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What is the Mechanism of Glycolysis?

Published in Biochemistry 3 mins read

Glycolysis is a fundamental metabolic pathway that breaks down glucose into pyruvate, generating energy in the form of ATP and NADH. It occurs in the cytoplasm of cells and consists of ten enzymatic reactions divided into two main phases: the energy investment phase and the energy payoff phase.

Phase 1: Energy Investment Phase

This phase consumes ATP to prepare the glucose molecule for subsequent steps.

  1. Hexokinase: Glucose is phosphorylated to glucose-6-phosphate (G6P) using ATP. This reaction is irreversible and commits glucose to the glycolytic pathway.

    • Glucose + ATP → Glucose-6-phosphate + ADP

  2. Phosphoglucose Isomerase: G6P is isomerized to fructose-6-phosphate (F6P).

    • Glucose-6-phosphate ⇌ Fructose-6-phosphate

  3. Phosphofructokinase-1 (PFK-1): F6P is phosphorylated to fructose-1,6-bisphosphate (F1,6BP) using another ATP molecule. This is a key regulatory step.

    • Fructose-6-phosphate + ATP → Fructose-1,6-bisphosphate + ADP

  4. Aldolase: F1,6BP is cleaved into two 3-carbon molecules: glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP).

    • Fructose-1,6-bisphosphate ⇌ Glyceraldehyde-3-phosphate + Dihydroxyacetone phosphate

  5. Triose Phosphate Isomerase: DHAP is isomerized to G3P. This ensures that both products of the previous reaction can proceed through the next steps of glycolysis.

    • Dihydroxyacetone phosphate ⇌ Glyceraldehyde-3-phosphate

At the end of the energy investment phase, one molecule of glucose has been converted into two molecules of glyceraldehyde-3-phosphate, consuming two ATP molecules.

Phase 2: Energy Payoff Phase

This phase generates ATP and NADH.

  1. Glyceraldehyde-3-phosphate Dehydrogenase: G3P is oxidized and phosphorylated by inorganic phosphate to 1,3-bisphosphoglycerate (1,3BPG). NADH is generated in this step.

    • Glyceraldehyde-3-phosphate + NAD+ + Pi ⇌ 1,3-Bisphosphoglycerate + NADH + H+

  2. Phosphoglycerate Kinase: 1,3BPG transfers its high-energy phosphate group to ADP, forming ATP and 3-phosphoglycerate (3PG). This is substrate-level phosphorylation.

    • 1,3-Bisphosphoglycerate + ADP ⇌ 3-Phosphoglycerate + ATP

  3. Phosphoglycerate Mutase: 3PG is converted to 2-phosphoglycerate (2PG).

    • 3-Phosphoglycerate ⇌ 2-Phosphoglycerate

  4. Enolase: 2PG is dehydrated to phosphoenolpyruvate (PEP).

    • 2-Phosphoglycerate ⇌ Phosphoenolpyruvate + H2O

  5. Pyruvate Kinase: PEP transfers its high-energy phosphate group to ADP, forming ATP and pyruvate. This is another substrate-level phosphorylation and a highly regulated step.

    • Phosphoenolpyruvate + ADP → Pyruvate + ATP

At the end of the energy payoff phase, two molecules of glyceraldehyde-3-phosphate have been converted into two molecules of pyruvate, generating four ATP molecules and two NADH molecules. Considering the two ATP molecules consumed in the energy investment phase, the net gain from glycolysis is two ATP molecules and two NADH molecules per glucose molecule.

Reaction Enzyme Reactants Products ATP Used/Produced NADH Produced
1. Phosphorylation Hexokinase Glucose, ATP Glucose-6-phosphate, ADP -1 0
2. Isomerization Phosphoglucose Isomerase Glucose-6-phosphate Fructose-6-phosphate 0 0
3. Phosphorylation Phosphofructokinase-1 (PFK-1) Fructose-6-phosphate, ATP Fructose-1,6-bisphosphate, ADP -1 0
4. Cleavage Aldolase Fructose-1,6-bisphosphate Glyceraldehyde-3-phosphate, DHAP 0 0
5. Isomerization Triose Phosphate Isomerase Dihydroxyacetone phosphate Glyceraldehyde-3-phosphate 0 0
6. Oxidation & Phos. Glyceraldehyde-3-phosphate Dehydrogenase G3P, NAD+, Pi 1,3-Bisphosphoglycerate, NADH + H+ 0 +1
7. ATP Generation Phosphoglycerate Kinase 1,3-Bisphosphoglycerate, ADP 3-Phosphoglycerate, ATP +1 0
8. Isomerization Phosphoglycerate Mutase 3-Phosphoglycerate 2-Phosphoglycerate 0 0
9. Dehydration Enolase 2-Phosphoglycerate Phosphoenolpyruvate, H2O 0 0
10. ATP Generation Pyruvate Kinase Phosphoenolpyruvate, ADP Pyruvate, ATP +1 0
Totals (per glucose) +2 +2

In summary, glycolysis is a ten-step process that breaks down glucose into pyruvate, yielding a net gain of two ATP molecules and two NADH molecules. This pathway is crucial for energy production in many organisms.

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