MH

Glycolysis and Gluconeogenesis Concepts

Glycolysis and Gluconeogenesis

General Concepts

  • Monosaccharide Glucose: A crucial metabolic intermediate in human metabolism.

  • Glycolysis: Pathway converting glucose to pyruvate or lactate, core mechanism for energy production.

  • Gluconeogenesis: Reverses glycolysis, converting lactate or pyruvate back to glucose.

Major Catabolic Pathways

  • Combined pathways of glycolysis and citric acid cycle form the basic energy-yielding mechanisms.

  • Various substrates like amino acids and glycerol feed into glycolysis.

  • Aerobic Conditions: Glycolysis produces pyruvate, converted to acetyl-CoA and CO2 by pyruvate dehydrogenase, then oxidized in TCA cycle.

Glycolysis Pathway Summary

  • Glucose is a primary fuel, rich in potential energy due to reduced carbon.

  • Process Phases:

    • Phase 1: Glucose (6 carbons) → 2 Glyceraldehyde-3-phosphate (3 carbons) using 2 ATP.

    • Phase 2: 2 Glyceraldehyde-3-phosphate → 2 Pyruvate generating 4 ATP.

Key Intermediates and Products of Glycolysis

  • Glycolysis Steps:

    • Glucose converts into 2 Pyruvate with net output:

      • 2 Pyruvate

      • 2 ATP

      • 2 NADH

Glycolysis Parts

Part I: Top Half of Glycolysis

  • Divided for visualization, involves:

    • Five Steps and Enzymes: Converts glucose to G3P.

    • ATP used: 2 ATP equivalents.

    • Final step interconverts DHAP and G3P producing 2 G3P.

Part II: Bottom Half of Glycolysis

  • Also consists of five steps mirroring Part I.

  • Key Step: G3P to 1,3-bisphosphoglycerate produces NADH, enters oxidative phosphorylation for ATP production.

  • ATP Yield:

    • ATP generation occurs at multiple sites, additional 2 ATP produced.

    • Net Yield: 2 ATP and 2 Pyruvate from glycolysis.

Energy Payoff in Glycolysis

  • Glyceraldehyde 3-phosphate dehydrogenase introduces phosphate, produces NADH.

  • Phosphoglycerate kinase reaction: First ATP production via substrate-level phosphorylation.

Energetics of Glycolysis

Standard Free Energies of Hydrolysis

  • Phosphorylation requires energy while dephosphorylation releases energy, ensuring favorable reaction conditions.

Free Energy Changes in Glycolysis and TCA Cycle

  • Key points include:

    • Overall negative free energy change for glucose to CO2 is critical for product formation.

    • Slightly uphill reactions must theoretically release energy for pathway continuity.

    • Validity of free energy data affects reaction predictions.

Glycolysis vs Glyconeogenesis

  • Glycolysis generates 2 ATP, gluconeogenesis requires 6 ATP.

  • Each step in gluconeogenesis corresponds to reversed glycolysis reactions, ensuring ΔG remains negative.

Summary of Aerobic and Anaerobic Glycolysis

  • Aerobic Glycolysis: Two pyruvate yield and potential for additional ATP via NADH.

  • Anaerobic Glycolysis: Converts pyruvate to lactate to regenerate NAD+ without gaining additional ATP.

The Cori Cycle

  • Describes lactate conversion back to glucose post-exercise in liver.

Entry of Other Sugars into Glycolysis

  • Sucrose: Converted to glucose and fructose by invertase.

  • Fructose Integration: Enters via fructokinase, resulting in glyceraldehyde and dihydroxyacetone phosphate.

  • Galactose: Converted to glucose 6-phosphate through a series of reactions involving galactose kinase and UDP-glucose.

Biochemical Regulation of Glycolysis and Gluconeogenesis

  • Reciprocal Regulation: Prevents simultaneous operation of pathways.

  • Enzyme regulation is essential for controlling metabolic processes under different energy requirements.

Energy Charge Formula

  • Measures availability of high-energy phosphates in the cell; governs regulation of glycolysis and gluconeogenesis.

Feedback Mechanisms

  • Negative Feedback: High ATP levels inhibit glycolysis.

  • Positive Feedback: Low energy charge boosts glycolysis activity.

  • Careful regulation ensures metabolic efficiency without wasteful ATP expenditure.