Metabolism | Glycolysis

Introduction

This tutorial provides a comprehensive overview of glycolysis, a crucial metabolic pathway that converts glucose into pyruvate, generating energy in the form of ATP. Understanding glycolysis is essential for students of biochemistry and anyone interested in cellular metabolism. We will break down the ten steps of glycolysis, the enzymes involved, and the byproducts produced during this process.

Step 1: Understand Glucose Transporters

• Glucose enters the cell via specific transport proteins known as glucose transporters (GLUT).
• There are several types of GLUT, each with different tissue distributions and roles.
• Ensure to identify the primary GLUT used in your cell type, as it affects how glucose is taken up.

Step 2: Formation of Glucose-6-Phosphate

• Once inside the cell, glucose is phosphorylated to form glucose-6-phosphate (G6P) by the enzyme hexokinase.
• This step is crucial as it traps glucose in the cell and prepares it for further metabolism.
• Remember, G6P is an important branch point in metabolism, leading to glycolysis, glycogenesis, or the pentose phosphate pathway.

Step 3: Conversion to Fructose-6-Phosphate

• G6P is converted to fructose-6-phosphate (F6P) by the enzyme phosphoglucose isomerase.
• This is an isomerization reaction, meaning the structure of the molecule is rearranged without adding or removing anything.

Step 4: Phosphorylation to Fructose-1,6-Bisphosphate

• F6P is phosphorylated to fructose-1,6-bisphosphate (F1,6BP) by phosphofructokinase-1 (PFK-1).
• This step is a key regulatory point in glycolysis, controlling the pathway's flow based on the cell's energy needs.

Step 5: Cleavage into Two Three-Carbon Sugars

• The enzyme aldolase cleaves F1,6BP into two three-carbon molecules: dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P).
• Both molecules are interconvertible, but G3P continues in the glycolytic pathway while DHAP can be converted to G3P if needed.

Step 6: Conversion of G3P

• G3P is further processed by glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to form 1,3-bisphosphoglycerate (1,3-BPG).
• This step involves the reduction of NAD+ to NADH, capturing energy.

Step 7: Formation of 3-Phosphoglycerate

• 1,3-BPG is converted to 3-phosphoglycerate (3-PG) by phosphoglycerate kinase.
• This reaction generates ATP through substrate-level phosphorylation, highlighting the pathway's energy-yielding aspect.

Step 8: Conversion to 2-Phosphoglycerate

• The enzyme phosphoglycerate mutase converts 3-PG into 2-phosphoglycerate (2-PG).
• This step rearranges the position of the phosphate group.

Step 9: Formation of Phosphoenolpyruvate

• Enolase catalyzes the conversion of 2-PG to phosphoenolpyruvate (PEP), releasing water.
• PEP is a high-energy intermediate, poised for the final step of glycolysis.

Step 10: Production of Pyruvate

• Pyruvate kinase catalyzes the conversion of PEP into pyruvate, generating another ATP molecule.
• This step is another key regulatory point and can be influenced by the energy state of the cell.

Step 11: Anaerobic Conditions

• Under anaerobic conditions, pyruvate can be further converted into lactate (in animals) or ethanol (in yeast) through fermentation.
• This process allows glycolysis to continue in the absence of oxygen by regenerating NAD+.

Conclusion

Glycolysis is a fundamental metabolic pathway that provides energy and building blocks for cellular processes. By understanding each step and the enzymes involved, you gain insights into cellular metabolism and energy regulation. As a next step, consider exploring the Krebs cycle, which follows glycolysis and continues the energy extraction process from pyruvate.