Citric Acid Cycle (Krebs Cycle) Cheat Sheet

The Citric Acid Cycle (CAC), also known as the Krebs cycle or TCA cycle, is the second stage of cellular respiration. It occurs in the mitochondria and completes the oxidation of pyruvate to CO2, generating ATP, NADH, and FADH2 for energy production and providing precursors for anabolic pathways.

Core Principles

• The CAC occurs in the mitochondrial matrix.
• It begins with Acetyl-CoA entering the cycle.
• The cycle consists of eight enzyme-catalyzed steps.
• Oxidative reactions release CO2.
• Electrons are transferred to NAD+ and FAD, forming NADH and FADH2.
• NADH and FADH2 are used in oxidative phosphorylation to produce ATP.
• The cycle generates 2 ATP equivalents per glucose molecule via substrate-level phosphorylation.
• It plays a crucial role in connecting carbohydrate, fat, and protein metabolism.
• CAC intermediates can be used as precursors for biosynthesis (anabolic pathways).
• ATP and NADH levels regulate the cycle's speed (feedback inhibition).

Action Steps

• Ensure pyruvate is transported into the mitochondria.
• Convert pyruvate to Acetyl-CoA, releasing CO2 and NADH.
• Acetyl-CoA combines with oxaloacetate to form citrate.
• Proceed through the eight steps of the cycle, catalyzing reactions.
• Release CO2 in specific steps.
• Generate NADH and FADH2 by transferring electrons.
• Produce ATP (or GTP) via substrate-level phosphorylation.
• Regenerate oxaloacetate to continue the cycle.
• Utilize NADH and FADH2 in the electron transport chain for significant ATP production.

Formulas

• Pyruvate (3C) + NAD+ + CoA -> Acetyl-CoA (2C) + CO2 + NADH + H+
• Acetyl-CoA (2C) + Oxaloacetate (4C) -> Citrate (6C) + CoA
• Citrate (6C) -> Isocitrate (6C)
• Isocitrate (6C) + NAD+ -> α-Ketoglutarate (5C) + CO2 + NADH + H+
• α-Ketoglutarate (5C) + NAD+ + CoA -> Succinyl-CoA (4C) + CO2 + NADH + H+
• Succinyl-CoA (4C) + GDP + Pi -> Succinate (4C) + GTP + CoA
• Succinate (4C) + FAD -> Fumarate (4C) + FADH2
• Fumarate (4C) + H2O -> Malate (4C)
• Malate (4C) + NAD+ -> Oxaloacetate (4C) + NADH + H+

Key Terms

• Citric Acid Cycle (CAC): Also known as the Krebs cycle or TCA cycle; the central metabolic pathway that oxidizes acetyl-CoA.
• Acetyl-CoA: A molecule that enters the CAC, formed from pyruvate oxidation.
• Oxaloacetate: The 4-carbon molecule that reacts with Acetyl-CoA to start the cycle and is regenerated at the end.
• NADH: An electron carrier molecule that stores energy from oxidation reactions.
• FADH2: Another electron carrier molecule, similar to NADH.
• Substrate-level phosphorylation: Direct synthesis of ATP from a substrate molecule, occurring in glycolysis and the CAC.
• Oxidative phosphorylation: ATP synthesis driven by the electron transport chain, using energy from NADH and FADH2.
• Anabolic Pathways: Metabolic pathways that build complex molecules from simpler ones, often using CAC intermediates.
• Feedback Inhibition: A regulatory mechanism where the end product of a pathway inhibits an enzyme earlier in the pathway.

Real World Examples

• Cellular energy production: The CAC is essential for generating the majority of ATP in aerobic respiration, powering cellular functions.
• Biosynthesis of amino acids: Intermediates like α-ketoglutarate and oxaloacetate are precursors for synthesizing various amino acids.
• Fatty acid synthesis: Acetyl-CoA, a product of pyruvate oxidation and an input to the CAC, is the primary building block for fatty acids.

Timeline

• Pre-CAC: Glycolysis occurs in the cytosol, breaking glucose into pyruvate.
• Pyruvate Oxidation: Pyruvate enters the mitochondria and is converted to Acetyl-CoA, producing NADH and CO2.
• Step 1: Acetyl-CoA (2C) combines with Oxaloacetate (4C) to form Citrate (6C).
• Steps 2-8: Citrate is isomerized, oxidized, and decarboxylated through a series of reactions, regenerating Oxaloacetate.
• Post-CAC: NADH and FADH2 deliver electrons to the Electron Transport Chain for ATP synthesis.

People

• Hans Krebs: Nobel laureate who discovered the cycle, hence often called the Krebs cycle.

Quiz

• Where does the Citric Acid Cycle take place?: Mitochondrial Matrix
• What molecule directly enters the Citric Acid Cycle?: Acetyl-CoA
• Which of the following is NOT a direct product of the Citric Acid Cycle per Acetyl-CoA molecule?: ATP (or GTP)