Pyruvate Dehydrogenase Complex – MCAT Biochemistry | MedSchoolCoach

Pyruvate Dehydrogenase Complex

MCAT Biochemistry - Chapter 6 - Section 2.1 - Cellular Respiration - Pyruvate Dehydrogenase Complex

Sample MCAT Question - Pyruvate Dehydrogenase Complex

In eukaryotic cells, where is the pyruvate dehydrogenase complex located?

a) Cytosol

b) Endoplasmic Reticulum

c) Golgi Apparatus

d) Mitochondrial Matrix

D is correct. Mitochondrial Matrix.

The pyruvate dehydrogenase complex is a complex of enzymes that decarboxylates and oxidizes pyruvate to form acetyl-CoA and carbon dioxide. The pyruvate from glycolysis is first transported from the cytosol to the mitochondrial matrix, where the pyruvate dehydrogenase complex is located.

Pyruvate Dehydrogenase Complex Oxidizes Pyruvate Into Acetyl-CoA

Glycolysis is the start of the oxidation process of glucose that ends with the production of two molecules of pyruvate. (See this post for a discussion of the preparatory phase of glycolysis, this post for a discussion of the payoff phase, and this post for a summary of the net results of glycolysis as a whole.) Although glycolysis produces energy in the form of ATP, pyruvate is also a high-energy molecule that can be further oxidized to release more energy. The first of these processes that oxidizes pyruvate is catalyzed by the pyruvate dehydrogenase complex, an enzyme complex located in the mitochondrial matrix (Figure 1). 


Recall that glycolysis occurs in the cytosol of eukaryotic cells. Therefore, the pyruvate produced by glycolysis must first be transported into the mitochondrial matrix in order to be used by the pyruvate dehydrogenase complex. The complex then oxidizes pyruvate to form acetyl-CoA, removing a carbon dioxide (CO2) molecule in the process. You will see similar oxidative-decarboxylation reactions occurring throughout the Krebs cycle, the subsequent cellular respiration pathway. This is because one of the results of respiration is to oxidize all of the carbons from glucose into CO2


At this specific point in the respiration process, we have lost one carbon as CO2, turning a 3- carbon pyruvate molecule into a 2-carbon acetyl-CoA molecule. Also, remember that whenever something is oxidized, something else must also be reduced. In the case of the oxidation of pyruvate to acetyl-CoA, NAD+ is reduced to NADH. In this way, through the pyruvate dehydrogenase complex, more energy from pyruvate is released and captured in the form of NADH. These energy carriers (such as NADH and FADH2) are then shuttled to the electron transport chain.

Pyrvuate Decarboxylation Into Acetyl-CoA - MCAT Biochemistry
FIgure 1. Pyrvuate Decarboxylation Into Acetyl-CoA

Acteyl-CoA = Krebs Cycle Starting Reactant

Moving forward, the acetyl-CoA produced by the pyruvate dehydrogenase complex is the starting material for the Krebs cycle. The overall result of one round of the Krebs cycle is as shown below:

Acetyl-CoA + 2 NAD+ + FAD + GDP + Pi + 2 H2O → CoA-SH + 2 CO2 + 3 NADH + 3 H+ + FADH2 + GTP

The Krebs cycle also occurs in the mitochondrial matrix, and it will complete the oxidation of the acetyl group of acetyl-CoA to form two molecules of CO2. By the end of the Krebs cycle, all six carbons in the original glucose molecule have been oxidized to form six molecules of CO2.

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