Lecture 7

Question 1

What’s the first step in catalysis?

Answer 1

Formation of enzyme-substrate complex.

Question 2

How do enzymes work as catalysts?

Answer 2

Bring substrates together in favourable orientations to promote formation of the transition state.

Question 3

What is Pauling’s hypothesis?

Answer 3

Transition state binds more strongly to the enzyme than the substrate.

Question 4

What are transition state analogues?

Answer 4

Molecules similar in structure to the transition state.

Question 5

What are 2 examples of transition state analogues?

Answer 5

Yeast aldolase, Adenosine deaminase.

Question 6

Who was the lock and key hypothesis coined by, and when?

Answer 6

Emil Fischer, 1890.

Question 7

Who was the induced fit hypothesis coined by, and when?

Answer 7

Daniel Koshland, 1958.

Question 8

How do substrates bind to the active site?

Answer 8

By multiple weak interactions.

Question 9

Why does Mitogen-activated protein kinase ERK2 use phosphate, and where from?

Answer 9

Uses phosphate from ATP to phosphorylate proteins.

Question 10

What does the active site contain?

Answer 10

Amino acids involved in catalysis.

Question 11

What 3 features does Mitogen-activated protein kinase ERK2 have?

Answer 11

ATP binding site, Substrate binding site (proteins), catalytic loop.

Question 12

What are the 3 parts of Tetrahydrofolate reductase’s active site?

Answer 12

Catalytic site, 
Hydrophobic region (substrate binding)
Polar region (substrate binding).

Question 13

What is important in substrate binding?

Answer 13

Proximity and orientation favour formation of TS.

Strong binding of TS lowers DG‡

Question 14

What is the entropy effect?

Answer 14

Substrates held next to each other or catalytic groups for an increased length of time.

Question 15

What is orbital steering?

Answer 15

Best orientation of substrate relative to catalytic groups.

Question 16

How does maximal binding occur in the induced fit hypothesis?

Answer 16

Changes to conformation of E and S.

• specificity.
• promotes formation of transition state.

Question 17

Why is the open conformation of hexokinase beneficial enzymatically?

Answer 17

It enables substrate binding.

Question 18

What does the closed conformation enable for hexokinase?

Answer 18

The reconstitution of the catalytic site - means it’s only active when bound to substrate.

and excludes water.

Question 19

What are co-factors?

Answer 19

A required non-proteinous component for some enzymes.

Question 20

What’s the name for an inactive protein without its cofactor?

Answer 20

Apoenzyme.

Question 21

What’s the name for an active protein with it cofactor?

Answer 21

Holoenzyme.

Question 22

What are the 2 types of molecules that can act as cofactors?

Answer 22

Organic = coenzyme.

Metal ion.

Question 23

What is a coenzyme?

Answer 23

An organic cofactor.

Question 24

What is a prosthetic group?

Answer 24

Cofactor that binds irreversibly to the enzyme.

Question 25

Do cofactors extend the range of chemical reactions enzymes can catalyse?

Answer 25

Yes.

Question 26

4 functions of metal ions?

Answer 26

Substrate binding, Orientation, Electrophile in acid-base catalysis - stabilises negative charge. Redox reactions (amino acids not suited to).

Question 27

What is the name for a strongly bound metal ion to an enzyme?

Answer 27

Metalloenzyme.

Question 28

What is the name for a weakly bound metal ion to an enzyme?

Answer 28

Metal-activated enzyme.

Question 29

3 mechanisms of catalysis?

Answer 29

Covalent catalysis, General acid-base catalysis, Metal ion catalysis.

Question 30

What does the active site contain specifically in covalent catalysis, and what happens to it?

Answer 30

A reactive group (usually nucleophile), that's covalently modified during the reaction.

Question 31

What amino acids are commonly involved in covalent catalysis?

Answer 31

Serine, cysteine, histidine, lysine.

Question 32

When does general acid-base catalysis occur?

Answer 32

When a molecule other than water acts as proton donor or acceptor.

Question 33

What do proton donors or acceptors do in acid-base catalysis? How does this benefit some reactions?

Answer 33

Stabilise intermediates by transferring charges to or from those intermediates. Reduces likelihood of intermediates reverting back to substrates (more likely for some reactions).

Question 34

Generally, what are the 3 ways enzymes can increase reaction rates?

Answer 34

Holding substrates together - entropy/orbital steering. Promote formation of transition state - induced fit. Contribute reactive groups - AA side chains, cofactors.