Glycolysis Regulation and Key Enzymes

Sep 3, 2024

Regulation of Glycolysis Lecture Notes

Overview

  • In-depth analysis of glycolysis regulation.
  • Focus on three key enzymes: Hexokinase, Phosphofructokinase-1, and Pyruvate Kinase.
  • Discussion on substrates and hormones influencing glycolysis.

Key Enzymes

  1. Hexokinase

    • Converts glucose into glucose 6-phosphate.
    • Found in most body cells (specifically hexokinase type 2 in muscles).
    • Stimulated by glucose and inhibited by glucose 6-phosphate (allosteric regulation).
    • Glucokinase: Found in liver, regulated by glucose (stimulates) and fructose 6-phosphate (inhibits).
    • Hormonal regulation by insulin (stimulates synthesis) and glucagon (inhibits activity).

  2. Phosphofructokinase-1 (PFK-1)

    • Catalyzes the conversion of fructose 6-phosphate to fructose 1,6-bisphosphate.
    • Highly regulated step in glycolysis.
    • Inhibited by high ATP and citrate (indicates high energy supply).
    • Stimulated by high ADP and fructose 2,6-bisphosphate.
    • Fructose 2,6-bisphosphate is the most powerful regulator, produced via PFK-2.
    • PFK-2 and FBPase-2 (bifunctional enzyme) are regulated by insulin (stimulates PFK-2) and glucagon (stimulates FBPase-2).

  3. Pyruvate Kinase

    • Final step converting phosphoenolpyruvate (PEP) to pyruvate.
    • Inhibited by high ATP, long-chain fatty acyl-CoAs, and acetyl-CoA (indicate ample energy supply).
    • Stimulated by insulin (increases synthesis) and fructose 1,6-bisphosphate (feed-forward activation).
    • Inhibited by glucagon through phosphorylation.

Regulation Types

  • Allosteric Regulation: Molecules bind at sites other than the active site to modulate enzyme activity.
  • Hormonal Regulation: Involves phosphorylation/dephosphorylation affecting enzyme activity or abundance.

Clinical Correlation

  • Glyceraldehyde-3-phosphate Dehydrogenase & Pyruvate Kinase
    • Inhibition by arsenate, which competes with phosphate binding, disrupting glycolysis.

Summary

  • Glycolysis regulation is complex, involving multiple layers of control to ensure energy balance.
  • Important for cellular metabolism, energy homeostasis, and adaptation to varying conditions.

These notes contain the essential points discussed in the lecture on glycolysis regulation, focusing on enzyme regulation, mechanisms of action, and the physiological relevance in metabolic pathways.