Biochemistry · Enzymes & Bioenergetics

Phosphofructokinase-1 (PFK-1), the key regulatory enzyme of glycolysis, displays sigmoidal kinetics with respect to its substrate fructose-6-phosphate. High concentrations of ATP allosterically inhibit PFK-1 by decreasing its affinity for the substrate. This regulatory behavior is best explained by which model of enzyme cooperativity?

  • A The concerted (MWC) model, where all subunits shift simultaneously between T and R states
  • B The induced-fit model, where substrate binding changes enzyme shape
  • C The lock-and-key model, where enzyme shape is rigid and pre-formed
  • D The sequential (KNF) model, where only the subunit that binds substrate undergoes conformational change
Correct answer: A. The concerted (MWC) model, where all subunits shift simultaneously between T and R states

Explanation

PFK-1 is a tetrameric allosteric enzyme exhibiting cooperative substrate binding and sigmoidal kinetics, best explained by the Monod-Wyman-Changeux (concerted) model. In this model, all subunits exist in either a tense (T, low affinity) or relaxed (R, high affinity) state and switch simultaneously. ATP stabilizes the T state (inhibition), whereas AMP and fructose-2,6-bisphosphate stabilize the R state (activation).

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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