Overview
This section explains how pyruvate is oxidized to acetyl CoA and how the citric acid cycle (Krebs cycle) operates to harvest energy from glucose during cellular respiration.
Pyruvate Oxidation
- In eukaryotes, pyruvate from glycolysis enters the mitochondria for further oxidation.
- Pyruvate is converted to acetyl CoA in a three-step process: decarboxylation, oxidation, and transfer to CoA.
- One carbon is removed from pyruvate as CO₂, producing a two-carbon acetyl group.
- The acetyl group is oxidized, reducing NAD⁺ to NADH.
- The resulting acetyl group binds to coenzyme A, forming acetyl CoA.
- This process occurs twice per glucose molecule because glycolysis produces two pyruvate molecules.
The Citric Acid Cycle (Krebs Cycle)
- The citric acid cycle occurs in the mitochondrial matrix and is a circular (closed loop) pathway.
- Acetyl CoA donates its acetyl group to oxaloacetate, forming citrate.
- The cycle completes a series of redox, dehydration, hydration, and decarboxylation reactions.
- Each cycle turn releases two CO₂, produces three NADH, one FADH₂, and one GTP/ATP.
- Most ATP production is indirect, via NADH and FADH₂ for the electron transport chain.
- The cycle is aerobic because NADH and FADH₂ must transfer electrons to oxygen-dependent pathways.
- The last step regenerates oxaloacetate, allowing the cycle to continue.
Regulation and Functions
- The first step is highly exergonic and regulated by negative feedback from ATP.
- Intermediate steps are also regulated by ATP, NADH, ADP, and succinyl CoA.
- The cycle is amphibolic; some intermediates are used to make nonessential amino acids.
Key Terms & Definitions
- Pyruvate — 3-carbon molecule produced by glycolysis.
- Acetyl CoA — 2-carbon molecule attached to coenzyme A, enters the citric acid cycle.
- Coenzyme A (CoA) — Carrier molecule derived from vitamin B5 for acetyl groups.
- Citric acid cycle/Krebs cycle/TCA cycle — Pathway that oxidizes acetyl CoA, releasing CO₂ and generating NADH, FADH₂, and ATP/GTP.
- NADH/FADH₂ — Electron carriers that transport energy to the electron transport chain.
- Oxaloacetate — 4-carbon molecule that combines with acetyl CoA to start the cycle.
- Amphibolic — Pathway that is both catabolic and anabolic.
Action Items / Next Steps
- Review the steps and regulation of the citric acid cycle.
- Study how NADH and FADH₂ contribute to ATP production in the electron transport chain.
- Watch the recommended animation of the citric acid cycle.