Wednesday, April 18, 2007

Pyruvate Dehydrogenase Reaction

Pyruvate dehydrogenase catalyzes the conversion of pyruvate to acetyl-Coenzyme A (acetyl-CoA). The reaction is coupled to the reduction of NAD+ to NADH. The reaction is an example of an oxidative decarboxylation since the other product is carbon dioxide (CO2). [Pyruvate] [Fritz Lipmann and Coenzyme A]

Acetyl-CoA is subsequently used up in the citric acid cycle and in fatty acid synthesis.

This is a very complicated reaction. It turns out that the enzyme pyruvate dehydrogenase is actually a complex of several different activities. From now on I'll refer to it as the pyruvate dehydrogenase complex (PDC).

The first step in the reaction is the decarboxylation step and it requires a special cofactor called thiamine pyrophosphate (TPP). This is vitamin B1 and it explains why that vitamin is essential. Carbon dioxide is released in this step and the remaining 2-carbon fragment of pyruvate is attached to TPP. This part of the reaction is catalyzed by a part of PDC composed of E1 subunits.

In the next step, the 2-carbon fragment is transferred to a "swinging arm" composed of a lipid arm (blue zigzag) and a head containing two sulfur (S) atoms. The swinging arm actually swings to carry the red acetyl group from one active site in the complex to another. The second site is where the acetyl group is attached to CoA. This part of the reaction is carried out by the E2 subunits in the complex.

The swinging arm carries excess electrons from the previous reaction in the form of two -SH groups. The next site visited by the swinging arm is the site where electrons are passed to another cofactor called FAD. This is the dihydrolipoamide dehydrogenase activity and it's the E3 subunits that do the job. Electrons are then passed from FADH2 to NAD+ to produce NADH2.

The complete reaction is a classic example of an electron transport chain involving three groups: the lipoamide head of the swinging arm, FAD, and NAD+. In the next article we'll look at the structure of the pyruvate dehydrogenase complex. It's one of the largest multienzyme complexes found in living cells.

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