L10: How Enzymes Catalyse

Question 1

This is a specific site on the enzyme that has specific amino side chains projecting into it .

Answer 1

Active site

Question 2

What determines the specificity of reactions? Why?

Answer 2

The active site determines the specificity of a reaction. This is because the side chains are a key part of the active site, and the side chains determine the function of a protein

Question 3

What kind of interactions enable the substrate to bind into the active site?

Answer 3

Weak interactions

Remember: multiple weak interactions form strong bonds between molecules

Question 4

Why do we want the substrate to not bind so tightly to the active sight of the enzyme? use LOGIC it is not that hard of a question so think about it

Answer 4

Because we don’t want the substrate to not be able to reach the activation energy.

The substrate staying in substrate minima means it will require even more energy to get it to overcome the AE.

Question 5

Weak interactions ensure what two advantages?

Answer 5

Specificity and reversibility

Question 6

Why are weak bonds advantageous in terms of reversability?

Answer 6

Because it is easier to break weak bonds, which means once the reaction is done, the substrate can unbind from the enzyme and the enzyme can be reused again.

Question 7

This refers to the complementary set of weak bonds that can accomodate specific substrates.

Answer 7

Molecular complementarity

Question 8

What are the 4 types of enzyme-substrate bonds?

Answer 8

Ionic bonds/salt bridges
Hydrogen bonds
Van der Waals interactions
Covalent bonds (opposites attract kind of bonds)

Question 9

These bonds make use of charged side chains (either acidic: Aspartate, Glutamate, or basic: Arginine, Lysine)

Answer 9

Ionic bonds

Question 10

These bonds are often classified as when the side chain of backbone O and N atoms can often act as hydrogen donors and acceptors.

Answer 10

Hydrogen bonds.

Question 11

These are bonds that involve interactions between any protein and substrate atoms in close proximity. It is the weakest bonds of the 4 enzyme-substrate bonds.

Answer 11

Van der Waals Interactions/Bonds

Question 12

These are the strongest of the bonds, and relatively rare when it comes to enzyme-substrate bonding.

Answer 12

Covalent bonds

Question 13

True or false. The active site is symmetric, which allows the enzyme to distinguish between identical groups on the substrate.

Answer 13

False. The active site is asymmetric - its asymmetry allows it to be specific to a specific enzyme

Question 14

What are the 2 models for enzyme-substrate binding?

Answer 14

Lock and key model and induced fit model

Question 15

What does the lock and key model for enzyme-substrate binding state?

Answer 15

The shape of the substrate ad the conformation of the active site are complementary to each other.

• the substrate perfectly fits into the enzyme.

Question 16

What is the problem with the lock and key model? What does it suggest?

Answer 16

That a) substrates perfectly fit into an enzyme for it specifically and b) that enzymes are static (unchanging) - which is a problem because one enzyme can be used for multiple different purposes (due to the nature of the amino side chains that are projecting into it)

Question 17

What does the induced fit model stat?

Answer 17

The enzyme undergoes a conformational shape change upon binding to the substrate.

So the shape of the active site becomes complementary to the shape of substrate only after the binding has occurred.

• it states that enzyme is not perfectly shaped to fit the substrate.

Question 18

What does the induced fit model suggest about the nature of enzymes?

Answer 18

That enzymes are dynamic and its active site can change depending on the substrate binding

Question 19

What are the 3 ways to reduce the activation energy? (In this case, activation energy is energy needed to reach the transition state)

Answer 19

1) Ground state destabilisation (lift energy of reactants)

2) Ground state stabilisation (stabilising transition state) (reducing activation energy)

3) Alternate reaction pathway with a different transition state (with a lower energy)

Question 20

How can 1 and 2 be achieved in the same way?

Answer 20

By having an active site that has shape/charge complementary to the substrate.

Remember: Ground state is referring ultimately to the nature of the active site; not the substrate

Question 21

What are the 5 catalytic mechanisms?

Answer 21

1) Preferential binding of the transition state
2) Proximity and orientation effects
3) Acid-base catalysis
4) Metal ion catalysis
5) Covalent catalysis

Question 22

What does the preferential binding of the transition state predict?

Answer 22

This predicts that an enzyme should bind the transition state more tightly than it binds the substrate.

• aka enzyme is shaped PREFERENTIALLY to transition state so that it will be more effective

Question 23

What is the problem with preferential binding of the transition state? How do we solve this issue?

Answer 23

Transition states are transient; meaning they only last for a short period of time - so they are more difficult to isolate

So we design and make analogues

Question 24

What are analogues?

Answer 24

Analogues are enzyme inhibitors -

they mimic the transition state of drugs/substrates to make enzyme-substrate complex viable and more effective.

Question 25

This is an example of a transition state analogue. It is a powerful cholesterol-lowering drug, as it inhibits HMG CoA reductase (biosynthetic pathway for cholesterol)

Answer 25

Lipitor

Question 26

These make ideal enzyme inhibitors.

Answer 26

Transition sate analogues

Question 27

If someone is taking Enalapril and Aliskiren what kind of condition would that be modulating or helping with?

Answer 27

Lower blood pressure (meaning they have high blood pressure)

Question 28

These lower serum cholesterol

Answer 28

Statins

Question 29

Why are enzymes often targeted for drugs and other beneficial agents?

Answer 29

Because enzymes can inhibit the function of normal metabolic pathways. (interfere with that, and you can create health impacts that improve health conditions)

Question 30

What are the 2 guidelines for molecules to successfully react with each other?

Answer 30

• they must be close to each other
• and react with the correct orientation

Question 31

This is a catalytic mechanisms that involves proton transfers ad side chains that can accept/donate protons.

Answer 31

Acid-base catalysis

Question 32

Why is Histidine particularly ideal to acid-base catalysis?

Answer 32

Because Histidine has a pKa of 6.5 => which is very close to physiological pH meaning it can move between different protonation states (depending on the environment of the active site)

pH > pKa = deprotonated (because it will be in base form)

pH < pKa = protonated (because it will be in acid form)

Helpful tip: to remember which is which, always think, is the pH greater or lower than the pKa? Lower than is always protonated (so acid form), and greater than is always deprotonated (so base form)

Question 33

This involves the use of metal ions for catalytic activity. Metals provide correct substrate orientation, act as Lewis acids, and provide sites for electron transfers (redox reaction)

Answer 33

Metal ion catalysts

Question 34

This involves the formation of a reactive, short-lived intermediate, which is covalently attached to the enzyme.

Answer 34

Covalent catalysis