I am thinking Citric Acid cycle and activation of the end parts of Acetyl and alfa-ketoglutarate. Let's consider only now Acetyl to make things simpler.

I have tried to explain the thing by symmetry - phosphate tetrahedral, while coenzyme A seems to be mostly some V shaped. However, it does not help.

Can human body use Acetyl Phosphate instead of Acetyl CoA in TCA in some situations?

I know that you can activate acetyl-CoA again by phosphate:

acetyl-CoA + phosphate <-> CoA + acetyl phosphate
  • $\begingroup$ Are you asking if acetyl groups can enter the TCA cycle directly from acetyl phosphate? If so, are you asking if citrate synthase can use acetyl phosphate as an alternative substrate or do you envisage the existence of another "citrate synthase". $\endgroup$
    – Alan Boyd
    Commented Feb 25, 2013 at 15:35
  • 1
    $\begingroup$ No, I am not asking if Acetyl group can enter TCA cycle directly. I am asking if Acetyl Phosphate can enter TCA cycle directly. So I am asking if citrate synthase can use acetyl phosphate as an alternative substrate. If no, why? $\endgroup$ Commented Feb 25, 2013 at 19:57

1 Answer 1


Enzymes are usually specific to a greater or lesser extent for their substrates. In this case we are looking at citrate synthase which catalyses a condensation reaction in which the acetyl group from acetyl-CoA is added to an oxaloacetate molecule to form citrate. This is the entry point for carbon into the TCA cycle for energy production. The condensation reaction follows an ordered pathway: oxalocatetate binds first and this results in a conformational change which increases the enzyme's affinity for acetyl-CoA by a factor of 20.

Citrate synthase is highly specific for acetyl-CoA as a substrate. The cited reference discusses several aspects of this specificity. The enzyme has a well-defined binding site for CoA, with contacts from both the small and large subunits. This includes the recognition of the adenylyl portion of the molecule.

A relevant quotation from the review:

"Citrate synthase is highly specific towards its substrates. The condensation reaction occurs only with the physiological substrates oxaloacetate and acetyl-CoA."

So, the answer is that citrate synthase cannot use acetyl-phosphate as a substrate because of its specificity for acetyl-CoA.

Wiegand,G and Remington, SJ (1986) Citrate Synthase: Structure, Control, and Mechanism. Ann. Rev. Biophys. 15: 97–117


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