Enzymes as a drug target

Question 1

List 6 factors that impact enzyme activity

Answer 1

pH
Temperature
regulatory molecules
Co-factors
Compartmentalisation 
Feedback inhibition

Question 2

How do regulatory molecules impact enzyme activity?

Answer 2

Can turn enzymes up or down

Question 3

How do co-factors impact enzyme activity?

Answer 3

Some enzymes are only active when bond to co-factors

Question 4

How does compartmentalisation impact enzyme activity?

Answer 4

Storing enzymes in specific compartments can provide the right conditions for activity

Question 5

How can feedback inhibitors impact enzyme activity?

Answer 5

Enzymes are inhibited by the end product of the pathway they control

Question 6

What are activators?

Answer 6

Increase enzyme activity

Question 7

What are inhibitors?

Answer 7

Decrease enzyme activity

Question 8

What is reversible inhibition?

Answer 8

The binding is reversible

Question 9

What is a competitive inhibitor?

Answer 9

Inhibitor binds and blocks binding site of substrate
Will decrease rate of reaction when not much substrate but can be out-competed by increasing substrate concentration (can reach maximum rate)

Question 10

What is a non-competitive inhibitor?

Answer 10

Inhibitor binds to allosteric site

Never reach maximum rate - the enzymes are ‘poisoned’ and can’t do job

Question 11

What is allosteric regulation?

Answer 11

Regulatory molecule binds to allosteric site
Most non-competitive inhibitors
When binds to enzyme, all active sites on protein subunits are changed slightly

Question 12

What are allosteric enzymes?

Answer 12

Enzymes that are allosterically regulated with unique properties, typically have multiple active sites

Question 13

What are allosteric activators?

Answer 13

Bind to locations other than active site, causing increase in function of active site

Question 14

What is cooperactivity?

Answer 14

Substrate serves as allosteric activator - when it binds to one active site, the activity of the other increases

Question 15

Characteristics of co-factors

Answer 15

Help enzymes for optimally
Can be temporarily attached by hydrogen/ionic bonds
Can be permanently attached by ionic bonds

Question 16

What are co-enzymes?

Answer 16

Subset of co-factors that are carbon based

e.g. dietary vitamind

Question 17

What is compartmentalisation?

Answer 17

Stored in specific part of cell so enzymes are kept where they’re needed and can find substrates readily, as well as maintaining an optimum microenvironment

Question 18

What is feedback inhibition?

Answer 18

The end product of a metabolic pathway acts on the key enzyme to prevent more of the end product from being produced
Means that the existing supply is used up rather than making excess of the end product
Typically acts as first committed step (irreversible step)
Can act at multiple points along pathway

Question 19

Example of feedback inhibition using ATP

Answer 19

ATP is allosteric inhibitor of enzymes involved in respiration
Lots of ATP = feedback inhibition = no new ATP
ATP is unstable so will be broken down quickly
ADP = allosteric activator for enzymes inhibited by ATP
When ADP>ATP, respiration enzymes are active and make more ATP

Question 20

Symptoms of myasthenia gravis

Answer 20

Fatiguability and becomes weaker

Question 21

How can you treat myasthenia gravis?

Answer 21

Thymectomy
Steroids
Immunosuppressants
Pyridostigmine

Question 22

What does pyridostigmine do?

Answer 22

Prevents breakdown of acetylcholine

Question 23

What are regulatory molecules?

Answer 23

Activation and competitive vs non-competitive inhibitors, allosteric binding, induces conformational change

Question 24

What are co-factors and co-enzymes?

Answer 24

Additional molecules, co-factors are inorganic and co-enzymes are organic (e.g. magnesium or iron)

Question 25

What is compartmentalisation?

Answer 25

Enzymes stored in place with specific environment and they can’t function outside this environment (e.g. stomach enzymes and pH)

Question 26

What is feedback inhibition?

Answer 26

The end product of a pathway inhibits an earlier stage of the same pathway (e.g. ADP and ATP)

Question 27

What is a kinase molecule?

Answer 27

Catalyses transfer of phosphate from high-energy, phosphate-donating molecules to specific substrates via phosphorylation

Question 28

What is a dehydrogenase molecule?

Answer 28

Removes/transfers hydrogen from a substrate

Question 29

What is a phosphatase molecule?

Answer 29

Uses water to cleave phosphoric acid monoester into phosphate ion and alcohol

Question 30

What is a synthase molecule?

Answer 30

Catalyses synthesis of two molecules

Question 31

What is a protease molecule?

Answer 31

Catalyses proteolysis by cleaving peptide bonds between peptides by hydrolysis

Question 32

What is a lipase molecule?

Answer 32

Catalyses breakdown of lipids by hydrolysis

Question 33

What is IC50?

Answer 33

Half maximal inhibitory concentration (measures how potent an inhibitory molecule is). Measures how much of an inhibitor is needed to reduce the activity of an enzyme by 50%

Question 34

What does SOCRATES stand for when doing a consultation?

Answer 34

• Site
• Origin
• Characteristics
• Radiation of pain
• Associated symptoms
• Timing of pain
• Exacerbating factors
• Severity of pain

Question 35

What doe NSAIDs do?

Answer 35

Inhibit the cyclooxygenase enzymes

Question 36

What does COX 2 do?

Answer 36

Creates prostaglandins that lead to inflammation

Question 37

What does COX 1 do?

Answer 37

Normal physiological function

Question 38

Why do NSAIDs normally cause a lot of side-effects?

Answer 38

The drugs are non-specific and so wear down stomach lining

Question 39

What are the four enzymes that act on arachidonic acid?

Answer 39

Cyclooxygenase, phospholipase, 5-lipoxygenase, 12-lipoxygenase