U01.01.088 Glycolysis regulation, key enzymes

Glycolysis is a critical metabolic pathway that occurs in the cytoplasm, converting glucose into pyruvate while producing energy in the form of ATP and NADH. It is tightly regulated by key enzymes that control its rate and ensure cellular energy needs are met.

Net Glycolysis Equation (Cytoplasm):

The general reaction for glycolysis is:

Glucose + 2 Pi + 2 ADP + 2 NAD⁺ → 2 Pyruvate + 2 ATP + 2 NADH + 2 H⁺ + 2 H₂O

Note: This equation is not chemically balanced. The exact balance depends on the ionization state of reactants and products.

Key Enzymes in Glycolysis

1. Hexokinase/Glucokinase

Reaction: Converts glucose to glucose-6-phosphate (G6P).
Regulation:
- Inhibited by glucose-6-phosphate (G6P) (for hexokinase).
- Inhibited by fructose-6-phosphate (for glucokinase in the liver).
- Activated by insulin (in the liver via glucokinase).

2. Phosphofructokinase-1 (PFK-1) – Rate-Limiting Step

Reaction: Converts fructose-6-phosphate to fructose-1,6-bisphosphate (F1,6BP).
Regulation:
- Activated by AMP and fructose-2,6-bisphosphate.
- Inhibited by ATP and citrate (high-energy signals).

3. Phosphoglycerate Kinase

Reaction: Converts 1,3-bisphosphoglycerate (1,3-BPG) to 3-phosphoglycerate (3-PG).
Key Note: Produces ATP during this step.

4. Pyruvate Kinase

Reaction: Converts phosphoenolpyruvate (PEP) to pyruvate.
Regulation:
- Activated by fructose-1,6-bisphosphate.
- Inhibited by ATP and alanine.

Glycolysis Regulation Summary in a Table

Enzyme	Reaction	Activators	Inhibitors
Hexokinase/Glucokinase	Glucose → Glucose-6-phosphate	Insulin (glucokinase in liver)	Glucose-6-phosphate (hexokinase)
Phosphofructokinase-1	Fructose-6-phosphate → Fructose-1,6-BP	AMP, Fructose-2,6-bisphosphate	ATP, Citrate
Phosphoglycerate Kinase	1,3-BPG → 3-PG	–	–
Pyruvate Kinase	PEP → Pyruvate	Fructose-1,6-bisphosphate	ATP, Alanine

Points to Remember

Key Regulatory Steps:
- Hexokinase/Glucokinase: The first step in glycolysis, which traps glucose in the cell as glucose-6-phosphate.
- Phosphofructokinase-1 (PFK-1): The rate-limiting step of glycolysis. Regulation is crucial for controlling glycolytic flux.
- Pyruvate Kinase: The final step in glycolysis, producing pyruvate and generating ATP.
Energy Regulation:
- ATP and citrate are inhibitory signals indicating sufficient energy, leading to reduced glycolysis.
- AMP and fructose-2,6-bisphosphate activate the pathway when energy is needed.
Balance Between Synthesis and Breakdown:
- High ATP/low AMP or high citrate → inhibition of glycolysis.
- Low ATP/high AMP or high fructose-2,6-bisphosphate → activation of glycolysis.

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