Lecture 8

Question 1

Where does enzyme - substrate binding occur?

Answer 1

At 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

Why are weak bonds advantageous?

Answer 7

Can only form if the relevant atoms are precisely positioned and they are easy to break

Question 8

What are types of enzyme-substrate bond?

Answer 8

Ionic bonds, hydrogen bonds, van der waals interactions, covalent bonds

Question 9

What are ionic enzyme-substrate bonds?

Answer 9

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

Question 10

What are hydrogen enzyme-substrate bonds?

Answer 10

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

Question 11

What are enzyme-substrate van der Waals interactions?

Answer 11

Interactions between any protein and substrate atoms in close proximity

Question 12

What is the weakest type of chemical bond?

Answer 12

Van der Waals/dispersion forces

Question 13

What are covalent enzyme-substrate bonds?

Answer 13

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

Question 14

How are active sites stereospecific?

Answer 14

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

Question 15

What are the two types of enzyme-substrate binding models?

Answer 15

Lock and Key and Induced fit

Question 16

What is the lock and key model?

Answer 16

The shape of the substrate and the conformation of the active site are complementary to one another

Question 17

What is the induced fit model?

Answer 17

The enzyme undergoes a conformational change upon binding to the substrate. The shape of the active site becomes complementary to the shape of the substrate only after binding to the enzyme

Question 18

Are enzymes dynamic or static?

Answer 18

Dynamic

Question 19

How is ∆G‡ lowered?

Answer 19

Ground state destabilisation, transition state stabilisation and alternate reaction pathway with a lower energy transition state

Question 20

What are the five catalytic mechanisms

Answer 20

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

Question 21

What is the prediction of preferential binding of the transition state?

Answer 21

An enzyme should bind the transition state more tightly than it binds the substrate

Question 22

What is the problem of preferential binding of the transition state?

Answer 22

Transition states are transient and cannot be isolated -> need to design and synthesise an analogue

Question 23

What are transition state analogues as drugs?

Answer 23

Enzymes are often targets for drugs and other beneficial agents, analogues often make ideal enzyme inhibitors

Question 24

What is the function of enalapril and aliskiren?

Answer 24

To lower blood pressure

Question 25

What is the function of statins?

Answer 25

To lower serum cholesterol

Question 26

What is the function of protease inhibitors?

Answer 26

AIDS drugs

Question 27

What is the function of juvenile hormone esterase?

Answer 27

To target pesticides

Question 28

What is the function of tamiflu?

Answer 28

An inhibitor of influenza neuraminidase

Question 29

What are the proximity and orientation effects?

Answer 29

For two molecules to react they need to be close together and in the right orientation

Question 30

What is acid-base catalysis?

Answer 30

Involves H+ transfer

Question 31

Why is histidine suitable for acid-base catalysis?

Answer 31

Because its pKa is ~6.5 which is close to physiological pH and it can donate and accept protons

Question 32

What do metal ion catalysis provide?

Answer 32

Substrate orientation, ability to act as a lewis acid, sites for electron transfer (RedOx)

Question 33

How does hexokinase use Mg2+ as a cofactor?

Answer 33

Mg2+ ion balances negative charge of transition state (2x O-)

Question 34

Describe covalent catalysis

Answer 34

The formation of a very reactive and short-lived intermediate which is covalently attached to the enzyme