Enzymes 3

Question 1

Instead of regulating all enzymes, what is controlled instead?

Answer 1

Many processes organised into pathways

–> regulate 1st step to control the total product from pathway

Question 2

What are the short + long term controls?

Answer 2

Short = controlling enzyme activity

Long = controlling making of enzyme via transcription

Question 3

What is feedback activated by in glycolysis?

Answer 3

Low energy signals = ADP + AMP

Question 4

What is feedback inhibited by in glycolysis?

Answer 4

High energy signals = ATP

Build up of intermediates
= citrate + acetylCoA

Question 5

What are the 3 types of enzyme inhibition?

Answer 5

Competitive
Non-competitive
Irreversible

Question 6

In competitive inhibition, how can the inhibitor be outcompeted?

Answer 6

Increasing substrate conc
(for a fixed competitor conc)
= increases rate of reaction

Question 7

Give an example of a competitive inhibitor

Answer 7

Dihydrofolate reductase used in nucleotide biosynthesis

= Inhibited by Methotrexate

Question 8

What is irreversible inhibition?

Answer 8

Mimics the substrate

• -> reacts with active site
• -> stops enzyme working indefinitely

Question 9

What are the 3 types of irreversible inhibitors?

Answer 9

> group-specific covalent modifying agents
transition state analogs
suicide inhibitors

Question 10

How do group-specific covalent modifying agents work?

Answer 10

React w/ specific type of enzyme functional group on ANY enzyme

Question 11

What do transition state analogs do?

Answer 11

Structurally similar to transition state

Bind even more tightly to enzyme than substrate binds
–> so v high affinity for active site

Question 12

What are transition state analogs useful for?

Answer 12

> Understanding catalytic mechanisms
V specific inhibitors of enzymes = pharmaceutical
antigens for immunising lab animals to generate antibodies w/ binding sites complementary to transition state

Question 13

How do suicide substrates work?

Answer 13

Similar structure to substrate
= binds to active site
–> enzyme reacts covalently (irreversibly) w/ inhibitor

Question 14

What does mechanism-based inhibition depend on?

Answer 14

Chemical mechanism of catalysis

Question 15

Give an example of a suicide substrate

Answer 15

Aspirin (acetylsalicylate)

Question 16

What do non-competitive inhibitors do?

Answer 16

Change enzyme’s affinity for substrate

= more difficult to bind

Question 17

What effect does increasing substrate conc have on a non-competitive inhibitor reaction?

Answer 17

Doesn’t increase rate of reaction

if regulator conc is constant

Question 18

Where in a pathway are non-competitive inhibitors normally found?

Answer 18

End product of a pathway

• -> tells regulated step enough product has been made
• -> negative feedback inhibition regulated step

Question 19

What is allosteric regulation?

Answer 19

Regulation of an enzyme by binding an effector molecule at a site other than active site
–> changes protein conformation

Question 20

In allosteric the effector must be, what … to the substrate?

Answer 20

Structurally unrelated

Question 21

How is allosteric inhibition much more sensitive than simple inhibition?

Answer 21

Relatively small amounts of effector needed

Produces relatively large effects

Question 22

What are the 2 types of covalent modification?

Answer 22

Reversible
= enzyme may exist in enzymatically inter-convertible form

Irreversible
= enzyme may be activated by cleavage

Question 23

What are the examples of reversible covalent modification?

Answer 23

Phosphorylation using ATP (via kinase) = inactivated
Phosphatase enzyme = reactivates

Adenylation using ATP (via adenyl transferase)
= inactivated
Removing AMP (via adenyl transferase)
= activated

Question 24

How are enzymes that are potentially harmful synthesised?

Answer 24

As inactive precursors in 1 enviro

–> transferred to another enviro where needs activating

Question 25

What is a zymogen?

Answer 25

an inactive substance converted into an enzyme + small peptide when activated by a protease

Question 26

Give an example of a zymogen

How is it formed?

Answer 26

Trypsin
= digestive enzyme that attacks protein

Trypsinogen –> trypsin + hexapeptide
(via action of enterokinase in stomach)

Question 27

What is premature trypsin normally inhibited by?

Answer 27

A suicide inhibitor