10.1 Glycolysis and pyruvate oxidation

2 min readjuly 22, 2024

is the first step in cellular respiration, breaking down glucose into . This process occurs in the and doesn't require oxygen, making it crucial for energy production in various conditions.

Pyruvate's fate depends on oxygen availability. In aerobic conditions, it enters the . In anaerobic conditions, it undergoes . Understanding these pathways is key to grasping cellular energy production.

Glycolysis and Pyruvate Oxidation

Steps and enzymes of glycolysis

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  • Glycolysis breaks down glucose into pyruvate through a 10-step process (cytosol, anaerobic)
  • Key steps and enzymes:
    1. Hexokinase phosphorylates glucose to glucose-6-phosphate (G6P)
    2. Phosphoglucose isomerase converts G6P to fructose-6-phosphate (F6P)
    3. phosphorylates F6P to fructose-1,6-bisphosphate (F1,6BP) (irreversible, rate-limiting)
    4. cleaves F1,6BP into glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP)
    5. converts DHAP to G3P
    6. oxidizes G3P to 1,3-bisphosphoglycerate (1,3BPG), reduces to
    7. converts 1,3BPG to 3-phosphoglycerate (3PG), produces ()
    8. converts 3PG to 2-phosphoglycerate (2PG)
    9. dehydrates 2PG to phosphoenolpyruvate (PEP)
    10. converts PEP to pyruvate, produces ATP (substrate-level phosphorylation)

Glucose to pyruvate conversion

  • Glycolysis converts one glucose molecule into two pyruvate molecules
  • Energy yield per glucose molecule:
    • Net production of 2 ATP via substrate-level phosphorylation (4 ATP produced, 2 ATP consumed)
    • Net production of 2 NADH (used in electron transport chain for ATP generation)
  • Redox reactions involve NAD+ reduction to NADH by glyceraldehyde-3-phosphate dehydrogenase
  • Phosphorylation events occur twice through substrate-level phosphorylation (phosphoglycerate kinase and pyruvate kinase steps)

Pyruvate fate in aerobic vs anaerobic conditions

  • Aerobic conditions (oxygen available):
    • Pyruvate converted to by , enters citric acid cycle
    • NADH from glycolysis used in electron transport chain for ATP generation
  • Anaerobic conditions (oxygen unavailable):
    • Fermentation regenerates NAD+ for glycolysis continuation
    • Lactic acid fermentation (animals, some microorganisms): pyruvate reduced to lactate by , NADH oxidized to NAD+
    • Alcoholic fermentation (yeast, some microorganisms): pyruvate decarboxylated to acetaldehyde by , acetaldehyde reduced to ethanol by , NADH oxidized to NAD+

Pyruvate dehydrogenase complex role

  • Pyruvate dehydrogenase complex (PDC) is a multi-enzyme complex in the
  • Catalyzes irreversible of pyruvate to acetyl-CoA, committing pyruvate to citric acid cycle
  • Reaction: Pyruvate+CoA+NAD+AcetylCoA+CO2+NADHPyruvate + CoA + NAD^+ \rightarrow Acetyl-CoA + CO_2 + NADH
  • PDC regulation:
    • Allosteric inhibition by high acetyl-CoA and NADH levels
    • Covalent modification (phosphorylation) by pyruvate dehydrogenase kinase inactivates PDC
    • Dephosphorylation by pyruvate dehydrogenase phosphatase activates PDC
  • Acetyl-CoA produced by PDC enters citric acid cycle, generating NADH and for electron transport chain and ATP production through oxidative phosphorylation

Key Terms to Review (28)

