Oxidation of Pyruvate and the Citric Acid Cycle

Breakdown of Pyruvate

In order for pyruvate, the product of glycolysis, to enter the next pathway, it must undergo several changes. The conversion is a three-step process (Figure).

Step 1. A carboxyl group is removed from pyruvate, releasing a molecule of carbon dioxide into the surrounding medium. This reaction creates a two-carbon hydroxyethyl group bound to the enzyme (pyruvate dehydrogenase). We should note that this is the first of the six carbons from the original glucose molecule to be removed. (This step proceeds twice because there are two pyruvate molecules produced at the end of glycolsis for every molecule of glucose metabolized anaerobically; thus, two of the six carbons will have been removed at the end of both steps.)

Step 2. The hydroxyethyl group is oxidized to an acetyl group, and the electrons are picked up by NAD+, forming NADH. The high-energy electrons from NADH will be used later to generate ATP.

Step 3. The enzyme-bound acetyl group is transferred to CoA, producing a molecule of acetyl CoA.

This illustration shows the three-step conversion of pyruvate into acetyl CoA. In step one, a carboxyl group is removed from pyruvate, releasing carbon dioxide. In step two, a redox reaction forms acetate and NADH. In step three, the acetate is transferred coenzyme A, forming acetyl CoA.
Upon entering the mitochondrial matrix, a multienzyme complex converts pyruvate into acetyl CoA. In the process, carbon dioxide is released, and one molecule of NADH is formed.

Note that during the second stage of glucose metabolism, whenever a carbon atom is removed, it is bound to two oxygen atoms, producing carbon dioxide, one of the major end products of cellular respiration.