Feedback Inhibition

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Understanding:

•  Metabolic pathways can be controlled by end-product inhibition

    
End-product inhibition (or feedback inhibition) is a form of negative feedback by which metabolic pathways can be controlled

  • In end-product inhibition, the final product in a series of reactions inhibits an enzyme from an earlier step in the sequence
  • The product binds to an allosteric site and temporarily inactivates the enzyme (via non-competitive inhibition)
  • As the enzyme can no longer function, the reaction sequence is halted and the rate of product formation is decreased


End-product inhibition functions to ensure levels of an essential product are always tightly regulated

  • If product levels build up, the product inhibits the reaction pathway and hence decreases the rate of further product formation
  • If product levels drop, the reaction pathway will proceed unhindered and the rate of product formation will increase


End-Product Inhibition

feedback inhibition

 

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Application:

•  End-product inhibition of the pathway that converts threonine to isoleucine

    
Isoleucine is an essential amino acid, meaning it is not synthesised by the body in humans (and hence must be ingested)

  • Food sources rich in isoleucine include eggs, seaweed, fish, cheese, chicken and lamb


In plants and bacteria, isoleucine may be synthesised from threonine in a five-step reaction pathway

  • In the first step of this process, threonine is converted into an intermediate compound by an enzyme (threonine deaminase)
  • Isoleucine can bind to an allosteric site on this enzyme and function as a non-competitive inhibitor


As excess production of isoleucine inhibits further synthesis, it functions as an example of end-product inhibition

  • This feedback inhibition ensures that isoleucine production does not cannibalise available stocks of threonine


Threonine  Isoleucine Pathway

isoleucine production