Enzyme- Targeted Drugs Flashcards
1
Q
Reversible inhibition
A
- competitive inhibitor
- competes with natural substrate
- does not undergo reaction
- drug binds and releases
- the longer the inhibitor binds the active site, the more potent the inhibitor
- changes can be made to the binding strength of the inhibitor strength of the inhibitor to yield drugs with different inhibitor strengths
2
Q
Irreversible inhibition
A
- non-competitive
- binds irreversible to active site
- typically the drug contains an electrophile that forms a covalent bond upon binding to active site
- Nucleophilic amino acids containing OH and SH groups react with electrophile
- clogs up active site
- enzyme becomes useless after binding
3
Q
Allosteric inhibition
A
- As long as downstream product is bound, the active site is not active
- adding more substrate will not effect kinetics
- reversible
- conformational change, so substrate no longer fits
- substrate binds to active site
- inhibitor binds to allosteric site
- considered noncompetitive, because it is not binding to active site
- all equilibrium
4
Q
What defines a catalytic process?
A
not used up in reaction
5
Q
Vmax
A
the maximum velocity (rate) at which a given amount of enzyme will convert to substrates to products
6
Q
Km
A
amount of substrate required to reach half Vmax
7
Q
Kcat
A
number of substrates handled by one active site per second
8
Q
Michael’s Menten equation
A
V = Vmax [S]/Km+[S]
9
Q
Competitive inhibitor vmax and Km
A
same Vmax different Km (shifted right)
10
Q
Noncompetitive inhibitor Vmax and Km
A
different Km (lower) same Km
11
Q
Receptors function
A
- responsible for signal transduction
- upon binding, undergo conformational change that activates signaling pathway
- depending on disease, receptor targeted drugs seek to inhibit or increase signaling
12
Q
Receptor agonists
A
- upon binding, agonists produce conformation change in the receptor needed for activation
- often in drug synthesis, the structure of known ligands for receptors are the starting point
13
Q
Why would you design an agonist for a receptor target?
A
up regulate
EX: insulin, opioids
14
Q
Receptor antagonists
A
- upon binding the receptor does not undergo shape change
- if the antagonist works, but can’t fit into binding pocket (allosteric antagonist, umbrella effect)
15
Q
Receptor partial agonists
A
- many drugs have been found to not be pure agonists or antagonists
- reason is because receptor can undergo shape change, but not very efficiently
- dual agonists and antagonist character
