Note 23 - The Krebs Cycle - Reading

Cellular Respiration Overview

Pyruvate Oxidation

  1. Decarboxylation Reaction:

    • A carboxyl group is removed from pyruvate as CO2, catalyzed by the enzyme pyruvate decarboxylase.

  2. Oxidation of Pyruvate:

    • The remaining two-carbon compound undergoes oxidation by NAD+, producing acetic acid (acetate) and forming NADH. This is a redox reaction where pyruvate is oxidized and NAD+ is reduced.

  3. Formation of Acetyl-CoA:

    • Acetate binds with coenzyme A (CoA) to form acetyl-CoA, which is important for further oxidation in the Krebs cycle. CoA is derived from vitamin B5 (pantothenic acid).

Overall Reaction for Pyruvate Oxidation

  • 2 pyruvate + 2 NAD+ + 2 CoA → 2 acetyl-CoA + 2 NADH + 2 H+ + 2 CO2

Role of Acetyl-CoA

  • Acetyl-CoA is versatile, central to energy metabolism, feeding into the Krebs cycle or anabolic pathways (fat synthesis) depending on ATP levels. Low ATP leads to Krebs cycle entry; high ATP funnels acetyl-CoA towards lipid production.

The Krebs Cycle

Discovery and Background

  • Sir Hans Krebs discovered the Krebs cycle in 1937 and won the Nobel Prize in 1953. The cycle is a series of eight enzyme-catalyzed reactions that transforms energy stored in organic molecules.

Cycle Mechanism

  1. Acetyl-CoA Condensation:

    • Acetyl-CoA (2-C) combines with oxaloacetate (4-C) to form citrate (6-C).

  2. Rearrangement and Reactions:

    • Citrate → Isocitrate → α-Ketoglutarate (CO2 removed, NAD+ reduced).

    • α-Ketoglutarate → Succinyl-CoA (another CO2 removed, NAD+ reduced).

    • Succinyl-CoA → Succinate (ATP formed through substrate-level phosphorylation).

    • Succinate → Fumarate → Malate (FAD reduced to FADH2).

    • Malate → Oxaloacetate (NAD+ reduced).

Overall Reaction for the Krebs Cycle

  • Oxaloacetate + Acetyl-CoA + ADP + Pi + 3 NAD+ + FAD → ATP + 3 NADH + 3 H+ + FADH2 + 2 CO2 + oxaloacetate

  • The cycle is referred to as the citric acid cycle or tricarboxylic acid (TCA) cycle due to the nature of the compounds generated.

Key Features of the Krebs Cycle

  • Takes place twice per glucose molecule as two acetyl-CoA are formed from one glucose.

  • Energy harvesting occurs at steps 3, 4, 5, 6, and 8, primarily reducing NAD+ to NADH and through ATP formation via substrate-level phosphorylation.

  • Final carbon atoms are released as CO2, showcasing the complete oxidation of the original glucose.

Electron Transport Chain (Stage 4)

  • The reduced coenzymes NADH and FADH2 transfer electrons to the electron transport chain (ETC), leading to ATP production via oxidative phosphorylation. Each ETC component is arranged by increasing electronegativity. This process is crucial for generating the majority of ATP during cellular respiration.