Question

AcetylCoA is considered a high energy molecule because hydrolysis of the thioester bond is very exergonic (∆G is - ). In contrast, the analogous oxyester would not be nearly as exergonic. Why is that? Provide one free energy diagram to show hydrolysis of both a thioester and an oxyester. Also provide an explanation for the difference in stability between thioesters and oxyesters. Your explanation should include relevant electron configurations and orbital overlap considerations

Answer 1

• Acetyl coenzyme A or acetyl-CoA is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism.
• Its main function is to deliver to acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for energy production.
• Coenzyme A (CoASH or CoA) consists of a β-mercaptoethylamine group linked to the vitamin pantothenic acid through an amide linkage and 3'-phosphorylated ADP. This thioester linkage is a high energy bond, which is particularly reactive. Hydrolysis of the thioester bond is exergonic (−31.5 kJ/mol).
• 
• comparing the resonance structures for an oxyester and a thioester we see by the samethree resonance structures to describe each structure.

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. Because a double bond between second and third row atoms is not nearly as strong as a double bond between two second row elements having 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, 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. In this way it doesn't have to spend as much energy to bring about reaction at this more reactive carbonyl.

The thioester linkage to acetyl coA is a high energy bond, which is particularly reactive, which is having less stabilization comparing oxyester. Hydrolysis of the thioester bond is exergonic (−31.5 kJ/mol).

The provided answer may be correct and definitely useful.