L7 - Enzymes As Drug Targets Flashcards
What is the purpose of enzymes?
Act as powerful catalysts, increasing reaction rates up to 1,000,000-fold.
Do not change reaction equilibrium.
Highly specific, catalysing one chemical reaction and minimising by-products.
Lower activation energy by stabilising the transition state.
What is the transition state in enzymatic reactions?
A highly unstable, energetically unfavourable intermediate during a reaction.
How do enzymes lower activation energy?
Provide a reaction surface (active site) and hydrophobic environment.
Bring substrates together in the correct orientation.
Weaken substrate bonds.
Participate in reaction mechanisms (e.g., acid/base catalysis, nucleophilic groups).
What is the active site of an enzyme?
A small hydrophobic hollow or cleft on the enzyme surface.
Contains amino acids that bind and catalyse reactions.
Stabilises the transition state through precise fit and induced fit.
What are the models of enzyme-substrate binding?
Lock and Key (Emil Fischer, 1890): Active site matches the substrate exactly.
Induced Fit: Active site adjusts shape to fit substrate and strain bonds for easier reaction.
What are the main mechanisms of enzymatic catalysis?
Acid/base catalysis.
Nucleophilic residues (e.g., serine).
Transition state stabilisation (e.g., catalytic triads of serine, histidine, aspartate).
Use of cofactors (e.g., Zn²⁺, NAD⁺).
How do competitive inhibitors work?
Resemble the substrate and bind to the active site.
Can be reversible (e.g., methotrexate) or irreversible (e.g., fluorouracil).
Effects can be overcome by increasing substrate concentration.
What is the difference between uncompetitive and non-competitive inhibition?
Uncompetitive: Inhibitor binds only to the enzyme-substrate complex.
Non-competitive: Inhibitor binds to a site other than the active site, changing enzyme shape.
What is IC50, and how does it differ from EC50?
IC50: Inhibitor concentration that reduces enzyme activity by 50%.
EC50: Concentration of a drug that gives 50% of its maximal response, measuring potency.
What are allosteric modulators?
Molecules binding to allosteric sites, modifying enzyme activity at the orthosteric site.
Types: Positive (PAM), Negative (NAM), or Neutral/Silent.
What is Km in enzymology?
Michaelis constant: Substrate concentration that achieves half the maximal enzymatic reaction rate.
What are key concepts of enzymatic catalysis?
Enzymes lower activation energy.
Active site binding ensures specificity and induced fit.
Enzymes can actively participate in reaction mechanisms.
Competitive inhibitors mimic substrates at the active site.
