AP Syllabus focus:
‘In mitochondria, pyruvate oxidation and the Krebs cycle release electrons, reduce NAD+ and FAD, and release carbon dioxide.’
Pyruvate oxidation and the Krebs cycle form the central “link” between glycolysis and later energy-harvesting steps. They extract high-energy electrons, store them in reduced coenzymes, and release carbon dioxide as carbon is fully oxidised.
Where and why these reactions happen
In eukaryotic cells, pyruvate oxidation and the Krebs cycle (citric acid cycle) occur in the mitochondrial matrix, where enzymes are positioned to rapidly transfer carbon fragments and electrons.
These stages:
Convert pyruvate (3C) into acetyl-CoA (2C), enabling entry into the cycle
Oxidise the acetyl group to CO₂
Transfer released electrons to NAD⁺ and FAD, forming NADH and FADH₂
Pyruvate oxidation (the link reaction)
Pyruvate produced by glycolysis is processed by a multi-enzyme complex. This is not part of the Krebs cycle, but it supplies the cycle’s input molecule.
Acetyl-CoA: A two-carbon acetyl group bound to coenzyme A; the activated carrier that delivers carbon into the Krebs cycle for oxidation.
Key events (per pyruvate):
Decarboxylation: one carbon is removed as CO₂
Oxidation: remaining 2-carbon fragment is oxidised; NAD⁺ is reduced to NADH
CoA attachment: the 2-carbon acetyl group binds coenzyme A, forming acetyl-CoA
A compact way to track reactants and products is:
Reaction scheme for the pyruvate dehydrogenase complex (pyruvate oxidation), showing oxidative decarboxylation of pyruvate to form acetyl‑CoA. It highlights the release of and the reduction of to , matching the net electron-capture and carbon-loss outcomes described in the link reaction. Source
= reduced electron carrier produced; relative yield per pyruvate (molecules)
Because one glucose yields two pyruvate, pyruvate oxidation happens twice per glucose, producing 2 CO₂ and 2 NADH total.
The Krebs cycle: oxidising acetyl-CoA to CO₂
The Krebs cycle is a cyclical pathway that begins when acetyl-CoA (2C) combines with oxaloacetate (4C) to form citrate (6C).
Overview diagram of the citric acid (Krebs) cycle, organized as eight enzyme-catalyzed steps from citrate formation through regeneration of oxaloacetate. The figure annotates where is released and where electron carriers are reduced (multiple steps and one step), alongside substrate-level phosphorylation producing ATP/GTP. Source
Through a sequence of enzyme-catalysed steps, citrate is rearranged and oxidised, releasing CO₂ and regenerating oxaloacetate so the cycle can continue.
Carbon tracking and CO₂ release
The two carbons entering as the acetyl group are not necessarily the same carbons released as CO₂ in the first turn; however, two CO₂ are released per acetyl-CoA oxidised
Over repeated turns, continued oxidation results in complete conversion of incoming carbon to CO₂
Electron capture: reducing NAD⁺ and FAD
A major purpose of the cycle is capturing high-energy electrons:
NAD⁺ is reduced to NADH at multiple oxidation steps
FAD is reduced to FADH₂ during oxidation of succinate to fumarate (a step associated with an enzyme embedded in the inner mitochondrial membrane)
Schematic of mitochondrial Complex II (succinate dehydrogenase), illustrating electron transfer from succinate through FAD/FADH and iron–sulfur centers to ubiquinone (Q). This visual supports why (not ) is reduced at the succinate→fumarate step and why the enzyme is membrane-associated rather than freely soluble in the matrix. Source
These reduced coenzymes store electron energy that originated in the carbon bonds of acetyl-CoA.
Energy yield per turn (per acetyl-CoA)
Products generated per cycle turn:
3 NADH
1 FADH₂
1 ATP (or GTP) via substrate-level phosphorylation
2 CO₂
Thus, per glucose (two acetyl-CoA entering):
6 NADH, 2 FADH₂, 2 ATP (or GTP), and 4 CO₂ are produced by the Krebs cycle.
Control points (conceptual regulation)
Krebs cycle flux responds to cellular energy status:
High ATP and high NADH tend to inhibit key oxidative steps (reduced need for further electron harvesting)
Availability of NAD⁺/FAD and oxaloacetate supports continued cycling and electron capture
FAQ
It commits pyruvate to acetyl-CoA formation, linking carbohydrate breakdown to mitochondrial oxidation.
It is strongly regulated by the balance of NADH/NAD$^+$ and acetyl-CoA/CoA, coordinating carbon entry with the cell’s capacity to oxidise it.
Usually not. In early turns, the CO$_2$ released typically comes from carbons that were already part of oxaloacetate.
The acetyl carbons become part of the regenerated oxaloacetate and are released as CO$_2$ in later turns.
Several intermediates can be diverted for biosynthesis (e.g., amino acid precursors), while the cycle simultaneously breaks down acetyl-CoA for energy capture.
Cells replenish intermediates to keep the cycle running when withdrawals occur.
It produces ATP (or GTP) directly from a high-energy intermediate without using an electron transport chain.
This provides a small but immediate ATP yield even when downstream electron processing is limited.
They use anaplerotic (“filling up”) reactions that convert other metabolites into Krebs intermediates.
A common route converts pyruvate into oxaloacetate, maintaining cycle capacity when intermediates are withdrawn for biosynthesis.
Practice Questions
State two products of pyruvate oxidation and describe what happens to NAD during this process. (3 marks)
CO produced (1)
Acetyl-CoA produced (1)
NAD is reduced to NADH (accepts electrons/hydrogen) (1)
Describe how the Krebs cycle both releases carbon dioxide and captures energy from acetyl-CoA. Include yields per turn. (6 marks)
Acetyl-CoA (2C) combines with oxaloacetate (4C) to form citrate (6C) (1)
Two decarboxylations occur, releasing 2 CO per turn (1)
NAD is reduced to NADH during oxidation steps (3 NADH per turn) (2; one for reduction idea, one for correct yield)
FAD is reduced to FADH (1 per turn) (1)
One ATP (or GTP) made by substrate-level phosphorylation (1)
