lec 18 full notes

Lecture Topic: Enzyme Regulation
Instructor: Dr. Setty
Important Terms: HCI Acid, Pepsin, Competitive Inhibition, Allosteric Regulation, Covalent Modification, Zymogen Activation, Feedback Inhibition

Definition: A compound binds to the active site of an enzyme, preventing the substrate from binding.
Commonly involved substances: Toxins and drugs.
Key Point: It is usually a reversible mechanism.

Definition: A molecule binds to an enzyme at a site other than the active site, inducing a conformational change that affects the activity of the enzyme.
- Can be either activating or inhibitory.
- Always reversible as it occurs naturally.
Terminology: "Allo-" means other, and "-steric" refers to shape.

Mechanism: The activator binds somewhere other than the active site, resulting in an active site that can bind substrates.
Result: Increased reaction rates.
Equilibrium: Active and inactive forms of the enzyme are in equilibrium, with allosteric activators favoring the active form.

Mechanism: The inhibitor binds to a site other than the active site, locking the enzyme in its inactive form.
Result: Decreased reaction rates.
Equilibrium: Similar to activation, where equilibrium exists between active and inactive forms, but the inhibitor stabilizes the inactive form.

Usually occurs in response to a cellular stimulus.
Definition: Commonly involves phosphorylation, which is reversible via dephosphorylation by a phosphatase.
Activation/Inactivation: It can either activate or inactivate enzymes depending on the nature of the modification.
Example: Glycogen synthase is inhibited by phosphorylation and functions only when dephosphorylated.

Definition: A zymogen is an inactive precursor of an enzyme.
Mechanism: The zymogen is cleaved to produce an active enzyme, which mitigates the risk of premature activation that could damage cells.
Example: Pepsinogen is processed into pepsin in the acidic environment of the stomach (low pH), exposing the active site by removing a masking sequence.

Many pancreatic digestive enzymes are initially zymogens.
Process: Digestive zymogens released into the duodenum are activated by enterokinase, which converts trypsinogen to trypsin. Then trypsin activates additional digestive enzymes.

Purpose: To maintain homeostasis in the cell.
- Ensures sufficient production of compounds without excess.
- Prevents depletion of reactants that are needed for other metabolic pathways.
- Avoid accumulation of toxic intermediates.

Definition: The product of a reaction binds to and inhibits the enzyme responsible for its own synthesis.
Characteristics:
- The cell regulates the amount of product produced.
- Protects substrate availability for other processes.
- Often resembles a competitive inhibition scenario.

Mechanism: The end product of a metabolic pathway inhibits the first enzyme in that pathway, effectively regulating the entire process typically through allosteric interactions.
Benefits:
- Ensures only necessary amounts of product are synthesized.
- Preserves reactants for potential use in other pathways.
- Prevents toxic intermediate build-up.
Example: In isoleucine biosynthesis, threonine is converted through multiple steps, ultimately being inhibited by isoleucine at the first enzymatic reaction to regulate pathway flow.

Feedback inhibition involves the inhibition of an enzyme by the product of the reaction it catalyzes or by a reaction earlier in the pathway.
Main Points:
- Prevents excess product synthesis.
- Protects substrates from depletion when needed elsewhere.
- Reduces the risk of toxic intermediate accumulation.
- Feedback generally occurs through direct inhibition or end-product inhibition, which is normally an allosteric process.

Mechanisms:
- Competitive Inhibition: Direct binding to active site.
- Allosteric Regulation: Binding to non-active sites.
- Covalent Modification: Usually phosphorylation which can activate or inactivate.
- Zymogen Activation: Mechanism for enzyme storage and activation at the appropriate times (e.g., Pepsinogen to Pepsin).
Feedback Inhibition Principles: Direct inhibition vs. End-product inhibition, typically involving allosteric regulation.