Ultrasensitivity in biochemical systems controlled by covalent modification. Interplay between zero-order and multistep effects

J Biol Chem. 1984 Dec 10;259(23):14441-7.


A previous analysis of covalent modification systems (Goldbeter, A., and Koshland, D. E., Jr. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 6840-6844) showed that steep transitions in the amount of modified protein can occur when the converter enzymes are saturated by their protein substrate. This "zero-order ultrasensitivity" can further be amplified when an effector acts at more than one step in a monocyclic or multicyclic cascade of covalent modification. We analyze the limitations of the latter "multistep ultrasensitivity" and show how it can combine with the zero-order effect to enhance the sensitivity of biochemical systems controlled by covalent modification.

Publication types

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

MeSH terms

  • Allosteric Regulation
  • Kinetics*
  • Mathematics
  • Models, Biological*
  • Protein Binding
  • Proteins / metabolism*


  • Proteins