In several metabolic pathways, Nature (live systems) chooses to make esterification using thioesters (CoA) and not esters. I would like to know what is the main aim of the Nature with this choice: faster reactions or more extensive reactions?


1 Answer 1


what is the main aim of the Nature with this choice: faster reactions or more extensive reactions?

Nature is frugal, its main aim is to spend as little energy as possible in a chemical reaction. Nature will always evolve so as to use the lowest energy pathway.

If we compare the resonance structures for an ester and a thioester we see that we can draw the same three resonance structures to describe each structure.

enter image description here

However, the resonance structure on the right, the one with the double bond between the carbonyl carbon and the ester oxygen or the thioester sulfur, is less important in the sulfur case. Why? Because a double bond between second and third row atoms is not nearly as strong as a double bond between two second row elements (much better electronic overlap results between atoms of similar size).

As a result the thioester carbonyl is not as stabilized by resonance as the ester carbonyl. Said differently, the thioester carbonyl is more reactive (lower activation energy to react) than the ester carbonyl. The thioester motif provides nature with a more reactive carbonyl. This way nature doesn't have to spend as much energy to bring about reaction at this more reactive carbonyl.

  • 1
    $\begingroup$ Also worth mentioning that hydrogens that are beta to thioester carbonyls are more acidic than beta hydrogens in oxo-esters. This fact is very important for fatty acid biosynthesis and polyketide biosynthesis. $\endgroup$
    – Curt F.
    Jun 22, 2015 at 15:07
  • $\begingroup$ The reason for that is the electron contribution from the alkoxy group which is bigger than that of the thiolate, due to different sizes of the atoms, right? $\endgroup$ Jun 12, 2018 at 15:48

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service and acknowledge that you have read and understand our privacy policy and code of conduct.

Not the answer you're looking for? Browse other questions tagged or ask your own question.