(1) Krebs Cycle | Made Easy!

Overview of the Krebs Cycle

  • Also known as the citric acid cycle or tricarboxylic acid (TCA) cycle.

Recap of Glycolysis

  • Glycolysis converts glucose (C6H12O6) into two three-carbon molecules (pyruvate).

  • Net Gain from Glycolysis:

    • 2 NADH molecules.

    • 2 ATP molecules.

  • Purpose: Generate ATP directly or indirectly through NADH/FADH2 for the subsequent processes in cellular respiration (Krebs cycle and electron transport chain).

Transition from Glycolysis to Krebs Cycle

  • Pyruvate, a three-carbon molecule, enters the mitochondria but needs to be converted to acetyl-CoA to pass through its membranes.

  • Conversion Process:

    • Lose one carbon (released as CO2).

    • Add coenzyme A (CoA) to form acetyl-CoA.

    • NAD+ is reduced to NADH in this reaction.

Importance of B Vitamins

  • Different vitamins are necessary for the conversion of pyruvate to acetyl-CoA:

    • Thiamine pyrophosphate (TPP): derivative of Vitamin B1.

    • Coenzyme A: requires pantothenic acid (Vitamin B5).

    • NAD+: derived from niacin (Vitamin B3).

  • Enzyme Used: Pyruvate dehydrogenase.

Acetyl-CoA Entry into the Krebs Cycle

  • Acetyl-CoA (two carbons) binds to the four-carbon molecule oxaloacetate (OAA) to form citrate (six carbons) through the enzyme citrate synthase.

  • CoA is released during this reaction.

Citrate Rearrangement

  • Citrate rearranges to form isocitrate using water with the help of the enzyme aconitase.

Conversions in the Krebs Cycle

  1. Isocitrate to Alpha-Ketoglutarate (5 carbons):

    • Carbon is lost as CO2.

    • NAD+ is reduced to NADH.

    • Enzyme: Isocitrate dehydrogenase.

  2. Alpha-Ketoglutarate to Succinyl-CoA (4 carbons):

    • Another carbon is lost as CO2, and CoA is gained.

    • NAD+ is reduced to NADH.

    • Enzyme: Alpha-ketoglutarate dehydrogenase.

  3. Succinyl-CoA to Succinate:

    • CoA is released; energy is produced, enabling the conversion of ADP to ATP (or GDP to GTP).

    • Enzyme: Succinyl-CoA synthetase.

  4. Succinate to Fumarate:

    • FAD is reduced to FADH2 through the enzyme Succinate dehydrogenase.

  5. Fumarate to Malate:

    • Water is added using the enzyme Fumarase.

  6. Malate to Oxaloacetate:

    • NAD+ is reduced to NADH again via the enzyme Malate dehydrogenase.

Summary of Outcomes from Krebs Cycle

  • For each glucose molecule (yielding two pyruvate):

    • 4 CO2 produced.

    • 6 NADH produced.

    • 2 FADH2 produced.

    • 2 ATP produced (directly).

Substrate Flexibility of the Krebs Cycle

  • Amino Acids: Can enter or exit at various points in the cycle, e.g., alpha-ketoglutarate can lead to amino acid synthesis.

  • Fatty Acids: Can convert to acetyl-CoA and interact with the cycle.

Impact of Glucose Deprivation

  • Without glucose, oxaloacetate can transform into malate and then into glucose.

  • If acetyl-CoA is produced without oxaloacetate (due to glucose absence), it accumulates and forms ketones (ketogenesis).

  • Ketones can then be used by the brain for energy (after conversion back to acetyl-CoA).

Conclusion

  • The Krebs cycle is essential in cellular respiration, producing energy carriers (NADH, FADH2) and ATP necessary for further energy production in the electron transport chain.