Krebs Cycle Overview

Introduction to Krebs Cycle

• Also known as the Citric Acid Cycle or Tricarboxylic Acid Cycle.
• Discovered by Hans Adolf Krebs (1900-1981).
• A series of enzymatic reactions utilized by aerobic organisms to generate cellular energy.

Function and Importance

• Central metabolic pathway linking various metabolic pathways.
• Final oxidative pathway for metabolizing carbohydrates, proteins, and fats.
• Oxidizes acetyl CoA to produce CO2, H2O, ATP, and reduced coenzymes (FADH, NADH).

Cellular Respiration

• Process of converting biochemical energy from nutrients into ATP.
• Comprises three main stages, with the Krebs cycle as a key component.

Link Between Glycolysis and Krebs Cycle

• Pyruvate is transported from the cytosol to mitochondria.
• Oxidative decarboxylation of pyruvate forms acetyl-CoA, facilitated by the Pyruvate Dehydrogenase complex.

Pyruvate Dehydrogenase Complex

• Composed of three enzymes and five cofactors.
• Essential for converting pyruvate to acetyl-CoA.
• Deficiency leads to elevated lactate and pyruvate levels, potentially resulting in acidosis and neurological issues.

Cofactors and Their Deficiencies

• Key cofactors: Thiamine (TPP), Niacin (NAD), Riboflavin (FAD), Pantothenic Acid (CoA).
• Thiamine deficiency can cause neurological and cardiac disorders (Beriberi), impairing the oxidation of pyruvate.

Reactions of the TCA Cycle

• Step 1: Formation of citrate through a condensation reaction.
• Step 2: Isomerization to isocitrate.
• Step 3: Formation of α-ketoglutarate (α-KG).
• Step 4: Decarboxylation to succinyl-CoA, generating NADH.
• Step 5: Formation of succinate, producing GTP/ATP via substrate-level phosphorylation.
• Step 6: Conversion to fumarate, inhibited by malonate.
• Step 7: Hydration to malate.
• Step 8: Regeneration of oxaloacetate.

Energy Yield

• Overall reaction generates ATP and reduced coenzymes that drive ATP production in the electron transport chain.
• One cycle of the Krebs cycle yields a total of approximately 10 ATP from one acetyl-CoA.

Regulation of the Krebs Cycle

• Influenced by substrate availability (Acetyl-CoA and oxaloacetate).
• Inhibition by accumulating products and allosteric feedback, particularly a high NADH/NAD+ ratio.
• Covalent modifications can also impact enzyme activity.

Amphibolic Nature

• Serves both catabolic (energy-producing) and anabolic (biosynthetic) functions.
• Involves anaplerotic reactions that replenish intermediates to maintain metabolic balance during varying demands.

Replenishing Pathways

• Specific reactions that restore TCA cycle intermediates, ensuring its continuous operation even when intermediates are diverted for biosynthesis.

Suggested Reading and Resources

• Recommended textbooks include "Lehninger Principles of Biochemistry," "Biochemistry" by Lubert Stryer, and "Biochemistry for Sports and Exercise Science."
• Online videos for visual learning are beneficial.

This quiz covers the essential aspects of the Krebs cycle, including its role in aerobic respiration and its connections to glycolysis. Explore the reactions within the Krebs cycle, its regulation, and its amphibolic nature. Test your understanding of this crucial biochemical pathway.