Lecture 13 - Activation and inhibition of proteins Pt. I

Question 1

What is pharmacology the study of?

Answer 1

science of the effects of drugs on biological systems, from the molecular level to patient studies.

Question 2

What is toxicology the study of?

Answer 2

similar to pharmacology but specialises in the study of the harmful effects of drugs and other chemicals

Question 3

What factors can play a hugge role in what effect they have?

Answer 3

dose, and route of administration

Question 4

What drug is rat poison in high doses but low doses prevent blood clots after a stroke or heart attack?

Answer 4

Warfarin

Question 5

How do substances cause harm or have a positive health benefit?

Answer 5

They can activate or inhibit proteins

Question 6

What are harmful substances called?

Answer 6

toxins or poisons

Question 7

What are beneficial substances called?

Answer 7

medicines or drugs

Question 8

What are the common steps of a substance causing a harmful or beneficial response?

Answer 8

1. Chemical substance travels from source
2. Binds to protein (binding/reception)
3. Protein activation or inhibition
4. Changes cellular response

Question 9

What is a receptor?

Answer 9

a cellular protein or assembly of proteins that controls chemicals signalling between and within cells

Question 10

How many individual receptor proteins are there?

Answer 10

~1000

Question 11

What are some physiological responses receptors control?

Answer 11

sight, smell, taste, etc.

Question 12

What proportion of drugs activate or inhibit receptors?

Answer 12

at least one third

Question 13

What is the difference between enzyme and receptors binding sites?

Answer 13

enzymes have one active site, receptors may have several binding sites

Question 14

What is the difference between what enzymes and ligands bind?

Answer 14

enzymes bind substrates, receptors bind ligands

Question 15

What does an enzyme do to a substrate upon binding?

Answer 15

turns it into a PRODUCT

Question 16

What does a receptor do to a ligand upon binding?

Answer 16

Releases ligand UNCHANGED

Question 17

Where are both enzymes and receptors found?

Answer 17

membrane bound or free in cytosol

Question 18

What are some similarities between enzymes and receptors?

Answer 18

both can be activated or inhibited, and used as drug targets

Question 19

What are the main classes of receptor?

Answer 19

Question 20

What are ligands?

Answer 20

Very diverse in chemical structure can be small molecules to large peptides and proteins

Question 21

What is the general term given to a chemical substance that specifically binds to a receptor?

Answer 21

a ligand

Question 22

What are endogenous ligands?

Answer 22

ligands produced all over the body

Question 23

What are exogenous ligands?

Answer 23

Ligands produced outside of the body

Question 24

What are some examples of exogenous ligands?

Answer 24

drugs, and toxins

Question 25

What do all ligands do?

Answer 25

make chemical contacts with their specific receptors

Question 26

Where are most receptors found in the cell?

Answer 26

outer cell membrane

Question 27

What role do receptors on the outer cell membrane play?

Answer 27

Act as sensors of the extracellular environment

Question 28

Does the ligand usually need to pass through the membrane to activate a receptor?

Answer 28

No, usually not

Question 29

What is the first step in the process of actually activating the receptor?

Answer 29

binding of the ligand to the receptor (reception)

Question 30

What is the role of the receptor in cellular activity?

Answer 30

The receptor acts as a ‘gate keeper’ of cellular activity, controlling it from the cell surface

Question 31

How can intracellular responses to extracellular signals be produced?

Answer 31

by a membrane receptor being activated

Question 32

There is …. between ligands and receptors

Answer 32

specificity (only correct pairing will result in activation or inhibition)

Question 33

What allows binding to occur between a ligand and receptor?

Answer 33

the size and shape of the ligand must match the corresponding receptor binding pocket, allowing enough chemical interaction for binding to occur

Question 34

How do medicinal chemists often make safe and effective medicines?

Answer 34

by producing a molecule that closely mimics an endogenous ligand, so will bind to the same receptors. ie. salbutamol can bind to the same receptors as adrenaline (an endogenous ligand))

Question 35

How does salbutamol work?

Answer 35

Activates the same receptors as adrenaline, mimicking its effects causing bronchodilation

Question 36

What is an agonist?

Answer 36

a chemical substance that binds to a receptor and activates it

Question 37

How is a receptor activated?

Answer 37

undergoes a conformational (shape) change

Question 38

How does ACTIVATION of a receptor change cellular response?

Answer 38

active receptor starts signal transduction

Question 39

what is signal transduction?

Answer 39

when an active receptor starts a chain of events in which messages are passed on through the cell. (messages are passed on by different relay molecules depending on the receptor)

Question 40

What is an antagonist?

Answer 40

A ligand that binds to a receptor and prevents activation BY an agonist

Question 41

How does an antagonist change the cellular response?

Answer 41

inhibition - doesn’t allow signal transduction to occur

Question 42

How are agonists and antagonists similar?

Answer 42

make specific chemical contacts with receptors

Question 43

How do agonists and antagonists differ?

Answer 43

despite binding in a similar position only the chemical contacts made by an agonist are sufficient to cause a conformation change in the receptor

Question 44

How does adrenaline work?

Answer 44

1. Acts as an agonist to activate the a GPCR called the Beta- adrenergic receptor
2. Signal transduction
3. Bronchodilation

Question 45

How does Insulin work?

Answer 45

1. Acts as an agonist to activate the insulin receptor (a RTK)
2. Signal transduction
3. Glucose uptake

Question 46

Why are receptors so important in making drugs?

Answer 46

Chemical substances commonly act via receptor to change the cellular response