17: Inhibitor Kinetics (cont.), Sigmoidal kinetics, Enzyme Activation
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Reading & Problems: LNC p. 210-213
I. Other effects on enzyme activity.
increase in temperature speeds reaction, but high temperature will reduce enzyme stability. Most enzymes have a temperature optimum.
can change state of catalytic groups or substrates accelerating or decelerating reaction. Usually a pH optimum that is characteristic of each enzyme.
C. Reversible covalent modification
phosphorylation most common. Occurs on specific Ser, Thr or Tyr residues. Can activate or inactivate depending on the particular enzyme. Addition of phosphate catalyzed by specific protein kinase (using ATP as donor), removal by specific protein phosphatase which releases free phosphate.
D. Proteolytic activation
enzyme synthesized as a pre-enzyme called "zymogen" that is cleaved by a protease to produce the active enzyme.
- Trypsin and chymotrypsin are produced this way and the zymogen precursors of these are called "trypsinogen" and "chymotrypsinogen".
- The formation of blood clots is activated by a series of proteolytic activation events that finally result in conversion of fibrinogen to fibrin and the formation of large fibrin polymers as the main components of the blood clots.
G&GIV Fig. 15.4 Every protein in the pathway, excepting the last protein, fibrinogen/fibrin, is a protease that cleaves and activates the next protein in the progressive activation pathway.
III. Solving enzyme kinetic problems - a few examples
Some take home information:
|Inhibitor||Binds to||Constant changed|
|Noncompetitive||ES, E||Vmax lower|
|Uncompetitive||ES||Vmax lower, Km lower|
If constant is Higher -> multiple by "the inhibitor factor" = 1+([I]/KI)
If constant is Lower -> divide by "the inhibitor factor" = 1+([I]/KI)
Charles S. Gasser (Department of Molecular & Cellular Biology; UC Davis)