Pyruvate Oxidation

You are in the middle of a weekend-long basketball tournament and getting ready for your next game in an hour. You start to feel tired from running all day, and your muscles are sore. Luckily, with your extensive knowledge of cellular respiration, you know how to gain some energy back!

You know you need to eat something with sugar to break down into glucose, which then becomes ATP, or how you will get your energy. Suddenly, you remembered the entire glycolysis stage of glycolysis but blanked on the second stage. So, what happens after glycolysis?

Let's dive into the process of pyruvate oxidation!

Catabolism of Glucose in Glycolysis and Pyruvate oxidation

As you probably guessed, pyruvate oxidation is what happens following glycolysis. We know glycolysis, the catabolism of glucose, produces two pyruvate molecules from which energy can be extracted. Following this and under aerobic conditions, the next stage is pyruvate oxidation.

Pyruvate (\(C_3H_3O_3\)) is an organic molecule made of a three-carbon backbone, a carboxylate(\(RCOO^-\)), and a ketone group (\(R_2C=O\)).

The energy from pyruvate is also extracted during this critical stage in connecting glycolysis to the rest of the steps in cellular respiration, but no ATP is directly made.

On top of being involved in glycolysis, pyruvate is also involved in gluconeogenesis. Gluconeogenesis is an anabolic pathway that consists of the formation of glucose from non-carbohydrates. This occurs when our body doesn't have enough glucose or carbohydrates.

Figure 1: Type of pathways shown. Daniela Lin, Study Smarter Originals.

Figure 1 compares the difference between catabolic pathways that break down molecules such as glycolysis and anabolic pathways that build up molecules such as gluconeogenesis.

Cellular Respiration Pyruvate Oxidation

After going over how the breakdown or catabolism of glucose relates to pyruvate oxidation, we can now go over how pyruvate oxidation relates to cellular respiration.

Pyruvate oxidation is one step in the cellular respiration process, albeit a significant one.

Cellular respiration is a catabolic process that organisms use to break down glucose for energy.

The overall reaction for cellular respiration is:

\(C_6H_{12}O_6 + 6O_2 \longrightarrow 6CO_2+ 6H_2O + \text {chemical energy}\)

The steps to cellular respiration are, and the process is illustrated in Figure 2:

1. Glycolysis

• Glycolysis is the process of breaking down glucose, making it a catabolic process.

• It begins with glucose and ends up broken down into pyruvate.

• Glycolysis uses glucose, a 6-carbon molecule, and breaks it down to 2 pyruvates, a 3-carbon molecule.

2. Pyruvate oxidation

• The conversion or oxidation of pyruvate from glycolysis to Acetyl COA, an essential cofactor.

• This process is catabolic since it involves oxidizing pyruvate into Acetyl COA.

• This is the process we are going to focus on today primarily.

3. Citric acid cycle (TCA or Kreb's Cycle)

• Starts with the product from pyruvate oxidation and reduces it to NADH (nicotinamide adenine dinucleotide).

• This process is amphibolic or both anabolic and catabolic.

• The catabolic part occurs when Acetyl COA is oxidized into carbon dioxide.

• The anabolic part occurs when NADH and \(\text {FADH}_2\) are synthesized.

• The Kreb's cycle uses 2 Acetyl COA and produces a total of 4 \(CO_2\), 6 NADH, 2 \(\text {FADH}_2\), and 2 ATP.

4. Oxidative phosphorylation (Electron Transport Chain)

• Oxidative phosphorylation involves the breakdown of electron carriers NADH and \(\text {FADH}_2\) to make ATP.

• The breakdown of the electron carriers makes it a catabolic process.

• Oxidative phosphorylation produces around 34 ATP. We say around because the number of ATP produced can differ as the complexes in the electron transport chain can pump different amounts of ions through.

• Phosphorylation involves adding a phosphate group to a molecule such as sugar. In the case of oxidative phosphorylation, ATP is phosphorylated from ADP.

• ATP is adenosine triphosphate or an organic compound that consists of three phosphate groups that allow cells to harness energy. In contrast, ADP is adenosine diphosphate which can be phosphorylated to become ATP.

