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 oxidizes pyruvate derivatives to generate ATP, NADH, and FADH2, crucial for energy production and biosynthesis.

Core Principles

• Occurs in the mitochondrial matrix.
• Begins with acetyl-CoA entering the cycle.
• Involves a series of eight enzyme-catalyzed steps.
• Generates CO2 as a waste product.
• Produces electron carriers (NADH and FADH2).
• Yields ATP (or GTP) via substrate-level phosphorylation.
• Regenerates oxaloacetate to continue the cycle.
• Links glycolysis to oxidative phosphorylation.
• Provides precursors for anabolic pathways.

Action Steps

• Pyruvate enters the mitochondria.
• Pyruvate is oxidized to Acetyl-CoA, releasing CO2 and producing NADH.
• Acetyl-CoA combines with oxaloacetate to form citrate.
• Citrate undergoes a series of reactions, releasing CO2 and generating NADH and ATP/GTP.
• The cycle continues through intermediates like isocitrate, alpha-ketoglutarate, succinyl-CoA, succinate, fumarate, and malate.
• Electrons are transferred to NAD+ and FAD, forming NADH and FADH2.
• Oxaloacetate is regenerated to accept another Acetyl-CoA molecule.

Formulas

• $Pyruvate \rightarrow Acetyl-CoA + CO_2 + NADH$
• $Acetyl-CoA + Oxaloacetate \rightarrow Citrate$
• $Citrate \rightarrow Isocitrate \rightarrow \alpha-Ketoglutarate + CO_2 + NADH$
• $\alpha-Ketoglutarate \rightarrow Succinyl-CoA + CO_2 + NADH$
• $Succinyl-CoA \rightarrow Succinate + ATP (or GTP) + CoA$
• $Succinate \rightarrow Fumarate + FADH_2$
• $Fumarate \rightarrow Malate$
• $Malate \rightarrow Oxaloacetate + NADH$

Key Terms

• Acetyl-CoA: A 2-carbon molecule that enters the Citric Acid Cycle, derived from pyruvate oxidation.
• Oxaloacetate: A 4-carbon molecule that combines with Acetyl-CoA to start the cycle and is regenerated at the end.
• Citrate: The first 6-carbon molecule formed in the cycle.
• NADH: An electron carrier molecule that stores energy harvested from oxidation steps.
• FADH2: Another electron carrier molecule, producing less ATP than NADH.
• Substrate-level phosphorylation: Direct synthesis of ATP (or GTP) from a high-energy intermediate.
• Oxidative phosphorylation: ATP synthesis driven by the electron transport chain, using energy from NADH and FADH2.

Real World Examples

• Energy Production: The CAC is central to aerobic respiration, generating the majority of ATP precursors (NADH, FADH2) needed for cellular energy.
• Biosynthesis: Intermediates of the CAC can be diverted to synthesize amino acids, fatty acids, and glucose, supporting cellular growth and repair.

Timeline

• Glycolysis: Glucose is broken down into pyruvate in the cytoplasm.
• Pyruvate Oxidation: Pyruvate enters the mitochondria and is converted to Acetyl-CoA.
• Citric Acid Cycle (CAC): Acetyl-CoA is oxidized in a cyclical series of reactions within the mitochondrial matrix.
• Oxidative Phosphorylation: NADH and FADH2 donate electrons to the electron transport chain, generating a large amount of ATP.

People

• Hans Krebs: Nobel laureate who elucidated the Citric Acid 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 a primary output of the Citric Acid Cycle?: NADH and FADH2