Glycolysis and Krebs Cycle

Overview

The study of glycolysis and the Krebs cycle (also known as the citric acid cycle or TCA cycle) is central to understanding how living cells extract energy from organic molecules. These metabolic pathways are fundamental topics in biochemistry, as they describe the stepwise oxidation of glucose and other substrates to produce ATP, the universal energy currency of the cell.

Energy in Living Systems

Introduction to Cellular Energy

• Energy Transformation: Cells convert radiant energy (from sunlight) into chemical energy via photosynthesis, and chemical energy from organic molecules via cellular respiration.

• Cellular Respiration: The overall reaction for aerobic respiration is:

• Electron Transfer: Electrons from food molecules are transferred by enzymes, gradually releasing energy for cellular work.

Redox Reactions in Metabolism

Oxidation and Reduction

• Oxidation: Loss of electrons or hydrogen atoms from a molecule, resulting in decreased potential energy.

• Reduction: Gain of electrons or hydrogen atoms, increasing potential energy.

• General Redox Reaction:

• Electron Carriers: Molecules such as NAD+ and FAD shuttle electrons during metabolic reactions.

Key Electron Carriers

• NAD+ (Nicotinamide Adenine Dinucleotide):

• FAD (Flavin Adenine Dinucleotide):

• Both serve as coenzymes in many redox reactions, accepting electrons and protons from substrates.

ATP Synthesis

Substrate-Level Phosphorylation

• ATP Formation: Direct transfer of a phosphate group from a phosphorylated intermediate to ADP, forming ATP.

• General Reaction:

• Occurs during glycolysis and the Krebs cycle.

Glycolysis

Pathway Summary

• Location: Cytoplasm of nearly all cells.

• Oxygen Requirement: Can occur with or without oxygen (anaerobic or aerobic).

• Overall Reaction:

• Net Yield: 2 ATP and 2 NADH per glucose molecule.

• Phases:

  1. Energy Investment: 2 ATP consumed.

  2. Cleavage: 6-carbon glucose split into two 3-carbon molecules.

  3. Energy Payoff: 4 ATP and 2 NADH produced.

Key Steps and Enzymes

• Hexokinase: Phosphorylates glucose (Step 1).

• Phosphofructokinase: Major regulatory enzyme (Step 3).

• Pyruvate Kinase: Catalyzes final step, producing ATP and pyruvate.

Regulation of Glycolysis

• Phosphofructokinase (PFK): Allosterically inhibited by ATP and citrate; activated by AMP and ADP.

• Feedback Inhibition: Accumulation of products (ATP, NADH) inhibits key enzymes to prevent excess energy production.

• Allosteric Activation: Low energy signals (AMP, ADP) activate glycolytic enzymes.

Fate of Pyruvate

Pyruvate Oxidation

• Location: Mitochondrial matrix (in eukaryotes).

• Reaction:

• Enzyme: Pyruvate dehydrogenase complex.

• Purpose: Links glycolysis to the Krebs cycle by converting pyruvate to acetyl-CoA.

Fermentation (Anaerobic Conditions)

• Regenerates NAD+: Allows glycolysis to continue in absence of oxygen.

• Types:

  • Lactic Acid Fermentation: Pyruvate reduced to lactate (in animals).

  • Alcoholic Fermentation: Pyruvate converted to ethanol and CO2 (in yeast).

• ATP Yield: Only from glycolysis (2 ATP per glucose).

Krebs Cycle (Citric Acid Cycle)

Pathway Summary

• Location: Mitochondrial matrix.

• Function: Completes oxidation of acetyl-CoA, producing CO2, NADH, FADH2, and GTP/ATP.

• Overall Reaction (per acetyl-CoA):

• Key Steps:

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

  2. Series of oxidation and decarboxylation reactions regenerate oxaloacetate.

  3. Energy captured in NADH, FADH2, and GTP/ATP.

Regulation of Krebs Cycle

• Feedback Inhibition: High levels of ATP, NADH, and acetyl-CoA inhibit cycle enzymes.

• Activation: High levels of ADP, NAD+, and CoA activate cycle enzymes.

Summary Table: Key Metabolic Pathways

Key Concepts and Applications

• Metabolic Pathways: Glycolysis and Krebs cycle are central to energy metabolism in all living cells.

• Regulation: Enzyme activity is tightly regulated by energy status and feedback inhibition.

• Clinical Relevance: Defects in glycolytic or Krebs cycle enzymes can lead to metabolic diseases.

• Research Applications: Understanding these pathways is essential for biotechnology, medicine, and physiology.

Additional info: Some diagrams and images referenced in the original notes (e.g., enzyme structures, mitochondrial membranes) are not reproduced here, but their context is described in the explanations above.