2/27/15

Pyruvate dehydrogenase complex

Pyruvate dehydrogenase complex is a mechanism that occurs between glycolysis and the citric acid cycle. This is because pyruvate cannot enter the citric acid cycle right after glycolysis. The purpose of pyruvate dehydrogenase complex is to modify (or convert) pyruvate, the end product of glycolysis, to the acetyl CoA, which enters the citric acid cycle.

The enzymes involved are:
  • E1: Pyruvate dehydrogenase (the TPP, or thiamine pyrophosphate is attached to it)
  • E 2: Dihydrolipoyl transacetylase (the lipoic acid is attached to it)
  • E 3: Dihydrolipoyl dehydrogenase (the FAD is attached to it)
Let's now look at what happens in details (please, look at the picture below while you read):



 E1:

First of all, pyruvate comes in and interacts with TPP, which is attached to E1 (pyruvate dehydrogenase). TPP has a ring that interacts directly with pyruvate. As a result, a CO2 is released, and the rest of the pyruvate (the hydroxyethyl group) is attached to the TPP, forming hydroxyethyl TPP.

E2:

Next, the hydroxyethyl group is transferred to the disulfide bond in the lipoic acid. Remember, the lipoic acid is attached to the second enzyme (E2) of the pyruvate dehydrogenase complex, the dihydrolipoyl transacetylase. That leads to the reduction of one of the sulfurs, because it gains hydrogen (this hydrogen comes from the hydroxyethyl group). The hydroxyethyl group without one of this hydrogens, which was given off to this sulfur is now forming acetyl group. An acetyl group attached to a sulfur forms a thioester bond, which is a high energy bond. The CoA-SH comes in and takes the acetyl group from this sulfur on the lipoic acid. CoA-SH also gives of its hydrogen to the sulfur, so now, we have made the acetyl CoA.

(Both of the sulfurs that before formed the disulfide bond are now reduced, because each of them has a hydrogen)

E3:

Furthermore, the lipoic acid cannot react with the hydroxyethyl TPP, because it doesn't have the disulfide bond. The FAD, which is attached to the third enzyme, dihydrolipoyl dehydrogenase, picks up these hydrogens, regegenerating the disulfide bond. As a result, FADH2 is formed. However, it cannot flow right to the ETC (electron transport chain), because it is attached to the dihydrolipoyl dehydrogenase. The NAD+ then comes in and becomes reduced to NADH + H+.

In addition:

The TPP is regenerated when hydroxyethyl group is removed from hydroxyethyl TPP.
The lipoic acid is regenerated when the disulfide bond is regenerated.
The FAD is regenerated when NAD+ comes in and picks up the hydrogen (a hydrogen ion is also released as a result of that) from FADH2.

This is going to be much easier to understand if you watch my video about this :).




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