inhibitors and drug targets Flashcards
what is a reversible inhibitor?
Reversible inhibition occurs when a drug binds to the enzyme but can be displaced by increasing natural substrate concentration, allowing the enzyme’s function to resume
What are the key characteristics of irreversible inhibitors?
Irreversible inhibitors bind permanently to the active site, often forming covalent bonds with amino acids like serine or cysteine, leading to long-term enzyme inactivation
Why might reversible inhibition be preferred over irreversible inhibition?
Reversible inhibition avoids the toxic side effects associated with the permanent binding of irreversible inhibitors, which can react with other biological molecules.
What happens when a control agent binds to an allosteric site on an enzyme?
It induces a conformational change that blocks substrate access to the active site, regulating enzyme activity.
What is uncompetitive inhibition?
Uncompetitive inhibitors bind reversibly to the enzyme-substrate complex and are dependent on the substrate being present; increasing substrate concentration does not affect inhibition.
How does non-competitive inhibition work?
Non-competitive inhibitors bind to an allosteric site without affecting substrate binding but alter the enzyme’s activity, as seen in the drug Nevirapine for HIV-1.
What is a transition state analogue?
It is an inhibitor that mimics the high-energy transition state of a reaction, binding more strongly to the enzyme than the natural substrate or product to inhibit activity effectively.
What are suicide substrates?
These are drugs that are inactive until converted by the enzyme’s active site into a highly reactive species, which then binds irreversibly to the enzyme.
Give an example of an unwanted effect of a suicide substrate.
The diuretic drug tienilic acid was withdrawn due to toxicity caused by unintended suicide substrate action on cytochrome P450.
What mechanism is used by renin inhibitors to act as antihypertensive agents?
Renin inhibitors mimic the tetrahedral transition state of the hydrolysis reaction, effectively inhibiting renin and reducing blood pressure.
What role do allosteric sites play in feedback control mechanisms?
Binding of a final product to an allosteric site on the first enzyme of a biosynthetic pathway regulates enzyme activity, preventing overproduction.
