Enzymes as drug targets

Question 1

What are enzymes?

Answer 1

1. Enzymes are specialised protein binding sites that are specific for certain substrates
2. Once bound, substrate is modified
3. Binding pocket is the active site

Question 2

Explain the kinetics behind enzymes?

Answer 2

Enzymes are catalysts that alter the activation energy of a particular reaction

Question 3

What is the Vmax?

Answer 3

The maximum rate at which an enzyme can carry out a reaction

Question 4

What is the Km?

Answer 4

Substrate concentration at which the enzyme will work at 1/2 Vmax

Question 5

How do you plot the graph of an enzyme?

Answer 5

Reaction rate against the substrate concentration

Question 6

How does a reaction occur in an enzyme?

Answer 6

1. Substrate enters enzymes activate site
2. Enzyme binded substate
3. Enzyme releases product

Question 7

How does competitive inhibition work in an enzyme?

Answer 7

1. Inhibitor attaches to the active site (shares steric properties)
2. Prevents the substrate binding and competes with the substrate

Question 8

What does the Ki constant represent?

Answer 8

Ki is the constant that describes how frequently the inhibitor binds to the enzyme or the enzyme substrate

Question 9

What is the line weaver burke plot?

Answer 9

1. Plots the 1/v (velocity) and the 1/s (substrate concentration)
2. Allows you to work out Vmax and Km easily

Question 10

How are enzymes used as drug targets for infectious agents?

Answer 10

1. Enzymes produced by infectious agents can be switched off- fatal for bacteria or virus
2. Bactericidal drugs target enzymes produced by humans
3. Viral enzymes can be targeted to prevent viral replication

Question 11

Give an example of a class of drugs used against bacteria? And describe how it works?

Answer 11

1. Penicillin (Penicillin binding protein) aka DD transpeptidases
2. Carries out cross linking of peptidoglycan wall subunits for bacteria
3. Beta lactam antibiotics bind to and irreversibly inhibit the DD transpeptidases that help rebuild the peptidoglycan wall

Question 12

How do bacteria counter beta lactam drugs?

Answer 12

1. Contain a protein and enzyme called bata lactamases for bacteria resistance
2. Can be transferred from viruses to viruses

Question 13

Describe how HIV protease works?

Answer 13

Central to HIV replication as it processes and cleaves viral virion proteins required for formation of active virus

Question 14

Explain how atazanavir works?

Answer 14

1. Will prevent the protease from HIV from processing HIV proteins from replicate
2. Will reduce amount of circulating virus so reduces immunodeficient response

Question 15

Why might we want to target and change human enzymes?

Answer 15

1. Can change the physiological function of the enzyme through changing protein sequence
2. Caused mutations lead to human diseases and altered enzyme function
3. Drugs can correct these changes

Question 16

What is ACE and describe its role?

Answer 16

1. ACE= Angiotensin converting enzyme

Involved in regulating the function of the kidney

2. Acts as a protease to cleave Angiotensin I and converts it to Angiotensin II (active form of peptide)
3. Can cause increase in water retention

Question 17

Describe how ACE inhibitors work? And give an example?

Answer 17

1. Inhibit the activity of ACE which leads to the decrease in the production of Angiotensin II
2. This decreases fluid retention and results in lower blood pressure
3. Example: Ramipril

Question 18

Describe how cyclo-oxygenase works?

Answer 18

Synthesises prostaglandins which are involved in the inflammatory response

Question 19

Describe how COX inhibitors work?

Answer 19

1. Reduce the synthesis of prostaglandin by inhibiting the COX enzymes
2. So it can reduce the generation of heat and body temperature

Question 20

Give an example of COX inhibitor?

Answer 20

Ibuprofen and other NSAIDS

Question 21

Describe how protein kinases work and give an example of where they are used?

Answer 21

1. Protein kinases are key regulatory enzymes that regulate a whole range of proteins
   through the addition of the phosphate group
2. Form an integral part of signalling cascades within the cell
3. Hydrolyse the ATP, transferring gamma phosphate into other molecules

Question 22

What is allosteric modulation?

Answer 22

1. When the drug can alter the enzymatic function by binding to sites distant fro the actual active site
2. Alter overall protein shape (conformation) which can lead to altered substrate binding or active site function