Acetyl-CoA: Acetyl-CoA is a central metabolite in cellular metabolism, serving as a key substrate for energy production and biosynthesis. It is formed from the breakdown of carbohydrates, fats, and proteins, linking glycolysis and the citric acid cycle, and plays a critical role in converting energy from food into usable forms for the cell.
Alcohol dehydrogenase: Alcohol dehydrogenase is an enzyme that catalyzes the conversion of ethanol to acetaldehyde in the liver, playing a crucial role in alcohol metabolism. This enzyme is essential for breaking down alcohol consumed in beverages, allowing the body to process and eliminate it effectively. It helps maintain the balance of energy production and detoxification in cells, connecting to broader metabolic pathways like glycolysis and pyruvate oxidation.
Aldolase: Aldolase is an enzyme that catalyzes the reversible reaction in which fructose-1,6-bisphosphate is split into two three-carbon molecules during glycolysis. This enzyme plays a crucial role in the breakdown of glucose for energy, linking it directly to both glycolysis and fermentation processes, as it aids in converting sugars into usable energy forms like ATP.
Allosteric regulation: Allosteric regulation is a mechanism by which the function of an enzyme is modulated by the binding of an effector molecule at a site other than the active site. This type of regulation allows enzymes to respond to changes in cellular conditions, fine-tuning metabolic pathways and ensuring efficient energy production and resource allocation.
ATP: Adenosine triphosphate (ATP) is a nucleotide that serves as the primary energy currency of the cell, enabling various biochemical reactions. It is essential for energy transfer within cells, acting as a mediator for energy storage and utilization during metabolic processes. ATP plays a vital role in cellular respiration, photosynthesis, and other energy-related pathways, making it a central molecule in both plant and animal life.
Carbon dioxide release: Carbon dioxide release refers to the process by which carbon dioxide (CO2) is produced and expelled as a byproduct of cellular respiration. This process occurs in the latter stages of metabolism, particularly during the conversion of pyruvate into acetyl-CoA and during the Krebs cycle, where energy from glucose is harnessed for cellular functions while simultaneously generating CO2.
Citric acid cycle: The citric acid cycle, also known as the Krebs cycle or TCA cycle, is a series of chemical reactions used by all aerobic organisms to generate energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. It plays a crucial role in cellular respiration, linking the breakdown of glucose in glycolysis and pyruvate oxidation to the production of ATP through oxidative phosphorylation in the electron transport chain.
Cytosol: Cytosol is the aqueous component of the cytoplasm in a cell, where various metabolic processes occur. It serves as a medium for the suspension of organelles and other cell structures, facilitating cellular functions such as glycolysis and pyruvate oxidation. This gel-like substance is rich in enzymes and substrates necessary for metabolic pathways, making it essential for energy production.
Enolase: Enolase is an important enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate in the glycolytic pathway, playing a crucial role in cellular energy production. This enzyme helps facilitate the removal of water from 2-phosphoglycerate, forming a high-energy compound that is essential for subsequent ATP generation during glycolysis. Additionally, enolase has implications in fermentation processes, as it contributes to anaerobic metabolism when oxygen levels are low.
FADH2: FADH2 is a reduced form of flavin adenine dinucleotide, an important electron carrier in cellular respiration. It plays a crucial role in energy production by transporting electrons to the electron transport chain, contributing to the generation of ATP during oxidative phosphorylation.
Feedback Inhibition: Feedback inhibition is a regulatory mechanism in cellular processes where the end product of a metabolic pathway inhibits an enzyme involved in its own synthesis. This process helps maintain homeostasis by preventing the overproduction of substances, allowing cells to efficiently manage their resources and respond to changes in their environment.
Fermentation: Fermentation is a metabolic process that converts sugar to acids, gases, or alcohol in the absence of oxygen. It allows cells to produce energy when oxygen is scarce and plays a crucial role in various organisms, including yeast and some bacteria, as it enables them to generate ATP through substrate-level phosphorylation.
Glyceraldehyde-3-phosphate dehydrogenase: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an essential enzyme in the glycolytic pathway that catalyzes the conversion of glyceraldehyde-3-phosphate into 1,3-bisphosphoglycerate while reducing NAD+ to NADH. This reaction is critical for energy production as it helps in the generation of ATP through subsequent steps in glycolysis and connects to cellular respiration processes.
Glycolysis: Glycolysis is the metabolic pathway that breaks down glucose into pyruvate, yielding energy in the form of ATP. This process occurs in the cytoplasm of the cell and is the first step in both aerobic and anaerobic respiration, linking the breakdown of glucose to the production of energy, which is essential for cellular functions.
Lactate dehydrogenase: Lactate dehydrogenase is an enzyme that catalyzes the conversion of pyruvate to lactate while oxidizing NADH to NAD\^+. This reaction plays a crucial role in anaerobic metabolism, particularly during glycolysis and pyruvate oxidation, allowing cells to regenerate NAD\^+ needed for continued ATP production. Furthermore, lactate dehydrogenase is important in various alternative metabolic pathways and serves as a marker for metabolic regulation under different physiological conditions.
