lecture 2/18

Enzymes are exceptional catalysts that significantly speed up biochemical reactions.
The range of catalytic efficiency can vary widely, from 10^5 to 10^17 times faster than uncatalyzed reactions.

Enzymes facilitate reactions by rearranging covalent bonds within the substrate, leading to faster chemical processes.
Example discussed: Isomerase enzyme moves phosphate groups within a molecule.

Rearrangement of Covalent Bonds
- Enzymes use their structure to stabilize the transition state of a reaction.
- As substrates bind to the enzyme’s active site, they form new covalent bonds, thereby lowering activation energy required for the reaction.
- Example: A substrate fits into the catalytic site (analogy of "Pacman") where covalent bonds are manipulated.
Noncovalent Interactions
- Enzymes also utilize noncovalent interactions like hydrogen bonds and ionic interactions in the catalytic process, which contribute to lowering activation energy further.
- Upon binding, energy is released, referred to as binding energy, which plays a crucial role in decreasing the activation energy.

Binding energy is fundamental to the enzyme mechanism—it's the energy captured from interactions that facilitates the reaction to progress.
Change in Gibbs free energy (ΔG) occurs upon substrate binding, indicating a stable interaction.

Proposed by Emil Fischer in 1894, suggesting enzymes possess a rigid structure fitting a specific substrate (lock and key).
Criticism: The model is too simplistic because enzymes are dynamic and can change conformation.

Enzymes are not static; they undergo conformational changes upon substrate binding, allowing flexibility (like bending a rod).
This model effectively explains how enzymes can stabilize the transition state of reactions.

To occur, reactions require specific orientations and energy. Enzymes enhance the likelihood of substrates coming together in the desired orientation.
The experimentation shows that constraints imposed by enzymes significantly enhance reaction rates (e.g., tethered interactions leading to increased reaction speed).

Catalytic sites are dynamic; they must adjust to facilitate binding and catalysis. Movement within these sites is essential for optimal function.
Importance of enzyme flexibility is highlighted, as constrained molecules react faster than unrestricted counterparts.

Enzymes may form temporary covalent bonds with substrates during the catalytic cycle.
Metal ions and cofactors play a significant role in the enzymatic mechanism, aiding in substrate processing.

Aspirin functions as an inhibitor blocking enzyme activity in prostaglandin biosynthesis, demonstrating the balance between enzyme function and regulation.

Understanding the mechanisms of enzymatic action—including covalent and noncovalent interactions—is crucial for appreciating their role in biochemical reactions.