Krebs Cycle

This lesson covers: 

  1. Where the Krebs cycle occurs
  2. The main steps of the Krebs cycle
  3. The role of coenzymes like NAD and FAD
  4. The importance of the Krebs cycle

Introduction to the Krebs cycle

The Krebs cycle, also known as the citric acid cycle, is a stage of aerobic respiration that follows glycolysis and the link reaction. It takes place in the mitochondrial matrix.


It processes acetyl CoA to prepare substrates for the final stage of aerobic respiration (oxidative phosphorylation).


For each molecule of acetyl CoA, the Krebs cycle produces:

  • Two molecules of carbon dioxide as a by-product.
  • Electron carriers, including three molecules of reduced NAD and one molecule of reduced FAD, which are needed for oxidative phosphorylation.
  • One molecule of ATP through substrate-level phosphorylation.

The main steps of the Krebs cycle

Diagram showing the main steps of the Krebs cycle including the formation of citrate, decarboxylation, dehydrogenation, and ATP synthesis.

The Krebs cycle involves a sequence of enzymatic reactions:

  1. The two-carbon (2C) acetyl CoA merges with a 4C molecule, oxaloacetate, to create a 6C molecule, citrate.
  2. Citrate is decarboxylated, releasing two molecules of carbon dioxide.
  3. Citrate is also dehydrogenated (oxidised), releasing hydrogens that reduce three molecules of NAD and one molecule of FAD.
  4. For each acetyl CoA that enters the cycle, one ATP (or GTP in some organisms) is synthesised directly via substrate-level phosphorylation.
  5. Oxaloacetate is regenerated for the next turn of the cycle.

The role of coenzymes

Coenzymes such as NAD and FAD, along with coenzyme A, play essential roles in the Krebs cycle.


Initially, they act as oxidising agents, accepting electrons and protons and becoming reduced themselves. These reduced coenzymes later donate these gained electrons to the electron transport chain, facilitating the transfer of electrons that is crucial for the synthesis of ATP.


Differences between NAD and FAD:

  • NAD accepts one electron and one proton when it is reduced, FAD accepts two protons and two electrons when it is reduced.
  • NAD participates in all stages of respiration, while FAD only accepts protons and electrons in the Krebs cycle.
  • NAD results in the synthesis of three ATP molecules, while FAD results in the synthesis of two ATP molecules.

Importance of the Krebs cycle

The Krebs cycle is essential for several reasons:

  • It oxidises and breaks down large nutrients into smaller ones, like carbon dioxide, which can be removed as a waste product.
  • It generates reduced NAD and reduced FAD, which carry protons and electrons into oxidative phosphorylation.
  • It continually regenerates the 4C molecule to combine with acetyl CoA molecules.
  • It provides a variety of intermediate compounds required for the biosynthesis of essential cellular components such as fatty acids, amino acids, and chlorophyll.