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First exams 2025

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The Link Reaction & The Krebs Cycle (HL) (HL IB Biology)

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Marlene

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Marlene

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The Link Reaction

Entering the link reaction

  • The end product of glycolysis is pyruvate (3C)
  • Pyruvate contains a substantial amount of chemical energy that can be further utilised in respiration to produce more ATP
  • When oxygen is available pyruvate will enter the mitochondrial matrix and aerobic respiration will continue
  • Once in the matrix pyruvate takes part in the link reaction

The link reaction

  • The link reaction takes place in the matrix of the mitochondria
  • It is referred to as the link reaction because it links glycolysis to the Krebs cycle
  • The steps are:
    • Oxidative decarboxylation reaction in which:
      • Carbon dioxide is removed to produce a 2C molecule 
      • This 2C molecule is then oxidised (loss of hydrogen and 2 high energy electrons) to produce an acetyl compound and thereby reducing NAD to NADH
    • Combination of the acetyl compound with coenzyme A to form acetyl coenzyme A (acetyl CoA)
  • It produces:
    • Acetyl CoA
    • Carbon dioxide (CO2)
    • Reduced NAD (NADH)

pyruvate + NAD + CoA → acetyl CoA + carbon dioxide + reduced NAD

  • Acetyl coenzyme A is supplied to the Krebs cycle where aerobic respiration continues 

Link Reaction Diagram

Link Reaction, downloadable AS & A Level Biology revision notes

The link reaction occurs in the mitochondrial matrix. It dehydrogenates and decarboxylates the three-carbon pyruvate to produce the two-carbon acetyl CoA that can enter the Krebs Cycle.

Examiner Tip

Remember that there are two pyruvate molecules produced per glucose molecule so you need to multiply everything by 2 when thinking about what happens to a single glucose molecule in aerobic respiration.

The Krebs Cycle

  • The Krebs cycle (sometimes called the citric acid cycle) consists of a series of enzyme-controlled reactions
  • The Krebs cycle takes place in the matrix of the mitochondria
  • Two carbon (2C) Acetyl CoA enters the circular pathway from the link reaction
  • A four carbon compound (4C) called oxaloacetate accepts the 2C acetyl fragment from acetyl CoA to form a six carbon compound (6C) called citrate
    • Coenzyme A is released in this reaction to be reused in the link reaction 
  • Citrate (6C) is then converted back to oxaloacetate (4C) through a series of oxidation-reduction (redox) reactions

The Krebs Cycle Diagram

the-krebs-cycle

The Krebs Cycle uses acetyl CoA from the link reaction to produce reduced carbon dioxide, reduced NAD, reduced FAD and ATP

The reactions involved in the Krebs cycle

  • Oxaloacetate (4C) is regenerated in the Krebs cycle through a series of redox reactions
  • Decarboxylation of citrate (6C)
    • Releasing two CO2 as waste gas
  • Oxidation (dehydrogenation) of citrate (6C) releases hydrogen atoms
  • Reduction of coenzymes NAD and FAD (by the released H atoms)
    • 3 NAD+ and 1 FAD → 3NADH + H+ and 1 FADH2
  • Substrate-level phosphorylation
    • A phosphate is transferred from one of the intermediates to ADP, forming one ATP
  • As the link reaction produces two molecules of acetyl CoA (one per each pyruvate), the Krebs cycle occurs twice
  • Per glucose molecule, the Krebs cycle produces:  
    • 4 CO2 
    • 2 ATP
    • 6 NADH + H+ (reduced NAD)
    • 2 FADH2 (reduced FAD)

Examiner Tip

The Krebs cycle is often referred to as cyclical or circular. This is because the 4C oxaloacetate is regenerated throughout the reaction so that it can start all over again by adding another acetyl CoA. 

You are required to name only the intermediates citrate (6C) and oxaloacetate (4C) in the Krebs cycle.

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Marlene

Author: Marlene

Expertise: Biology

Marlene graduated from Stellenbosch University, South Africa, in 2002 with a degree in Biodiversity and Ecology. After completing a PGCE (Postgraduate certificate in education) in 2003 she taught high school Biology for over 10 years at various schools across South Africa before returning to Stellenbosch University in 2014 to obtain an Honours degree in Biological Sciences. With over 16 years of teaching experience, of which the past 3 years were spent teaching IGCSE and A level Biology, Marlene is passionate about Biology and making it more approachable to her students.