Biochemistry: The Krebs Cycle

Biochemistry: The Krebs Cycle

Chapter Overview

  • Learning Objectives:

    • Understand the big picture of the Krebs Cycle

    • Know about Dr. Hans Krebs and the discovery of the cycle

    • Understand the role of mitochondria in the Krebs Cycle

    • Learn about Coenzyme A and acetyl CoA

    • Examine the steps of the Krebs Cycle

    • Analyze energy extraction during the cycle

    • Review regulation mechanisms of the cycle

The Big Picture

Aerobic Metabolism Overview

  • Three Major Processes:

    1. Citric Acid Cycle

    2. Electron Transport Chain

    3. Oxidative Phosphorylation

  • Important Intermediates:

    • NADH and FADH₂ act as electron carriers during oxidation-reduction reactions.

  • Oxidation steps to push electrons to the transport chain

Key Coenzymes

  • Nicotinamide Adenine Dinucleotide (NAD):

  • Flavin Adenine Dinucleotide (FAD):

The Krebs Cycle Steps

  • Location: Occurs in the mitochondria.

  • Transport Mechanism:

    • Cytosolic pyruvate must cross two mitochondrial membranes:

    • Outer membrane uses porins

    • Inner membrane uses transport proteins.

Coenzyme A

  • Role: Acyl carrier molecule essential for metabolism.

Steps in the Cycle

  1. Condensation: Acetyl-CoA combines with oxaloacetate to form citrate.

  2. Dehydration and Isomerization: Citrate is converted to isocitrate via aconitase.

  3. Oxidative Decarboxylation: Isocitrate converted to alpha-ketoglutarate, producing NADH and CO₂.

  4. Further Decarboxylation: Alpha-ketoglutarate is transformed into succinyl-CoA, generating another NADH and releasing CO₂.

  5. Substrate-Level Phosphorylation: Succinyl-CoA to succinate, forming GTP (or ATP).

  6. Dehydrogenation: Succinate to fumarate generates FADH₂.

  7. Hydration: Fumarate converted to malate.

  8. Final Oxidation: Malate to oxaloacetate produces another NADH.

    • The cycle ends by regenerating oxaloacetate, allowing it to react with another acetyl-CoA.

Energy Extraction from the Krebs Cycle

Summary of Energy Outputs

  • Comparison of energy production:

    • From glucose: 38 ATP total (from glycolysis to oxidative phosphorylation)

    • From 2 Acetyl-CoA: 24 ATP generated via Krebs and electron transport.

  • Table 9.2: Energy Production Breakdown:

    • Process:

    • Glycolysis produces 2 ATP, 2 NADH

    • Krebs Cycle from 2 acetyl-CoA yields 3 NADH, 1 FADH₂, 1 GTP (ATP equivalent).

Regulation of the Krebs Cycle

  • Key Control Points:

    1. Citrate Synthase:

    • Regulated by substrate levels, ATP/ADP ratio, and NADH/NAD⁺ ratio.

    • Inhibited by its product (citrate).

    1. Isocitrate Dehydrogenase:

    • Regulated by substrate availability and NADH/NAD⁺ ratio.

    1. α-Ketoglutarate Dehydrogenase:

    • Regulation by substrate and NADH levels.

Summary Connections: Glycolysis and TCA Cycle

  • Glycolysis and the TCA Cycle are interconnected pathways essential for energy metabolism.

  • They collectively produce pyruvate, which enters the TCA as acetyl-CoA.