Figure 2: Cellular Respiration overview. Daniela Lin, Study Smarter Originals.

_{Pyruvate Oxidation Location}

Now that we understand the general process of cellular respiration, we should move on to understanding where pyruvate oxidation occurs.

After glycolysis finishes, charged pyruvate is transported to the mitochondria from the cytosol, the matrix of the cytoplasm, under aerobic conditions. The mitochondrion is an organelle with an inner and outer membrane. The inner membrane has two compartments; an outer compartment and an inner compartment called the matrix.

In the inner membrane, transport proteins that import pyruvate into the matrix using active transport. Thus, pyruvate oxidation occurs in the mitochondrial matrix but only in eukaryotes. In prokaryotes or bacteria, pyruvate oxidation happens in the cytosol.

Pyruvate Oxidation Diagram

The chemical equation of pyruvate oxidation is as follows:

$$\begin{gathered} {\mathrm{C}}_3{\mathrm{H}}_3{{\mathrm{O}}_3}^{-}+{\mathrm{NAD}}^{+}+{\mathrm{C}}_{21}{\mathrm{H}}_{36}{\mathrm{N}}_7{\mathrm{O}}_{16}{\mathrm{P}}_3\mathrm{S}\to {\mathrm{C}}_{23}{\mathrm{H}}_{38}{\mathrm{N}}_7{\mathrm{O}}_{17}{\mathrm{P}}_3\mathrm{S}+\mathrm{NADH}+{\mathrm{CO}}_2+{\mathrm{H}}^{+} \\ \mathrm{Pyruvate}\mathrm{Coenzyme}\mathrm{A}\mathrm{Acetyl}\mathrm{CoA}\mathrm{Carbon}\mathrm{dioxide} \end{gathered}$$

Remember that glycolysis generates two pyruvate molecules from one glucose molecule, so each product has two molecules in this process. The equation is just simplified here.

The chemical reaction and process of pyruvate oxidation are depicted in the chemical equation shown above.

The reactants are pyruvate, NAD⁺, and coenzyme A and the pyruvate oxidation products are acetyl CoA, NADH, carbon dioxide, and a hydrogen ion. It is a highly exergonic and irreversible reaction, meaning the change in free energy is negative. As you can see, it is a relatively shorter process than glycolysis, but that does not make it any less important!

When pyruvate enters the mitochondria, the oxidation process is initiated. Overall, it is a three-step process shown in Figure 3, but we will go into more depth about each step:

1. First, pyruvate is decarboxylated or loses a carboxyl group, a functional group with carbon double bonded to oxygen and single bonded to an OH group. This causes carbon dioxide to be released into the mitochondria and results in pyruvate dehydrogenase bound to a two-carbon hydroxyethyl group. Pyruvate dehydrogenase is an enzyme that catalyzes this reaction and what initially removes the carboxyl group from pyruvate. Glucose has six carbons, so this step removes the first carbon from that original glucose molecule.

2. An acetyl group is then formed due to the hydroxyethyl group losing electrons. NAD+ picks up these high-energy electrons that were lost during the oxidation of the hydroxyethyl group to become NADH.

3. One molecule of acetyl CoA is formed when the acetyl group bound to pyruvate dehydrogenase is transferred to CoA or coenzyme A. Here, the acetyl CoA acts as a carrier molecule, carrying the acetyl group to the next step in aerobic respiration.

Figure 3: Pyruvate Oxidation illustrated. Daniela Lin, Study Smarter Originals.

Pyruvate Oxidation Products

Now, let's talk about the product of pyruvate oxidation: Acetyl CoA.

We know that pyruvate is converted to acetyl CoA through pyruvate oxidation, but what is acetyl CoA? It consists of a two-carbon acetyl group covalently linked to coenzyme A.

It has many roles, including being an intermediate in numerous reactions and playing a massive part in oxidizing fatty and amino acids. However, in our case, it is primarily used for the citric acid cycle, the next step in aerobic respiration.