Detailed Study Notes on the Krebs Cycle

Overview of the Krebs Cycle

  • The Krebs Cycle, also known as the Citric Acid Cycle, is a crucial part of cellular respiration that follows glycolysis.

Glycolysis

  • Begins with glucose, leading to energy investment and energy payoff phases.

  • Energy Investment Phase: Requires two molecules of ATP to energize and destabilize glucose, allowing it to split into two molecules of glyceraldehyde-3-phosphate (G3P) or 2-phosphoglycerate (2PG).

  • Energy Payoff Phase: Involves the oxidation of G3P allowing for the reduction of NAD+ to NADH, and later producing ATP through phosphorylation reactions.

  • Products of Glycolysis:

    • 2 pyruvate molecules

    • 2 ATP molecules

    • 2 NADH molecules

  • Energy Content:

    • Glucose provides approximately 686 kilocalories per mole.

    • ATP provides approximately 7.2 - 7.4 kilocalories per mole, representing about 1% of the energy found in glucose.

  • Glycolysis is inefficient as it extracts only 2% of glucose energy, leaving 98% unutilized, primarily stored in pyruvate and NADH.

Energy Considerations with Glycolysis

  • Majority of energy in glucose is contained within the pyruvate molecule.

  • Energy release is somewhat controlled, preventing loss of energy as heat and maximizing efficiency for cellular work.

  • Complete breakdown of glucose leads to carbon dioxide, an endpoint with low energy extraction.

Mitochondria and Cellular Respiration

  • Locations:

    • Glycolysis occurs in the cytoplasm

    • Krebs Cycle takes place in the mitochondria, specifically within the matrix.

  • Structure of Mitochondria:

    • Double membrane structure (outer and inner membrane).

    • The inner membrane (cristae) is highly folded, increasing surface area for reactions.

    • The space within the inner membrane: matrix, functions like the stroma in chloroplasts.

    • Intermembrane space analogous to thylakoid lumen in chloroplasts.

  • Origin: Mitochondria are believed to have arisen through endosymbiosis, possessing their own ribosomes and DNA.

Link Reaction

  • Occurs between glycolysis and the Krebs Cycle.

  • Converts pyruvate (three-carbon) into acetyl CoA (two-carbon), which feeds into the Krebs cycle.

  • Decarboxylation Reaction: Removes one carbon from pyruvate as carbon dioxide (CO2).

    • Reduction of NAD+ to NADH occurs, indicating an oxidation-reduction process.

  • This reaction initiates the dismantling of the sugar and links glycolysis to the Krebs cycle.

Krebs Cycle (Citric Acid Cycle)

  • Commences with Acetyl CoA (derived from the Link Reaction) combining with Oxaloacetate (four-carbon compound) to form Citrate (six-carbon compound).

Key Reactions in the Krebs Cycle

  1. Citrate to Isocitrate:

    • Rearrangement reaction (isomerization).

  2. Isocitrate to Alpha-Ketoglutarate:

    • Decarboxylation: CO2 released, NAD+ reduced to NADH.

  3. Alpha-Ketoglutarate to Succinyl CoA:

    • Another decarboxylation: CO2 released, NAD+ reduced to NADH.

  4. Succinyl CoA to Succinate:

    • Substrate-level phosphorylation occurs; ATP (or GTP) is produced.

  5. Succinate to Fumarate:

    • Oxidation reaction: FAD is reduced to FADH2.

  6. Fumarate to Malate:

    • Simple hydration reaction.

  7. Malate to Oxaloacetate:

    • Oxidation reaction: NAD+ reduced to NADH.

Products of the Krebs Cycle (per cycle)

  • For every Acetyl CoA (hence, two cycles per glucose):

    • 2 CO2 (since each glucose yields two Acetyl CoA)

    • 1 ATP (from substrate-level phosphorylation)

    • 3 NADH (reduced each time NAD+ is reduced)

    • 1 FADH2 (reduced from FAD)

Total Count from One Glucose

  • Outputs for two complete cycles:

    • 6 CO2 (as glucose has 6 carbons)

    • 2 ATP

    • 8 NADH

    • 2 FADH2

Efficiency and Energy Yield

  • Total energy yield from glycolysis and Krebs Cycle (ATP production percentage)

    • 4% of glucose energy results in usable ATP (4 out of 686 kcal).

    • The Krebs cycle is not primarily an ATP-producing pathway but focuses on generating NADH and FADH2 for later ATP synthesis through oxidative phosphorylation.

Conclusion

  • The Krebs cycle efficiently dismantles sugar, extracting energy associated with hydrogen and electrons bound to NADH and FADH2.

  • Understanding this metabolic sequence is critical to understand overall cellular respiration and energy production.