Lecture 10: Biochemistry 423

Chapters 16-17: Glycolysis and Gluconeogenesis

Learning Objectives

• Glycolysis: Describe ATP generation in glycolysis.
• Fermentations: Explain the importance of NAD+ regeneration.
• Gluconeogenesis: Describe how it is powered and regulated.

Glycolysis Overview

• Stages of Glycolysis:
  • Stage 1: Requires 2 ATP input.
  • Stage 2: Generates 4 ATP, netting 2 ATP per glucose molecule.
  • Produces NADH, an electron transporter.

Key Points

• ATP Generation: Glycolysis converts glucose to pyruvate, generating ATP.
• NAD+ Regeneration: Crucial for glycolysis; regenerated in fermentation.
• Fermentation Types: Converts pyruvate to ethanol or lactic acid for NAD+ regeneration.

Gluconeogenesis Overview

• Primary Site: Liver converts pyruvate to glucose.
• Energy Requirement: Consumes energy by coupling endergonic reactions with favorable ones.
• Pathway Involvement: Uses different enzymes for irreversible steps compared to glycolysis.

Key Reactions

• Pyruvate to Phosphoenolpyruvate: Requires ATP, GTP, and involves decarboxylation.
• Regulatory Differences: Utilizes different enzymes like glucose-6-phosphatase and fructose 1,6-bisphosphatase.

Regulation

Glycolysis Regulation

• Regulatory Enzymes:
  • Hexokinase: Inhibited by glucose 6-phosphate.
  • Phosphofructokinase (PFK): Inhibited by high ATP; activated by AMP.
  • Pyruvate Kinase: Inhibited by ATP; activated by fructose 1,6-bisphosphate.

Muscle vs. Liver

• Muscle: High energy demand regulates glycolysis mainly through ATP levels.
• Liver: Uses glucokinase for glucose trapping; PFK regulated by citrate.

Reciprocal Regulation

• Glycolysis vs. Gluconeogenesis: Coordinated to be active inversely in cells.
• High Glucose: Glycolysis predominates; Low Glucose: Gluconeogenesis predominates.

Fermentation

• Purpose: Regenerates NAD+ to allow glycolysis continuation.
• Limitations: Excess ethanol/lactate can be toxic.

Whole Body Coordination

• Cori Cycle: Lactate from muscle is converted to glucose in the liver for reuse in muscles.

Additional Points

• Energy Balance: More energy required for gluconeogenesis than gained from glycolysis.
• Pathway Coordination: Both processes are tightly regulated based on energy needs and availability.