Glycolysis refers to the sequence of reactions that convert glucose into pyruvate or lactate while producing ATP. Researchers fully elucidated this pathway in 1940, and today we commonly call it the Embden–Meyerhof Pathway (EMP).
Salient Features of Glycolysis
- All enzymes of the pathway function in the cytosol.
- Glycolysis proceeds in two forms:
- Anaerobic glycolysis, which produces lactate without oxygen
- Aerobic glycolysis, which forms pyruvate when oxygen is available
- Cells that lack mitochondria—such as erythrocytes, cornea, and lens—depend heavily on glycolysis for ATP.
- Overall reaction: Glucose + 2 ADP + 2 Pi → 2 Lactate + 2 ATP
- Glycolysis supplies several intermediates that feed other metabolic pathways.
- When glycolysis reverses and uses alternate bypass steps, the cell synthesizes glucose through gluconeogenesis.
Phases of Glycolysis
Glycolysis occurs in three major stages. Because each stage contributes differently, understanding them improves conceptual clarity.
1. Priming Stage (Energy Investment Phase)
In this phase, the cell invests ATP to prepare glucose for further breakdown.
- Hexokinase phosphorylates glucose to form glucose-6-phosphate (G6P). This step requires ATP and Mg²⁺, and it traps glucose inside the cell.
- Next, phosphofructokinase (PFK) converts fructose-6-phosphate into fructose-1,6-bisphosphate (F1,6BP). Because this is the committed step of glycolysis, it plays a major regulatory role.
2. Splitting Phase
During this stage, the cell splits the 6-carbon sugar into two 3-carbon molecules.
- Aldolase cleaves F1,6BP into glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP).
- Triose phosphate isomerase rapidly converts DHAP to another molecule of G3P. As a result, both molecules continue through the pathway.
3. Energy Generation Phase
This phase generates ATP, NADH, and the final products—pyruvate or lactate.
- Glyceraldehyde-3-phosphate dehydrogenase converts G3P into 1,3-bisphosphoglycerate (1,3-BPG) while reducing NAD⁺ to NADH.
- Phosphoglycerate mutase (PGM) shifts the phosphate group, converting 3-phosphoglycerate (3-PG) to 2-phosphoglycerate (2-PG).
- Phosphoglycerate kinase transfers a phosphate from 1,3-BPG to ADP, forming the first molecule of ATP through substrate-level phosphorylation.
- Enolase, which fluoride strongly inhibits, converts 2-PG into phosphoenolpyruvate (PEP).
- Finally, pyruvate kinase transfers phosphate from PEP to ADP, forming another ATP and producing pyruvate.
In anaerobic tissues, lactate dehydrogenase reduces pyruvate to lactate. This step regenerates NAD⁺, allowing glycolysis to continue even when oxygen is unavailable.
Tissues such as erythrocytes and exercising muscle rely heavily on this mechanism.
Regulation of Glycolysis
Glycolysis responds quickly to cellular energy needs. Three enzymes play the major regulatory roles, and each enzyme changes activity depending on the metabolic state.
1. Hexokinase
- Hexokinase converts glucose to G6P and prevents its escape from the cell.
- Because glucose inhibits hexokinase, the enzyme maintains balance between glucose influx and utilization.
2. Phosphofructokinase (PFK)
- PFK controls the rate-limiting step of glycolysis.
- ATP and citrate inhibit PFK, whereas AMP and fructose-2,6-bisphosphate (F2,6BP) activate it.
- Since F2,6BP strongly stimulates PFK, it significantly increases glycolytic flux.
3. Pyruvate Kinase
- Pyruvate kinase forms ATP and pyruvate in the final step of glycolysis.
- ATP inhibits the enzyme, and F1,6BP activates it through feed-forward regulation.
- The enzyme exists in active and inactive forms based on phosphorylation.
- Dephosphorylated form = active
- Phosphorylated form = inactive
- Hormonal mechanisms, including cAMP-dependent protein kinase, regulate these states.
Summary
Glycolysis remains a central metabolic pathway because it rapidly converts glucose into ATP, pyruvate, lactate, and key biochemical intermediates. Since tissues can run glycolysis both with and without oxygen, the pathway ensures continuous energy supply across diverse physiological conditions.
Engage with Us:
Stay tuned for more captivating insights and News . Visit our Blogs and Follow Us on social media to never miss an update. Together, let’s unravel the mysteries of the natural world.
