Week 7: Applications of Binding, Kinetics, and Catalysis

Lectures 13&14: Mixed enzyme inhibition, multisite phosphorylation, and ultrasensitivity

Outline

  1. Mixed inhibition
    1. General derivation
    2. Limiting cases: "competitive," "uncompetitive," and "noncompetitive"
  2. Reversible phosphorylation ("Push-pull" systems)
    1. Single site
    2. Multisite
    3. Zeroth order ultrasensitivity
    4. Ultrasensitivity through bistability

Reading

  • (optional) A. Goldbeter and D. E. Koshland, Jr., “An amplified sensitivity arising from covalent modification in biological systems,” Proc. Natl. Acad. Sci. USA, vol. 78, no. 11, pp. 6840–6844, 1981. (pdf)
  • (optional) J. E. Lisman, “A mechanism for memory storage insensitive to molecular turnover: a bistable autophosphorylating kinase.,” Proc. Natl. Acad. Sci. U. S. A., vol. 82, no. 9, pp. 3055–7, May 1985. (pdf)

Notes

  • Mixed inhibition through zeroth order ultrasensitivity (pdf)
  • Bistability in autophosphorylation (pdf)