Citric Acid Cycle

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Formation of Acetyl CoA from Pyruvic Acid

Introduction:

Under aerobic conditions the end product of glycolysis is pyruvic acid. The next step is the formation of acetyl coenzyme A (acetyl CoA) which is the initiator of the citric acid cycle. In carbohydrate metabolism, acetyl CoA is the link between glycolysis and the citric acid cycle.

The overall formation reaction of acetyl CoA may be represented as:

pyruvic acid + CoA + NAD+ ---> acetyl CoA + NADH + H+ + CO2

This reaction may be called the oxidative decarboxylation of pyruvic acid to acetyl CoA. The essential features are that NAD+ coenzyme is used to remove 2H's and 2e's from pyruvic acid. The reduced form, NADH, initiates the respiratory chain to regenerate NAD+. Decarboxylation which will be observed twice more in the citric acid cycle is the removal of the carboxylic acid group and subsequent conversion into CO2 .

This oxidative decarboxylation of pyruvic acid is catalyzed by the enzyme complex - pyruvate dehydrogenase. The term complex is used because three enzymes and five coenzymes are involved. The specific enzyme, pyruvate dehydrogenase contains thiamine pyrophosphate (TPP) as a coenzyme.


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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 "sandwich".

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

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Quiz: How many ATP are produced in the formation of acetyl CoA?  

Starting with glucose and going through glycolysis to the formation of acetyl CoA:

a) How many CO2 molecules are produced?
b) How many total ATP are produced?

 
How many vitamins are necessary in the formation of acetyl CoA from pyruvic acid? Name them.  

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