7.2

Allosteric enzymes have multiple subunits and exhibit Quaternary structure, such as hemoglobin, which serves as a carrier protein. These enzymes are modulated by regulatory subunits that control the activity of catalytic subunits, which are separate proteins.

  1. Allosteric Modulation
       - Positive modulators (activators) like ATP bind to regulatory subunits, altering the shape of the catalytic pocket and increasing substrate affinity, thus promoting reaction rates. For example, ATP signaling increases enzyme activity.
       - Negative modulators (inhibitors) like CTP bind to regulatory subunits, reducing the catalytic subunit's affinity for its substrate. CTP is a product of the pathway and inhibits further reactions.
       

  2. Examples of Allosteric Regulation
       - Hemoglobin binds oxygen, which increases the affinity of its other subunits for oxygen, acting as a homotropic modulator.
       - CO2, H+, and 2,3-BPG are negative modulators for hemoglobin, reducing its activity.

  3. Mechanism of Action
       - Allosteric regulators bind to sites separate from the catalytic site, unlike competitive inhibitors, which can be overcome by increasing substrate concentration.
       

  4. Structural Characteristics
       - Allosteric proteins utilize a tense (T) state with low substrate affinity and a relaxed (R) state with high affinity. Most proteins are naturally in the tense state to prevent unnecessary activity.
       

  5. Kinetic Behavior
       - Allosteric enzymes demonstrate a sigmoidal curve on reaction velocity graphs, indicative of cooperative behavior among subunits. Increased cooperativity results in a more pronounced plateau, while decreased cooperativity results in a curve shape more akin to myoglobin    

  6. Kinetics Terminology
       - K0.5 is used instead of KM to describe the concentration of substrate at half Vmax for allosteric systems. Two types of inhibition systems:       - K-systems change K0.5 (KM) without affecting Vmax.
          - H-systems change Vmax without affecting K0.5.
           Review this information in conjunction with previous lectures on inhibition systems to solidify understanding of allosteric regulation and its implications for enzyme kinetics.