High-Yield Biochemistry Series: Glycolysis

Introduction

• Presenter: Dirty Medicine
• Topic: Glycolysis
• Significance: First biochemical pathway learned in biochemistry; high-yield for exams.
• Goals: Understand function, reactants/products, regulatory mechanisms, rate-limiting enzyme.

Overview of Glycolysis

• Location: Occurs in the cytoplasm.
• Net Equation: Glucose + 2 ATP + 2 NAD+ → 2 Pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 Water
• Purpose: Breaks down glucose into products usable in other pathways, primarily citric acid cycle.

Key Steps in Glycolysis

1. Glucose to Glucose 6-Phosphate

   • Enzymes: Glucokinase and Hexokinase
   • Glucokinase:
     • Low affinity (High Km)
     • Acts as glucose sensor in liver and pancreatic beta-cells
     • Used in high glucose concentration
   • Hexokinase:
     • High affinity (Low Km)
     • Maintains basal glucose metabolism
     • Converts glucose throughout the body

2. Glucose 6-Phosphate to Fructose 6-Phosphate

3. Fructose 6-Phosphate to Fructose 1,6-Bisphosphate

   • Rate-Limiting Enzyme: Phosphofructokinase-1 (PFK-1)
   • Regulation:
     • Inhibited by: ATP, Citrate
     • Promoted by: AMP

4. Fructose 6-Phosphate Side Step

   • Can become Fructose 2,6-Bisphosphate via Phosphofructokinase-2 (PFK-2)
   • PFK-2 Regulation:
     • Inhibited by: Glucagon
     • Promoted by: Insulin
   • Fructose 2,6-Bisphosphate promotes PFK-1, accelerating glycolysis.

5. Phosphoenolpyruvate to Pyruvate

   • Enzyme: Pyruvate Kinase
   • Inhibition: ATP, Citrate (same rationale as PFK-1)

Important Enzymes & Regulatory Mechanisms

• Rate-Limiting Enzymes: Phosphofructokinase-1 (PFK-1), Pyruvate Kinase
• Inhibitors: ATP, Citrate
• Promoters: AMP, Insulin (for PFK-2)

Summary

• Focus on rate-limiting enzymes and regulatory mechanisms.
• Differentiate between Glucokinase and Hexokinase.
• Understand the big picture of glycolysis for regulatory context.

Exam Strategy

• Know enzymes and regulatory mechanisms.
• Use intuition about pathway goals to deduce inhibition/promotion.
• Additional enzymes and steps are not typically required for exams.

Outro

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• Good luck on exams!