Enzymes As Drug Targets Flashcards
What are enzymes?
Enzymes are protein molecules that catalyze specific reactions without being consumed in the process.
Why are enzymes important in biochemical reactions?
They accelerate reactions in biochemical systems, making life-sustaining processes possible at 37°C in the human body.
What is the active site of an enzyme?
The active site is the region where substrate binding and catalysis occur, involving non-covalent interactions.
What are the two models of enzyme-substrate binding?
The Lock and Key model (exact fit) and the Induced Fit model (flexible fit).
How do enzymes lower activation energy?
By providing an alternative reaction pathway with a lower Gibbs activation energy.
What are the two steps in enzyme-catalyzed reactions?
Step 1: Reversible binding of substrate to enzyme. Step 2: Irreversible conversion to product.
What is the Michaelis-Menten equation?
v = (Vmax [S]) / (Km + [S]), describing the rate of enzyme-catalyzed reactions.
What is Vmax?
The maximum reaction rate when an enzyme is fully saturated with substrate.
What is Km (Michaelis constant)?
The substrate concentration at which reaction velocity is half of Vmax, indicating substrate affinity.
What does a high Km indicate?
A weak substrate binding, requiring higher substrate concentration to reach Vmax.
What does a low Km indicate?
Strong substrate binding, achieving Vmax at lower substrate concentrations.
What is the turnover number of an enzyme?
The number of substrate molecules converted to product per enzyme molecule per second when saturated.
How are enzymes used as drug targets?
Many drugs inhibit enzymes to alter metabolic pathways associated with diseases.
What are irreversible enzyme inhibitors?
Inhibitors that covalently bind or form a highly stable association, permanently inactivating the enzyme.
Give an example of an irreversible enzyme inhibitor.
Penicillins, which inhibit bacterial transpeptidase enzymes, disrupting cell wall synthesis.
What are reversible enzyme inhibitors?
Inhibitors that bind non-covalently and can be removed, allowing enzyme activity to be restored.
What are the three types of reversible inhibitors?
Competitive, uncompetitive, and mixed inhibitors.
What is competitive inhibition?
The inhibitor competes with the substrate for the active site, increasing Km but not affecting Vmax.
What is uncompetitive inhibition?
The inhibitor binds only to the enzyme-substrate complex, decreasing both Km and Vmax.
What is mixed inhibition?
The inhibitor binds both to the enzyme and enzyme-substrate complex, decreasing Vmax and affecting Km variably.
What is non-competitive inhibition?
A special case of mixed inhibition where the inhibitor decreases Vmax but does not affect Km.
What is an example of a targeted irreversible enzyme inhibitor?
EGFR inhibitors in cancer therapy, which covalently modify a cysteine residue in the enzyme.
What are suicide inhibitors?
Irreversible inhibitors that initially bind reversibly but then form a covalent bond, permanently inactivating the enzyme.
Why is enzyme specificity important in drug design?
High specificity reduces side effects and increases therapeutic efficacy.
How can enzyme inhibition strength be measured?
Using Ki (inhibitor dissociation constant), where lower Ki indicates stronger binding.
