Citric Acid Cycle (Krebs Cycle) Summary

Citric Acid Cycle Overview

• Definition and Role in Aerobic Respiration

• The Citric Acid Cycle (CAC), also known as the Krebs Cycle, is a key metabolic pathway that plays a crucial role in aerobic respiration, facilitating the oxidation of acetyl CoA to produce energy.

• Key Reactants and Products

• Reactants:

  • Acetyl CoA

• Products:

  • ATP (energy currency of the cell)
  • NADH (reduced form of nicotinamide adenine dinucleotide)
  • FADH2 (reduced form of flavin adenine dinucleotide)
  • CO2 (carbon dioxide, a waste product)

• Energy Yield from Acetyl CoA

• For each molecule of acetyl CoA entering the cycle:

  • Produces 3 NADH
  • Produces 1 FADH2
  • Produces 1 ATP (via substrate-level phosphorylation)
  • Total of 12 ATP equivalents produced per acetyl CoA when accounting for NADH and FADH2 in the ETC.

Carbon Flow in the Citric Acid Cycle

• Carbon Flow Explanation

• The cycle involves the movement and transformation of carbon atoms:

  • Acetyl CoA (C2) combines with oxaloacetate (C4) to form citrate (C6).
  • Carbon is progressively oxidized and two carbons are released as CO2 (from isocitrate and alpha-ketoglutarate).

• Visualizing Carbon Flow

• Diagrammatic Representation:

  • Glucose → Pyruvate → Acetyl CoA → CAC

• During the cycle, every turn reduces carbon count by releasing CO2.

Role of NADH and FADH2

• Function

• NADH and FADH2 serve as electron donors in the Electron Transport Chain (ETC), essential for ATP production during oxidative phosphorylation.

• Process:

• They donate electrons, which travel through the ETC, creating a proton gradient across the mitochondrial membrane, ultimately leading to ATP synthesis.

Regulation of the Citric Acid Cycle

• Regulatory Mechanisms

• The cycle is regulated by availability of acetyl CoA and feedback mechanisms that include:

  • Enzyme Inhibition:
  • Inhibition of key enzymes such as citrate synthase by NADH, ATP, and citrate, which signal excess products.
  • Activation of pathways by ADP/AMP in response to low energy levels.

• Phosphorylation and Dephosphorylation:

• The regulation of pyruvate to acetyl CoA happens through phosphorylation/dephosphorylation of the pyruvate dehydrogenase (PDH) complex.

Steps of the Citric Acid Cycle

1. Citrate Formation:

• Acetyl CoA + Oxaloacetate ⟶ Citrate
• Enzyme: Citrate Synthase

1. Isomerization:

• Citrate ⟶ Isocitrate (via aconitase)

1. Oxidation and Decarboxylation:

• Isocitrate ⟶ Alpha-ketoglutarate + CO2 + NADH
• Enzyme: Isocitrate Dehydrogenase

1. Further Decarboxylation:

• Alpha-ketoglutarate ⟶ Succinyl CoA + CO2 + NADH
• Enzyme: Alpha-ketoglutarate Dehydrogenase

1. Substrate-level Phosphorylation:

• Succinyl CoA ⟶ Succinate + GTP (or ATP) + CoA
• Enzyme: Succinyl-CoA Synthetase

1. Oxidation:

• Succinate ⟶ Fumarate + FADH2
• Enzyme: Succinate Dehydrogenase

1. Hydration:

• Fumarate ⟶ Malate
• Enzyme: Fumarase

1. Final Oxidation:

• Malate ⟶ Oxaloacetate + NADH

• Enzyme: Malate Dehydrogenase

• Cycle Completion:

• Oxaloacetate can react with another acetyl CoA, continuing the cycle.

Tied Metabolic Pathways

• Metabolic Hub:

• The citric acid cycle not only produces energy but also serves as a hub for converting amino acids and fatty acids into metabolic substrates, highlighting its integrative role in cell metabolism.

• Pathways Involved:

• Intermediates from the CAC can be siphoned off for biosynthesis (e.g., fatty acids, amino acids).

• Citrate's Role in Fatty Acid Synthesis:

• Citrate can be utilized for synthesizing fatty acids when in excess, indicating the cycle's regulatory potential in energy balance.