebs cycle? Why does it have to be converted to acetyl before it enters the cycle?

Excluding the reason that the shape of pyruvate is different than acetyl and therefore it would not fit the enzymes involved in the Krebs cycle, what is the advantage of converting pyruvate to acetyl?

  • $\begingroup$ "Excluding the reason that the shape of pyruvate ... would not fit the enzymes involved in the Krebs cycle" -- that's a pretty big exclusion. Obviously pyruvate cannot be used directly because it doesn't fit. It rather sounds like you're asking why the cycle isn't made up of completely different enzymes? But metabolism is evolved, and there is no special reason why it looks the way it does, except that this solution was found by evolution. I'm not sure the question is answerable. (But maybe I don't understand it correctly.) $\endgroup$
    – Roland
    Oct 10 '17 at 6:23
  1. Oxidative decarboxylation of pyruvate to acetyl-CoA by pyruvate dehydrogenase is coupled with reduction of NAD+, which can feed into the electron transport chain.
  2. CoASH activates the acetate: hydrolysis of the thioester is thermodynamically favourable and drives the reaction catalyzed by citrate synthase.
  3. Conversion of pyruvate to acetyl-CoA commits it to a subset of possible fates (including the tricarboxylic acid cycle) and is therefore a key regulatory step.

You can read more about this in most introductory biochemistry texts, like this one.

Also note that pyruvate actually can enter the TCA cycle via carboxylation by pyruvate carboxylase to oxaloacetate. This reaction requires energy in the form of ATP and is used to regenerate TCA cycle intermediates as they are siphoned off for anabolic pathways.


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