05_Glycolysis_Krebs Cycle

Glycolysis and the Krebs Cycle


Page 1: Overview

  • Introduction to Glycolysis and the Krebs Cycle


Page 2: Key Concepts in Thermodynamics

  • Energy Flow

    • Energy flows from one place to another.

    • Energy flows downhill, indicating a natural tendency towards lower energy states.

  • Spontaneous Events

    • Events must be spontaneous, occurring with the release of free energy.

    • Spontaneous does not imply speed; it simply means that reactions can occur without external work.

  • Equilibrium in Enzyme-Catalyzed Reactions

    • Closed systems still reach equilibrium despite catalyst presence.


Page 3: Topics Covered

  • Nutrient Energy Capture

    • Focus on how cells capture free energy from nutrients.

  • Glycolysis

    • Anaerobic pathway for energy generation from glucose.

  • Krebs Cycle

    • The initial aerobic pathway of respiration.

  • Energy Capture Mechanisms

  • Gluconeogenesis

    • Reversal of glycolysis; importance for cellular function.


Page 4: Respiration Summary Equation

  • General Equation:

    • C6H12O6 + 6O2 → 6CO2 + 6H2O

  • Free Energy Change:

    • ΔG0 = -687 kcal/mol

  • ATP Production Potential

    • Theoretical ATP generation from glucose combustion requires understanding ATP hydrolysis energetics.


Page 5: Energy Flow in Living Things

  • Energy Sources:

    1. Visible Light (Photo-autotrophs)

      • Energy captured via photosynthesis; results in chemical energy (glucose).

    2. Nutrient Energy (Oxidative Reactions)

      • Source of energy through chemical fermentation and respiration, generating ATP.

    3. High Energy Intermediates

      • ATP produced coupled with cellular work (e.g., metabolism, growth).


Page 6: ATP Hydrolysis and Cellular Work

  • Hydrolysis vs. Condensation Reaction

    • Hydrolysis releases free energy for cellular work (e.g., movement, synthesis).

  • Nutrient Sources

    • Animal cells derive energy to synthesize ATP solely from nutrients.

    • Photosynthetic organisms utilize sunlight to synthesize nutrients.


Page 7: ATP Generation from Nutrients

  • Glucose Oxidation Reaction:

    • C6H12O6 + 6O2 → 6CO2 + 6H2O

  • Energy Calculations:

    • Encompasses glycolysis, TCA cycle, and electron transport.

    • Approx. 36 ATP + 36 H₂O produced.

    • Total Energy from Glucose: 263 Kcal/mole oxidized.


Page 8: Glycolysis Overview

  • Universal Pathway

    • Present in all organisms; indicates evolutionary significance.

  • Location: Cytosol

  • Breakdown Process

    • Each glucose splits into two pyruvic acid molecules, yielding 2 ATP in the process.

  • Pathway Stages

    • Glycolysis occurs in two stages: energy investment and energy payoff.


Page 9: Glycolysis Process

  • Stage 1: Splitting of Glucose

    • Involves ATP consumption to form intermediates (e.g. fructose-1,6-diphosphate).

  • Stage 2: Production of Pyruvate

    • Involves generation of ATP through substrate-level phosphorylation.

    • Key enzyme: phosphoenolpyruvate to pyruvate, yielding ATP.


Page 10: Pyruvate Fates

  • Anaerobic Metabolism:

    • Produces lactate, alcohol, or dibasic acids via fermentation.

  • Aerobic Metabolism:

    • Further oxidation to CO₂ and H₂0 within mitochondria.


Page 11: Glycolysis Mechanism

  • Reaction 1:

    • Coupled phosphorylation of glucose with ATP hydrolysis; exergonic and irreversible in cells.


Page 12: Hexokinase Energetics

  • Standard Conditions:

    • Glucose phosphorylation as the sum of reactions.

    • Reaction energetics yield an exergonic action with the following values:

    • ATP + G → G-6-P; ΔG < 0 for irreversible phosphorylation.


Page 13: Regulatory Mechanisms

  • Biological Irreversibility:

    • Glucose cannot exit once phosphorylated (by hexokinase).

  • Allosteric Regulation:

    • Glucose-6-Phosphate inhibits hexokinase, conserving cellular resources.


Page 14: Enzymatic Reactions

  • G-6-P Isomerase

    • Mildly endergonic; reversible transformation of glucose-6-phosphate to fructose-6-phosphate.


Page 15: Enzyme Regulation Overview

  • Factors Affecting Enzyme Activity:

    • ATP (inhibitory), ADP (activating), AMP (activating), fatty acids (variable impact).


Page 16: Reactions in Glycolysis

  • F-1,6-DiP Aldolase:

    • Formation of glyceraldehyde-3-phosphate and dihydroxyacetone phosphate; energetically uphill but reversible.


Page 17: Enzyme Regulation and Reaction Dynamics

  • Enzyme, triose-P-isomerase exhibits negative cooperativity regulated by NAD+ concentration for efficient reaction acceleration.


Page 18: Energy Transfer in Glycolysis

  • Exergonic Reaction:

    • Phosphate transfer yielding spontaneous reactions;


Page 19: Mutase Functionality

  • P-glyceromutase:

    • Phosphate group transferring mutases that operate freely and reversibly.


Page 20: End of Glycolysis Reactions

  • Enolase activity with phosphate involves reversible actions; mildly endergonic.


Page 21: Reaction Irreversibility in Glycolysis

  • Highly exergonic, regulated by various metabolites and feedback mechanisms; predict impacts of ATP and intermediates.


Page 22: Efficiency of Pathways

  • Comparison between fermentation and aerobic respiration, highlighting efficiency differences based on NADH and ATP contributions.


Page 23: Introduction to Gluconeogenesis

  • Stored glucose converted to glycogen in well-fed states; controlled by glucagon and insulin.

  • Gluconeogenesis using pyruvate, lactate, glycerol, and amino acids for glucose production.


Page 24: Glycolysis vs. Gluconeogenesis

  • Shared intermediates with distinct pathways; inverse reactions controlled via bypass enzymes to regulate cellular carbohydrate levels.


Page 25: The Cori Cycle

  • Connection between glycolysis and gluconeogenesis.

    • Muscle cells convert glucose to lactate; the liver rejuvenates glucose from lactate through gluconeogenesis.


Page 26: Hormonal Impact on Gluconeogenesis

  • Hormonal regulation from the hypothalamus to control gluconeogenesis through metabolic pathways.


Page 27: Dietary Implications

  • Ultra-low carb diets effect on weight loss and blood sugar control in individuals with type 2 diabetes.

  • Insights into metformin's role in blood sugar regulation.


Page 28: Introduction to Krebs Cycle

  • Significance of oxygen presence for efficient respiration and ATP production; all aerobic organisms including plants utilize the Krebs Cycle.


Page 29: Pyruvate Oxidation

  • Catalyzed by pyruvate dehydrogenase, producing acetyl-S-CoA for the Krebs Cycle; complete oxidation and energy capture mechanisms in the mitochondria.


Page 30: Energy Release from Pyruvate

  • Pyruvate enters mitochondria, initiates the Krebs Cycle; carbon dioxide produced, with energy captured in reduced e- carriers.


Page 31: Free Energy Storage in Respiration

  • Total free energy stored per NADH and FADH2 produced; efficiency of ATP synthesis per glucose oxidized.