lecture 10 - enzyme catalysis

Question 1

Where does enzyme-substrate binding occur?

Answer 1

The active site

Question 2

What is the structure of an active site?

Answer 2

Has several amino acid side chains projecting into it that create binding specificity

Question 3

How does the active site bind substrate?

Answer 3

Via several weak interactions with amino acid residues

Question 4

What is the equation for the reaction of substrate and enzyme?

Answer 4

E + S ⇌ ES ⇌ EX‡ → EP

Question 5

Why are Enzyme-substrate bonds weak but numerous?

Answer 5

To ensure specificity and reversibility

Question 6

What is molecular complementarity in terms of enzymes?

Answer 6

When enzyme and substrate have complementary atoms/functional groups that bind precisely to one another in the active site

Question 7

What are the 4 types of enzyme-substrate bonds?

Answer 7

Ionic bonds, hydrogen bonds, van der Waal’s interactions, covalent bonds

Question 8

What are ionic enzyme-substrate bonds?

Answer 8

Attractions between charged (protonated/deprotonated) amino acid side chains

Question 9

What are hydrogen enzyme-substrate bonds?

Answer 9

H-bonds between side chain or backbone O and N atoms of amino acids

Question 10

What are enzyme-substrate van der Waals interactions?

Answer 10

Interactions between any protein and substrate atoms in close proximity

Question 11

What is the weakest type of chemical bond?

Answer 11

van der Waals/dispersion forces

Question 12

What are covalent enzyme-substrate bonds?

Answer 12

A rare type of strong bond between atoms of the substrate and protein atoms

Question 13

How are active sites stereospecific?

Answer 13

If the active sites are asymmetric, they can distinguish between stereoisomers (D or L)

Question 14

What are the 2 types of enzyme-substrate binding model?

Answer 14

Lock & Key and Induced Fit

Question 15

What is the principle of the lock & key model?

Answer 15

The shape of the substrate and the conformation of the active site are complementary to each other, so no shape change is needed.

Question 16

What is the principle of the Induced Fit Model?

Answer 16

Enzymes must undergo conformational changes upon binding to the substrate, in order for the active site to have a shape complementary to the substrate

Question 17

Are enzymes dynamic or static in terms of shape?

Answer 17

Dynamic

Question 18

What are the 3 ways that enzymes lower activation energy?

Answer 18

Ground state destabilisation, Transition state stabilisation, Alternate reaction pathway with a different transition state

Question 19

How do enzymes lower activation energy via ground state destabilisation?

Answer 19

By having an active site that has shape/charge complementarity to the transition state, rather than the substrate

Question 20

How do enzymes lower activation energy via transition state stabilisation?

Answer 20

By having an active site that has shape/charge complementarity to the transition state, rather than the substrate.

Question 21

What are the 5 key catalytic mechanisms?

Answer 21

Preferential binding of the transition state, proximity & orientation effects, acid-base catalysis, metal ion catalysis and covalent catalysis

Question 22

What are transition state analogues?

Answer 22

Chemicals that resemble the transition states of substrates but are more stable, so can bind to the relevant enzymes, inhibiting natural substrate reactions

Question 23

What are the proximity and orientation mechanisms of enzymes?

Answer 23

Enzymes can hold substrates in the correct position (close together and in correct orientation) to readily react

Question 24

What is acid-base catalysis in terms of enzymes?

Answer 24

When amino acids in the active site are involved in proton transfer (loss at low pH and gain at high pH) to facilitate the reaction

Question 25

What amino acid is commonly involved in a acid-base catalysis, and why?

Answer 25

Histidine, because its pKa is close to physiological pH and therefore can accept or donate protons depending on the environment of the active site

Question 26

What are the 3 key functions of metal ions in catalysis?

Answer 26

Substrate orientation, act as Lewis Acid, site of electrons transfer

Question 27

What is the substrate orientation functions of metal ions in catalysis?

Answer 27

Able to orientate substrate within the active site due to specific coordination geometries

Question 28

What is the Lewis Acid function of metal ions in catalysis?

Answer 28

Ability to act as Lewis acids/electron pair acceptors to polarise H2O or other functional groups

Question 29

What is the electron transfer function of metal ions in catalysis?

Answer 29

Allow for electron transfer reactions such as redox reactions, which can be used to balance the negative charge of transition states, bringing down the activation energy

Question 30

What is covalent catalysis in terms of enzymes?

Answer 30

Involves the formation of a reactive, short-lived intermediate, e.g. nucleophilic side chain, which is covalently attached to the enzyme