Overview of the Krebs Cycle

Overview of the Krebs Cycle

• The Krebs cycle, also known as the citric acid cycle, is a vital metabolic process occurring in the mitochondria of eukaryotic cells.
• It's a series of chemical reactions extracting energy from acetyl-CoA, derived from the breakdown of carbohydrates, fats, and proteins.
• The cycle is central to cellular respiration, extracting energy-rich electrons from organic molecules for the electron transport chain.
• The cycle begins with the combination of acetyl-CoA and oxaloacetate to form citrate.

Key Steps of the Krebs Cycle

• The cycle progresses through eight distinct enzyme-catalyzed reactions.
• Each intermediate is a substrate for the next enzyme reaction.
• Each step involves the release or consumption of small molecules like water or CO2.
• These reactions yield ATP, NADH, and FADH2, used in the electron transport chain for ATP production supporting cellular functions.

Products of the Krebs Cycle

• Per acetyl-CoA processed:
  • 3 NADH (electron carriers)
  • 1 FADH₂ (electron carrier)
  • 1 ATP (directly produced)
  • 2 CO₂ (waste product)
• The cycle regenerates oxaloacetate to accept more acetyl-CoA molecules.

Importance of the Krebs Cycle

• The Krebs cycle is crucial for cellular energy production through cellular respiration.
• It produces vital intermediates for anabolic pathways like amino acid, lipid, and other molecule synthesis.
• The cycle is essential for metabolism, breaking down carbohydrates, fats, and proteins for ATP.
• It provides building blocks (intermediates) for the synthesis of non-essential amino acids and other molecules.

Regulation of the Krebs Cycle

• The Krebs cycle is regulated by substrate, product levels and cellular needs.
• Regulatory enzymes respond to energy charge (ATP/ADP ratio) and substrate availability.
• High ATP and NADH inhibit the cycle, signaling sufficient energy and excess electrons.

Clinical Significance

• Krebs cycle dysfunctions lead to metabolic disorders.
• Deficiencies in enzymes cause toxic intermediate build-up and vital cofactor depletion, harming energy production.
• Conditions impacting the cycle manifest as muscle weakness, poor growth, and neurological problems.
• Understanding the cycle is crucial for treatments of enzyme deficiencies and metabolic diseases.

Relationship to other Metabolic Pathways

• The Krebs cycle connects with other metabolic pathways.
• It receives acetyl-CoA from glycolysis (carbohydrates) and fatty acid oxidation (fats).
• It provides precursors for amino acid, porphyrin, and other molecule synthesis.
• The cycle is a key link between carbohydrate, fat, and protein metabolism.