Chapter 8- Mechanisms/Inhibitors

Question 1

Strategies for forming the transition state

Answer 1

• Covalent Catalysis: active site contains a reactive group usually a powerful nucleophile that temporarily is covalently modified
• General Acid/Base: molecule other than water plays the role of proton donor or acceptor (ex: histidine residue)
• Metal ion: stabilizes a negative charge or increasing acidity of nearby molecule or by binding to the substrate
• approximation/orientation: bringing two substrates into proximity

Question 2

3 types of reversible inhibition

Answer 2

Competitive: inhibitor resembles the substrate and binds to the active site. Ex: ibuprofen, statins. Can be relieved by increasing substrate concentration. (Plot looks like chopsticks: think competitive Chinese)
Uncompetitive: inhibitor binds only to the SE complex. Ex: herbicide glyphosate in plants. Plot lines are parallel.
Noncompetitive: different binding site than substrate. Cannot be relieved by increasing substrate concentration.

Question 3

Irreversible Inhibitors

Answer 3

Tightly bound to enzyme
Ex: penicillin, aspirin

• modify functional groups
• this identification can map active sites