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Glycolysis and Its Pathways

Glycolysis Overview

  • Glycolysis means "sweet splitting" and takes place in the cytoplasm.

  • It serves as the only source of metabolic energy in certain cells and is crucial for glucose catabolism.

  • Glycolysis includes 10 reactions that occur in all cellular types and produce:

    • 2 molecules of pyruvate

    • 2 ATP

    • 2 NADH

Major Pathways of Glucose Utilization

  • Glucose can be utilized in various pathways:

    • Storage: Glycogen, starch, sucrose

    • Oxidation:

    • Pentose phosphate pathway

    • Glycolysis

  • Ultimately, glycolysis leads to the formation of pyruvate from glucose.

Catabolism of Pyruvate

  • There are three possible fates for pyruvate, depending on the availability of oxygen:

    1. Aerobic Oxidation: Converts to CO₂ and H₂O; enters the citric acid cycle.

    2. Anaerobic Glycolysis: Converts to lactate (e.g., in exercising muscles).

    3. Anaerobic Fermentation: Converts to ethanol (e.g., in yeasts).

Glycolysis Steps

Summary of Glycolysis Phases:

  1. Preparatory Phase (4 steps):

    • Converts one 6C sugar (glucose) to two 3C sugars (glyceraldehyde-3-phosphate and dihydroxyacetone phosphate).

    • Consumes 2 ATP.

  2. Payoff Phase (6 steps):

    • Converts two 3C sugars to two molecules of pyruvate.

    • Produces 4 ATP and 2 NADH.

Detailed Reactions in Glycolysis:

  1. Phosphorylation of Glucose:

    • Converts glucose to glucose-6-phosphate (G-6-P) using ATP (priming reaction).

    • Traps glucose inside the cell because G-6-P does not diffuse out.

  2. Isomerization:

    • Converts glucose-6-P to fructose-6-P (F-6-P); this step is reversible.

  3. Second Phosphorylation:

    • Converts F-6-P to fructose-1,6-bisphosphate (F-1,6-BP); considered the first committed step in glycolysis.

    • This step is highly regulated by PFK1, which is influenced by ATP levels.

  4. Cleavage of Fructose-1,6-BP:

    • Splits into two isomers: dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GAP).

  5. Conversion of DHAP to GAP:

    • Only GAP continues through glycolysis, completing the preparatory phase.

Payoff Phase Summary:

  1. Oxidation of GAP:

    • GAP is oxidized to 1,3-bisphosphoglycerate (1,3-BPG); NAD+ gets reduced to NADH.

  2. Substrate-Level Phosphorylation:

    • 1,3-BPG transfers a phosphoryl group to ADP, forming the first ATP.

  3. Conversion of 3-PG to 2-PG:

    • The enzyme mutase shifts the phosphate group.

  4. Dehydration to PEP:

    • 2-phosphoglycerate (2-PG) is dehydrated to phosphoenolpyruvate (PEP).

  5. Final ATP Production:

    • PEP transfers a phosphoryl group to ADP to produce the second ATP and yields pyruvate.

Overall Glycolysis Reaction

  • The complete glycolysis equation:
    ext{Glucose} + 2 ext{NAD}^+ + 2 ext{ADP} + 2 ext{Pi} \ \ o 2 ext{Pyruvate} + 2 ext{NADH} + 2 ext{ATP} + 2 ext{H}_2 ext{O} + 2 ext{H}^+

  • Net gain of 2 ATP per glucose molecule is achieved, considering 4 ATP produced but 2 are used.

Fate of NADH & Pyruvate

  • Under aerobic conditions:

    • NADH is oxidized in the electron transport chain.

    • Pyruvate enters the citric acid cycle.

  • Under anaerobic conditions:

    • NADH is converted back to NAD+, allowing glycolysis to continue, producing lactate or ethanol depending on cell type.

Fermentation Details

  • Lactic Acid Fermentation: Produces lactate from glucose with a net yield of 2 ATP.

  • Ethanol Fermentation in Yeast: Converts pyruvate to ethanol and CO₂, yielding 2 ATP per glucose.

Clinical Significance

  • Deficiencies in glycolytic enzymes (e.g., hexokinase, pyruvate kinase) can impair oxygen transport in blood, leading to reduced ATP production and altered red blood cell shape.

  • Cancer cells often rely heavily on glycolysis due to their rapid growth and limited oxygen supply, enhancing glucose uptake and glycolytic rates.