Mitochondrial matrix: The mitochondrial matrix is the innermost compartment of a mitochondrion, surrounded by the inner mitochondrial membrane. It plays a critical role in cellular respiration and energy production, housing key enzymes, mitochondrial DNA, and ribosomes necessary for various metabolic processes. This environment is essential for the citric acid cycle and oxidative phosphorylation, where energy-rich molecules are produced from the breakdown of carbohydrates and fats.
NAD+: NAD+ (Nicotinamide adenine dinucleotide) is a coenzyme found in all living cells that plays a critical role in redox reactions, carrying electrons from one reaction to another. It acts as an electron acceptor in metabolic processes, facilitating the transfer of energy through its conversion to NADH, which is crucial for cellular respiration and energy production.
NADH: NADH, or nicotinamide adenine dinucleotide (in its reduced form), is a crucial coenzyme that plays a significant role in cellular respiration and metabolism. It serves as an electron carrier, transporting electrons from one reaction to another, particularly in processes like glycolysis, the citric acid cycle, and oxidative phosphorylation. By accepting and donating electrons, NADH is key in generating ATP, the energy currency of the cell.
Oxidative Decarboxylation: Oxidative decarboxylation is a biochemical process that involves the removal of a carboxyl group from a molecule as carbon dioxide, coupled with the oxidation of the remaining molecule, leading to the production of reduced cofactors like NADH or FADH2. This process plays a crucial role in cellular respiration, particularly in converting pyruvate into acetyl-CoA after glycolysis, facilitating the entry into the citric acid cycle.
Phosphofructokinase: Phosphofructokinase (PFK) is a key regulatory enzyme in the glycolytic pathway that catalyzes the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate, using ATP as a phosphate donor. This reaction is crucial because it serves as one of the primary control points for glycolysis, allowing the cell to regulate energy production according to its needs. As a pivotal enzyme, PFK plays a significant role in linking glycolysis and subsequent metabolic pathways like pyruvate oxidation and fermentation.
Phosphoglycerate kinase: Phosphoglycerate kinase is an enzyme that catalyzes the conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate in the glycolytic pathway, along with the concurrent transfer of a phosphate group to ADP, forming ATP. This step is crucial for energy production during glycolysis, as it represents one of the substrate-level phosphorylation reactions that directly generates ATP. Additionally, this enzyme plays a significant role in regulating the flow of metabolites through glycolysis and connecting carbohydrate metabolism to energy yield.
Phosphoglycerate mutase: Phosphoglycerate mutase is an enzyme that catalyzes the conversion of 3-phosphoglycerate to 2-phosphoglycerate in the glycolytic pathway. This reaction is crucial for the rearrangement of carbon molecules, allowing for subsequent steps in glucose metabolism. The enzyme plays a vital role in facilitating the proper flow of metabolites during glycolysis and contributes to the overall energy production within cells.
Pyruvate: Pyruvate is a key intermediate in cellular metabolism that forms from the breakdown of glucose during glycolysis. It acts as a crucial junction point, linking anaerobic and aerobic respiration processes, where it can be converted into acetyl-CoA for the citric acid cycle or fermented to produce energy in low-oxygen environments. Understanding pyruvate is essential for grasping how cells extract energy from nutrients and regulate metabolic pathways.
Pyruvate decarboxylase: Pyruvate decarboxylase is an enzyme that catalyzes the conversion of pyruvate into acetaldehyde and carbon dioxide in the process of alcoholic fermentation. This reaction is crucial for cells that undergo anaerobic respiration, allowing them to regenerate NAD+ from NADH and continue glycolysis in the absence of oxygen.
Pyruvate dehydrogenase complex: The pyruvate dehydrogenase complex is a multi-enzyme complex that catalyzes the conversion of pyruvate into acetyl-CoA, a crucial step in cellular respiration. This complex links glycolysis to the citric acid cycle by facilitating the decarboxylation of pyruvate and the reduction of NAD+ to NADH. Its activity is vital for energy production and it plays a key role in determining metabolic pathways based on the cell's energy needs.
Pyruvate kinase: Pyruvate kinase is an essential enzyme that catalyzes the final step of glycolysis, converting phosphoenolpyruvate (PEP) to pyruvate while producing ATP from ADP. This enzyme plays a crucial role in energy metabolism, linking glycolysis to cellular respiration and fermentation processes, thus influencing overall energy production in cells.
Substrate-level phosphorylation: Substrate-level phosphorylation is a metabolic process in which a phosphate group is directly transferred from a substrate molecule to ADP, forming ATP without the involvement of an electron transport chain. This process occurs in several key pathways of cellular respiration, where energy-rich molecules are broken down, leading to the generation of ATP through direct enzymatic action.
Triose phosphate isomerase: Triose phosphate isomerase is an enzyme that catalyzes the interconversion between dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P), which are both three-carbon sugar phosphates. This reaction is crucial in metabolic pathways such as glycolysis and gluconeogenesis, enabling cells to efficiently utilize glucose for energy production. The enzyme facilitates a key step in these pathways, highlighting its importance in cellular respiration and energy metabolism.
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