Enzymes Structure and Funtion - Done

Question 1

What enzyme catalyses the conversion of pyruvic acid to lactic acid?

Answer 1

LDH - lactate dehydrogenase (enzyme)

Question 2

Give ways as to how enzymes catalyse reactions

Answer 2

Provide a reaction surface (active site) - weakening of high-energy bonds

Provides a suitable environment (hydrophobic)

Brings reactants together - holds substrate in correct orientation to increase the chances of reaction

Enzymes catalyse both forward and backward reactions

Provide acid/base catalysis

Provides nucleophilic groups - serine / cysteine

Stabilises the transition state with intermolecular bonds

Question 3

What’s the benefit of active sites being more hydrophobic than enzyme surface?

Answer 3

Provides suitable environment for many reactions that would be difficult/impossible in aqueous environment

Question 4

Define activation energy

Answer 4

The difference between the transition state and the substrate - determines rate of reaction

Question 5

What is the ∆G in reaction pathways?

Answer 5

The difference in energy between the starting material and the product

∆G doesn’t change when using enzyme or not

Question 6

What equation gives the energy difference of reaction pathways?

Answer 6

E = ∆G = -RTlnK

Question 7

What equation gives the rate constant of a reaction?

Answer 7

Rate constant = k = A exp(-E/RT)

Question 8

How do you find the equilibrium constant K?

Answer 8

K = [products] / [reactants]

Question 9

What does hydrogen bonding take place between?

Answer 9

An electron-deficient hydrogen and an electron-rich heteroatom (N or O)

Question 10

How is hydrogen bonding unlike other intermolecular forces?

Answer 10

Involves orbitals and is directional

Optimum orientation is 180˚ between X, H and Y

Question 11

Give 2 examples of strong HBAs

Answer 11

Carboxylate ion and phosphate ion

Question 12

Give 3 examples of moderate/good HBAs

Answer 12

Moderate:

Carboxylic acid
Amide oxygen
Ketone
Ester
Ether
Alcohol

Tertiary amine - Good

Question 13

Give 3 examples of poor HBAs

Answer 13

Sulphur
Fluorine
Chlorine
Aromatic ring
Amide nitrogen - lone pair tied up
Aromatic amine - delocalised ring

Question 14

Give 2 examples of good HBDs

Answer 14

Aminium ion - HNR3
Secondary amine
Primary amine

Question 15

What’s the importance of dipole moments in drugs?

Answer 15

Dipoles align the drug as it enter the binding site - orienting the molecule

Can be beneficial or detrimental if groups aren’t positioned correctly

Question 16

How do induced dipole interaction occur? Give an example of this.

Answer 16

Where the charge on one molecule induces a dipole on another

Quaternary ammonium ion and an aromatic ring

Question 17

What is the role of water in drug binding?

Answer 17

Water solvates the drug and its target, so before binding can happen water must be stripped away.

If energy required to solvate both the drug and binding site is > the stabilisation energy gained by the binding interactions then the drug may be ineffective - ensure ∆G < 0

Question 18

What’s the problem with hydrophobic interactions and water when binding?

Answer 18

Surrounding water molecules form stronger than usual interactions with each other - more ordered layer of water next to non-polar surface

This represents negative entropy due to an increase in order

Water is freed when hydrophobic regions interact - becoming less ordered and increasing entropy and a gain in binding energy

Question 19

What is Koshland’s induced fit theory?

Answer 19

Active site changes shape when substrate enters

Substrate induces active site to take up ideal conformation to accommodate it - substrate may also alter its shape to maximise bonding interactions

Enzyme also binds to the transition state, stabilising state and lowering activation energy

Question 20

How does histidine often provided acid/base catalysis?

Answer 20

Acts as a weak base - both protonated and free forms exist at equilibrium

Question 21

Show the hydrolysis of peptide bonds catalysed by chymotrypsin.

Answer 21

GN5 pages 9 & 10

Question 22

What are cofactors?

Answer 22

Additional non-protein substances required by many enzymes for a reaction to take place

Question 23

What are co-enzymes?

Answer 23

Metal ions or small organic molecules (Zinc & NAD+)

Most bind by ionic and non-covalent interactions

Question 24

What are prosthetic groups?

Answer 24

Covalently bound co-factors

Question 25

What co-enzyme does lactate dehydrogenase require?

Answer 25

Nicotinamide adenine dinucleotide (NAD+)

Question 26

What type of reaction do lyases catalyse?

Answer 26

Addition or removal of groups to form double bonds

Question 27

What type of reaction do ligases catalyse?

Answer 27

Joining 2 substrates at the expense of ATP hydrolysis

Question 28

What type of reaction do isomerases catalyse?

Answer 28

Isomerisation and intramolecular group transfer

Question 29

What is genetic polymorphism and its effect?

Answer 29

Subtle differences in structure and properties of proteins between individuals

Can lead to genetic disease or have an effect on drug therapy - due to differences in metabolism

Question 30

Why is an allosteric site needed for feedback inhibition?

Answer 30

As product will have undergone many transformations and is no longer recognised by the active site - allosteric site needed

Question 31

How do kinases control activity within the cell?

Answer 31

By phosphorylation amino acids
- can activate or deactivate enzymes

Question 32

What is external control?

Answer 32

Usually initiated by external messengers which do not enter the cell

Question 33

What is the importance of nitric oxide?

Answer 33

Nitric oxide passes through the surface membrane and activates cyclases to generate cyclic GMP - secondary messenger which influences other reactions within the cell.

Hence NO has an influence on a diverse range f processes within the cell

Question 34

Where do the isozymes of lactate dehydrogenase (LDH) act predominantly respectively?

Answer 34

H predominates in heart muscle

M predominates in skeletal muscle

Question 35

How many different isozyme of LDH are there?

Answer 35

5
HHHH
HHHM
HHMM
HMMM
MMMM

Their properties differ - reactivity