Glycolysis: Cellular Energy Extraction

• Glycolysis is a series of reactions that extract energy from glucose by splitting it into two three-carbon molecules called pyruvates
• Glycolysis is an ancient metabolic pathway, meaning that it evolved very early
• The process is used by most organisms on earth
• In eukaryotes, glycolysis takes place in the cytoplasm of the cell
• Glycolysis does not require oxygen (it is anaerobic)
• Glycolysis can proceed in the presence or absence of oxygen
• Glycolysis involves 10 steps, each catalyzed by a different enzyme

Phases of Glycolysis

• Glycolysis is split into two main phases:
  • The energy-requiring phase
  • The energy-releasing phase

Energy-Requiring Phase

• In this phase, the starting molecule of glucose is rearranged, and two phosphate groups are attached to it
• The phosphate groups make glucose more unstable and allow it to be split into two three-carbon sugars
• The phosphate groups used to phosphorylate glucose come from ATP
• Two ATP molecules are used during this phase

Energy-Releasing Phase

• In this phase, each three-carbon sugar is converted into pyruvate
• ATP and NADH are produced
• Because this phase occurs twice for each molecule of glucose, four molecules of ATP and two molecules of NADH are produced

Glycolysis Input

• 1 Glucose
• 2 ATP
• 2 NAD+
• 4 ADP
• 2 Pi

Glycolysis Output

• 2 Pyruvate
• 2 ADP
• 4 ATP
• 2 NADH
• 2 H+
• 2 H2O

ATP Yield

• Glycolysis has a net production of two ATP molecules
• Four ATP molecules are produced, but two are used in the energy-requiring phase
• Glycolysis results in a net production of two NADH molecules

Steps of Glycolysis

• Step 1: Hexokinase phosphorylates glucose, forming glucose-6-phosphate.
  • Traps glucose inside the cell.
  • Uses one ATP.
• Step 2: Phosphoglucose isomerase converts glucose-6-phosphate into fructose-6-phosphate.
  • Isomerization reaction.
• Step 3: Phosphofructokinase phosphorylates fructose-6-phosphate, forming fructose-1,6-bisphosphate.
  • Uses one ATP.
  • Important regulatory step.
• Step 4: Aldolase cleaves fructose-1,6-bisphosphate into two three-carbon sugars:
  • Dihydroxyacetone phosphate (DHAP)
  • Glyceraldehyde-3-phosphate (G3P).
• Step 5: Triose phosphate isomerase converts DHAP into G3P.
  • Ensures that only G3P continues in glycolysis.
• Step 6: Glyceraldehyde-3-phosphate dehydrogenase oxidizes G3P, phosphorylating it with inorganic phosphate to form 1,3-bisphosphoglycerate.
  • Produces NADH from NAD+.
• Step 7: Phosphoglycerate kinase transfers a phosphate group from 1,3-bisphosphoglycerate to ADP, forming ATP and 3-phosphoglycerate.
  • Generates ATP.
• Step 8: Phosphoglycerate mutase converts 3-phosphoglycerate into 2-phosphoglycerate.
  • Prepares the molecule for the next step.
• Step 9: Enolase removes water from 2-phosphoglycerate, forming phosphoenolpyruvate (PEP).
  • Creates a high-energy phosphate bond.
• Step 10: Pyruvate kinase transfers a phosphate group from PEP to ADP, forming ATP and pyruvate.
  • Generates ATP.
  • Regulatory step.

Fate of Pyruvate

• After glycolysis, the pyruvate molecules are transported into the mitochondria
• Pyruvate is converted into acetyl CoA, feeding into the citric acid cycle
• If oxygen is unavailable, pyruvate undergoes fermentation
• In fermentation, pyruvate is converted into lactic acid or ethanol

Regulation of Glycolysis

• Glycolysis is regulated at several steps
• Regulation ensures ATP is produced only when needed

Key Regulatory Enzymes

• Hexokinase: Inhibited by glucose-6-phosphate
  • High levels of glucose-6-phosphate signal that the cell does not need more glucose for energy or storage
• Phosphofructokinase (PFK): Regulated by several factors
  • ATP: High levels inhibit PFK, indicating sufficient energy supply
  • AMP: High levels activate PFK, indicating a need for more energy
  • Citrate: High levels inhibit PFK, coordinating glycolysis with the citric acid cycle
• Pyruvate Kinase: Inhibited by ATP and alanine
  • ATP: Signals sufficient energy supply
  • Alanine: Indicates an abundance of building blocks
  • Activated by fructose-1,6-bisphosphate, the product of the PFK reaction, providing feedforward activation

Importance of Glycolysis

• Glycolysis is a central metabolic pathway
• Glycolysis provides ATP for cellular energy needs
• Glycolysis produces pyruvate for further oxidation in the citric acid cycle (if oxygen is present)
• Glycolysis provides intermediates for other metabolic pathways
• Glycolysis does not require oxygen

Explore Glycolysis, an ancient metabolic pathway used by most organisms to extract energy from glucose. This process splits glucose into two pyruvate molecules through a series of ten enzyme-catalyzed steps in the cytoplasm. Glycolysis occurs in two main phases: energy-requiring and energy-releasing.