Enzyme Inhibition Flashcards
What is a reversible inhibitor?
An inhibitor that binds to the enzyme non-covalently.
What is a competitive inhibitor?
- resembles substrate structure- competes directly with substrate for active site- binds to the active site but is unreactive
What parameters are affected by competitive inhibition?
Km - affecting the affinity for substrate.Vmax is not affected by competitive inhibition.
What is an uncompetitive inhibitor?
- binds to an allosteric site on the ES complex - can cause distortion of the active site
What parameters are affected by uncompetitive inhibition?
Both Vmax and Km.
What is a mixed inhibitor?
- bind to an allosteric site - can bind to free enzyme or ES complex - effective inhibition at both low and high substrate concentrations
Which parameters are affected by mixed inhibition?
Both Vmax and Km.
What is a non-competitive inhibitor?
- binds at an allosteric site - effectiveness depends on inhibitor concentration
Which parameters are affected by non-competitive inhibition?
Vmax lowers as inhibitor concentration increases.Km is not affected as EI can still bind substrate.
What are the types of reversible inhibition?
Competitive, uncompetitive, mixed and non-competitive.
What are the types of irreversible inhibitors?
Group specific covalent modifying agents, affinity labels, suicide substrates and transition state analogues.
What are group-specific covalent modifying agents?
Inhibitors that react with specific types of enzyme functional groups, e.g. Ser-OH, Cys-SH and His-imidazole.
What is an example of a group-specific covalent modifying agent?
DIPF which reacts with specific Ser-OH in acetylcholinesterase at synapses, poisoning nerves.
What is an affinity label?
Have a similar structure to the substrate and react at the active site, covalently inactivating the enzyme.
Give an example of an affinity label.
TPCK - has a phenyl group which binds in the active site of chymotrypsin
What are suicide substrates?
Have a similar structure to the substrate and the enzyme treats them as a substrate, starting the catalytic reactions with the inhibitor. This leads to the inhibitor reacting covalently with the enzyme, making the enzyme inactive.
Give an example of a suicide substrate.
Penicillin- inhibits transpeptidase, preventing bacterial wall synthesis.
What is a transition state analogue?
Have a structure similar to the transition, binding more tightly to an enzyme than a substrate.
What are transition state analogues useful for?
-understanding catalytic mechanisms and the structure of the transition state which can not be isolated experimentally.-very specific inhibitors of enzymes in pharmaceuticals.-antigens for immunising lab animals to generate antibodies with binding sites complementary to the transition state.
Give an example of a transition state analogue.
Saquinavir is used to inhibit HIV protease in HIV treatment.
What is an irreversible inhibitor?
An inhibitor that reacts with the enzyme and changes it chemically.
How can competitive inhibition be overcome?
The inhibitor is displaced at high concentrations of substrate.
How can uncompetitive inhibition be overcome?
Lowering the concentration of the substrate makes the effect of the inhibitor negligible.
