Enzyme Classification and Localization

Study Notes

Enzymes can be categorized based on their activity location.
- Intracellular enzymes: Function inside cells and are typically nonfunctional in plasma.
- Extracellular enzymes: Operate outside of cells and can be further classified:
  - Secretory enzymes: Functionally active in plasma.
  - Excretory enzymes: Nonfunctional in plasma.

Enzymes accelerate reactions by lowering the activation energy needed to reach the transition state.
They achieve this by stabilizing the transition state, thus decreasing the energy required to form products.
Enzyme specificity is crucial and can be categorized:
- Reaction specificity: Enzymes catalyze only a specific type of reaction.
- Substrate specificity: Enzymes bind and act only on specific substrates.

Lock and Key Model: Proposed by Emil Fischer in 1894, this model describes the enzyme and substrate as perfectly complementary shapes, like a lock and key, that fit together.
Induced Fit Model: Proposed by Daniel Koshland in 1958, this model suggests that the enzyme's active site is flexible and changes conformation when it binds to the substrate, leading to a better fit.

The active site is the region of the enzyme responsible for substrate binding and catalysis.
The enzyme hexokinase provides a classic example of induced conformational change. Its active site undergoes a shape change upon binding to glucose.

Substrate concentration: The rate of an enzyme-catalyzed reaction increases with substrate concentration, but there is a maximum rate that can be achieved.
Competitive inhibition: Inhibitor molecules compete with the substrate for binding to the active site, reducing reaction rate.
- Effects of competitive inhibition on kinetics: Michaelis-Menten constant (Km) increases, indicating decreased substrate affinity, while the maximum velocity (Vmax) remains unchanged.
Noncompetitive inhibition: Inhibitor molecules bind to a different site on the enzyme, altering its conformation and reducing its activity.
- Effects of noncompetitive inhibition on kinetics: Both Km and Vmax are affected. Km generally increases due to reduced substrate affinity, and Vmax decreases due to the inhibitor's effect on enzyme activity.

Zymogen activation: Some enzymes are synthesized as inactive precursors called zymogens. Activation occurs through proteolytic cleavage, removing a portion of the molecule and revealing the active site.
Covalent modifications: Enzymes' activity can be regulated by covalent modifications like phosphorylation, dephosphorylation, or acetylation. These changes can activate or deactivate the enzyme.