Lecture 13 - Activation and inhibition of proteins Pt. I Flashcards
What is pharmacology the study of?
science of the effects of drugs on biological systems, from the molecular level to patient studies.
What is toxicology the study of?
similar to pharmacology but specialises in the study of the harmful effects of drugs and other chemicals
What factors can play a hugge role in what effect they have?
dose, and route of administration
What drug is rat poison in high doses but low doses prevent blood clots after a stroke or heart attack?
Warfarin
How do substances cause harm or have a positive health benefit?
They can activate or inhibit proteins
What are harmful substances called?
toxins or poisons
What are beneficial substances called?
medicines or drugs
What are the common steps of a substance causing a harmful or beneficial response?
- Chemical substance travels from source
- Binds to protein (binding/reception)
- Protein activation or inhibition
- Changes cellular response
What is a receptor?
a cellular protein or assembly of proteins that controls chemicals signalling between and within cells
How many individual receptor proteins are there?
~1000
What are some physiological responses receptors control?
sight, smell, taste, etc.
What proportion of drugs activate or inhibit receptors?
at least one third
What is the difference between enzyme and receptors binding sites?
enzymes have one active site, receptors may have several binding sites
What is the difference between what enzymes and ligands bind?
enzymes bind substrates, receptors bind ligands
What does an enzyme do to a substrate upon binding?
turns it into a PRODUCT
What does a receptor do to a ligand upon binding?
Releases ligand UNCHANGED
Where are both enzymes and receptors found?
membrane bound or free in cytosol
What are some similarities between enzymes and receptors?
both can be activated or inhibited, and used as drug targets
What are the main classes of receptor?
What are ligands?
Very diverse in chemical structure can be small molecules to large peptides and proteins
What is the general term given to a chemical substance that specifically binds to a receptor?
a ligand
What are endogenous ligands?
ligands produced all over the body
What are exogenous ligands?
Ligands produced outside of the body
What are some examples of exogenous ligands?
drugs, and toxins
What do all ligands do?
make chemical contacts with their specific receptors
Where are most receptors found in the cell?
outer cell membrane
What role do receptors on the outer cell membrane play?
Act as sensors of the extracellular environment
Does the ligand usually need to pass through the membrane to activate a receptor?
No, usually not
What is the first step in the process of actually activating the receptor?
binding of the ligand to the receptor (reception)
What is the role of the receptor in cellular activity?
The receptor acts as a ‘gate keeper’ of cellular activity, controlling it from the cell surface
How can intracellular responses to extracellular signals be produced?
by a membrane receptor being activated
There is …. between ligands and receptors
specificity (only correct pairing will result in activation or inhibition)
What allows binding to occur between a ligand and receptor?
the size and shape of the ligand must match the corresponding receptor binding pocket, allowing enough chemical interaction for binding to occur
How do medicinal chemists often make safe and effective medicines?
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))
How does salbutamol work?
Activates the same receptors as adrenaline, mimicking its effects causing bronchodilation
What is an agonist?
a chemical substance that binds to a receptor and activates it
How is a receptor activated?
undergoes a conformational (shape) change
How does ACTIVATION of a receptor change cellular response?
active receptor starts signal transduction
what is signal transduction?
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)
What is an antagonist?
A ligand that binds to a receptor and prevents activation BY an agonist
How does an antagonist change the cellular response?
inhibition - doesn’t allow signal transduction to occur
How are agonists and antagonists similar?
make specific chemical contacts with receptors
How do agonists and antagonists differ?
despite binding in a similar position only the chemical contacts made by an agonist are sufficient to cause a conformation change in the receptor
How does adrenaline work?
- Acts as an agonist to activate the a GPCR called the Beta- adrenergic receptor
- Signal transduction
- Bronchodilation
How does Insulin work?
- Acts as an agonist to activate the insulin receptor (a RTK)
- Signal transduction
- Glucose uptake
Why are receptors so important in making drugs?
Chemical substances commonly act via receptor to change the cellular response
