The biological significance of substrate inhibition: a mechanism with diverse functions

Bioessays. 2010 May;32(5):422-9. doi: 10.1002/bies.200900167.


Many enzymes are inhibited by their own substrates, leading to velocity curves that rise to a maximum and then descend as the substrate concentration increases. Substrate inhibition is often regarded as a biochemical oddity and experimental annoyance. We show, using several case studies, that substrate inhibition often has important biological functions. In each case we discuss, the biological significance is different. Substrate inhibition of tyrosine hydroxylase results in a steady synthesis of dopamine despite large fluctuations in tyrosine due to meals. Substrate inhibition of acetylcholinesterase enhances the neural signal and allows rapid signal termination. Substrate inhibition of phosphofructokinase ensures that resources are not devoted to manufacturing ATP when it is plentiful. In folate metabolism, substrate inhibition maintains reactions rates in the face of substantial folate deprivation. Substrate inhibition of DNA methyltransferase serves to faithfully copy DNA methylation patterns when cells divide while preventing de novo methylation of methyl-free promoter regions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • DNA Modification Methylases / metabolism
  • Enzymes / metabolism*
  • Folic Acid / metabolism
  • Gene Expression Regulation
  • Humans
  • Kinetics
  • Phosphofructokinases / metabolism
  • Substrate Specificity
  • Tyrosine 3-Monooxygenase / metabolism


  • Enzymes
  • Folic Acid
  • Tyrosine 3-Monooxygenase
  • DNA Modification Methylases
  • Phosphofructokinases
  • Acetylcholinesterase