Acetyl CoA Synthesis:
See the graphic on the left. The first step (1) in the reaction
sequence is that pyruvic acid becomes attached to a positively
charged nitrogen in the five membered ring of TPP. This is unstable
and the carboxyl group is lost as CO2 in a Decarboxylation
reaction. The acetyl group is now attached to the TPP (2).
The second reaction involves lipoic acid attached to dihydrolipoyl
transacetylase (enzyme) through an amide linkage with lysine
in the protein chain of the enzyme. The significant grouping
is the five member ring containing two sulfur.
This second reaction (3) is oxidation - reduction (the disulfide
bond is reduced) and the acetyl group is transferred from TPP
to the sulfur on lipoic acid (a thioester is formed).
The third reaction is also catalyzed by the same enzyme as
above. The acetyl group is transferred onto coenzyme A (4).
The final two reactions catalyzed by the third enzyme, dihydrolipoyl
dehydrogenase, involve the regeneration of the disulfide bond
in the five member ring in lipoamide (5). FAD cause the oxidation
and formation of the disulfide bond to form the ring.
Finally FADH2 reacts with NAD+ in the
electron transport chain (6) .The NADH + H+ formed
in the last reaction initiates the electron transport chain sequence.
The figure is a good approximation of how the reaction works
because the enzyme complex is actually arranged in a spherical
Link to Shock
Wave Animation - pyruvic acid to acetyl CoA by Joyce J. Diwan,
Rensselaer Polytechnic Institute
Link to Animation
steps and shows structures - Brooks-Cole
Coenzymes - Chime
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