Pyruvate Oxidation

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Pyruvate Oxidation Pyruvate Oxidation

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    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 oxidation is the stage where pyruvate is oxidized and converted to acetyl CoA, producing NADH and releasing one molecule of CO2.

    Oxidation occurs when either oxygen is gained, or there is a loss of electrons.

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

    Anabolic pathways require energy to buildup or construct molecules, as shown in Figure 1. For example, the buildup of carbohydrates is an example of an anabolic pathway.

    Catabolic pathways create energy through the breakdown of molecules, as shown in Figure 1. For instance, the breakdown of carbohydrates is an example of the catabolic pathway.

    Amphibolic pathways are pathways that include both anabolic and catabolic processes.

    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.

    Pyruvate Oxidation Type of Pathway Study SmarterFigure 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.

    For more detailed information regarding glycolysis, please visit our article "Glycolysis."

    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.

    NADH or nicotinamide adenine dinucleotide is a coenzyme that acts as an energy carrier as it transfers electrons from one reaction to the next.

    \(\text {FADH}_2\) or flavin adenine dinucleotide is a coenzyme that acts as an energy carrier, just like NADH. We use flavin adenine dinucleotide sometimes instead of NADH because one step of the Citric Acid Cycle doesn't have enough energy to reduce NAD+.

    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.

    Pyruvate Oxidation Cellular Respiration Study SmarterFigure 2: Cellular Respiration overview. Daniela Lin, Study Smarter Originals.

    For more in-depth information regarding cellular respiration, please visit our article "Cellular Respiration."

    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.

    To learn more about active transport, refer to our article on "Active Transport".

    Pyruvate Oxidation Diagram

    The chemical equation of pyruvate oxidation is as follows:

    C3H3O3- + NAD+ + C21H36N7O16P3S C23H38N7O17P3S + NADH + CO2 + H+Pyruvate Coenzyme A Acetyl CoA Carbon dioxide

    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.

    A coenzyme or cofactor is a compound that's not a protein that helps an enzyme function.

    Aerobic respiration uses oxygen to make energy from sugars such as glucose.

    Anaerobic respiration does not use oxygen to make energy from sugars such as glucose.

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

    Remember that one glucose molecule produces two pyruvate molecules, so each step occurs twice!

    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.

    Acetyl CoA and NADH, the products of pyruvate oxidation, both work to inhibit pyruvate dehydrogenase and therefore contribute to its regulation. Phosphorylation also plays a role in the regulation of pyruvate dehydrogenase, where a kinase makes it become inactive, but phosphatase reactivates it (both of these are regulated as well).

    Also, when enough ATP and fatty acids are oxidized, pyruvate dehydrogenase and glycolysis are inhibited.

    Pyruvate Oxidation - Key takeaways

    • Pyruvate oxidation involves oxidizing pyruvate into acetyl CoA, necessary for the next stage.
    • Pyruvate oxidation occurs within the mitochondrial matrix in eukaryotes and the cytosol in prokaryotes.
    • The chemical equation for pyruvate oxidation involves: \( C_3H_3O_3^- + C_{21}H_{36}N_7O_{16}P_{3}S \longrightarrow C_{23}H_{38}N_7O_{17}P_{3}S + NADH + CO_2 + H^+\)
    • There are three steps in pyruvate oxidation: 1. A carboxyl group is removed from pyruvate. CO2 is released. 2. NAD+ is reduced to NADH. 3. An acetyl group is transferred to coenzyme A, forming acetyl CoA.
    • The products of pyruvate oxidation are two acetyl CoA, 2 NADH, two carbon dioxide, and a hydrogen ion, and the acetyl CoA is what initiates the citric acid cycle.

    References

    1. Goldberg, D. T. (2020). AP Biology: With 2 Practice Tests (Barron’s Test Prep) (Seventh ed.). Barrons Educational Services.
    2. Lodish, H., Berk, A., Kaiser, C. A., Krieger, M., Bretscher, A., Ploegh, H., Amon, A., & Scott, M. P. (2012). Molecular Cell Biology 7th Edition. W.H. Freeman and CO.
    3. Zedalis, J., & Eggebrecht, J. (2018). Biology for AP ® Courses. Texas Education Agency.
    4. Bender D.A., & Mayes P.A. (2016). Glycolysis & the oxidation of pyruvate. Rodwell V.W., & Bender D.A., & Botham K.M., & Kennelly P.J., & Weil P(Eds.), Harper's Illustrated Biochemistry, 30e. McGraw Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=1366§ionid=73243618
    Frequently Asked Questions about Pyruvate Oxidation

    What does pyruvate oxidation start?

    Pyruvate oxidation leads to acetyl CoA being formed which is then used in the citric acid cycle, the next step in aerobic respiration. It begins once pyruvate is produced from glycolysis and transported to the mitochondria. 

    Where does pyruvate oxidation occur?

    Pyruvate oxidation occurs within the mitochondrial matrix, and pyruvate is transported to the mitochondria following glycolysis. 

    What is pyruvate oxidation?

    Pyruvate oxidation is the stage where pyruvate is oxidized and converted to acetyl CoA, which in turn produces NADH and releases one molecule of CO2.

    What does pyruvate oxidation produce?

    It produces acetyl CoA, NADH, carbon dioxide, and a hydrogen ion. 

    What happens during pyruvate oxidation? 

    1. A carboxyl group is removed from pyruvate. CO2 is released. 2. NADis reduced to NADH. 3. An acetyl group is transferred to coenzyme A forming acetyl CoA. 

    Test your knowledge with multiple choice flashcards

    What type of process is pyruvate oxidation?

    What is pyruvate?

    How many pyruvate molecules does glycolysis produce? 

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