Dugga 1 Flashcards
What do agonists do?
mimic the natual ligand
What do antagonists do?
Bind to the receptor but do not activate it
Do antagonists bind to regions of the receptor that are not involved in binding the natural ligand?
Yes
What do partial agonists do?
They induce a weaker effect than a full agonist
What is an inverse agonist?
Acts as an antagonist and also eliminate any resting activity
What is desensitisation?
When an agonist is bound to its receptor for a long time
What is sensitisation?
When an antagonist is bound to a receptor for a long time, the cells synthesise more receptors to counter the effect
What is tolerance?
When an increased dose is required over time to achieve same effect
What is dependence?
The body’s ability do adapt to the presence of a drug
What is pharmacodynamics?
How drugs interact with their targets to produce a pharmacological effect
“What the drug does to the body”
What is pharmacokinteics?
The study of factors that affect the ability of the drug to reach its
target in the body
“What the body does to the drug”
What is affinity?
A measure of how strongly a drug binds to a receptor
What is efficacy?
A measure of the effect of the binding of a drug on the cell
What is potency?
How effective a drug is in producing a cellular effect
What sorts of molecules do transport proteins transport?
Polar molecules
What can drugs that target viral structural proteins do?
Prevent viruses from entering the cell and inhibit the uncoating
What is tubulin?
A structural protein crucial to cell division and mobility
What do vinca alkaloids do to tubulin?
Bind and inhibit the polymerisation process
What does paclitaxel do to tubulin?
Bind and accelerate polymerisation by stabilising resulting microtubules
How does a drug targeting lipids work?
Disrupting the lipid structure of cell membranes
What do tunelling molecules and ion carriers do to the plasma membrane and to the cell?
They result in uncontrolled movement of ions across the cell membrane leading to cell death
What is valinomycin?
A cyclic structure with alternating ester and amide bonds and acts as a ion carrier
What is the definition of a drug target?
A macromolecule that has a binding site where the drug binds
How do drugs bind their target?
Intermolecular bonds
Where do hydrogen bonds occur?
Between an electron rich heteroatom and an electron deficient hydrogen
What are hydrophobic interactions?
The displacement of ordered layer of water molecules that surround hydrophobic regions. This increases entropy.
What needs to happen to polar groups before intermolecular interactions can take place?
They have to be desolvated
What is the primary structure?
The order in which amino acids are linked together
What is the secondary structure?
Regions of ordered structure within the protein such as alpha helices, beta pleated sheets and beta turns
What is the tertiary structure
The overall three dimensional shape, how the alpha and beta regions are ordered and linked by interactions
What is he quarternary structure?
Proteins containing two or more subunits, how the subunits are arranged
How are the structures determined?
To maximise the favourable intramolecular and intermolecular bonds and minimise unfavourable interactions
Where are the polar residues typically favoured?
On the outside of the protein because this allows for interactions with water
What is proteomics?
The study of the structure and function of novel proteins discovered through genomics
What are common drug targets?
Transport proteins, enzymes and receptors
What do transport proteins do?
Transport essential polar molecules across the hydrophobic cell membrane
What is tubulin?
A structural protein crucial to cell division and mobility
How does a substrate bind to an active site?
With intermolecular bonds
When a substrate binds in an enzyme, the shape of the active site may change to maximise binding interactions and in this process what may happen to the bonds in the substrate?
It may weaken crucial bonds
The amino acid histine is often present in the active site, what does it do?
It acts as an acid/base catalyst
The amino acid histine is often present in the active site to act as an acid/base catalyst, which other amino acids may be present?
Glutamic acid, aspartic acid, tyrosine
Which amino acids act as nucleophiles in the reacton mechanism of some enzymes?
Serine and cysteine. In some enzymes lysine
What are cofactors?
Metal ions or small organic molecules. They can be viewed as the body’s chemical reagents.
What is a prothetic group?
A cofactor bound covalently to an enzyme
What is an allosteric inhibitor?
Binds to a different binding site and alters the shape of the enzyme so that the active site nolonger works. Often involved in feedback control of biosynthetic pathways
What is an isozyme?
A variation of the same enzyme. Catalyse same reaction but differ in primary structure, substrate specificity and tissue distribution
What does the Michaelis Menten equation relate?
The rate of an enzyme catalysed reaction to the substrate concentration
What is the Michaelis contant equal to?
The substrate concentration at which the rate of enzyme catalysed reaction is half of its max value
What does G protein coupled receptors activate?
G proteins
How many transmembrane section does a G protein coupled receptor have?
7
Where is the C and N terminals located in a G protein coupled receptor?
The C terminal is within the cell and the N terminal outside the cell
Receptor types have subtypes. Is it possible for a drug to target only one subtype of the receptor?
Yes
Intracellular receptors are located within the cell and are important in controlling…
transcription
How does a chemical messenger for an intracellular receptor pass through the cell membrane?
It must be sufficiently hydrophobic
What does a G protein consist of?
3 protein subunits of which the alpha one is bound to the G protein
What happens to the G protein coupled receptor when a ligand binds?
GDP is exchanged for GTP which the G protein fractions into an alpha subunit and a beta gamma subunit
What does the alpha s subunit bind to?
Adenylate cyclase catalysing the formation of cAMP from ATP
What does the alpha i subunit do?
Inhibits adenylate cyclase
What does cAMP do?
Acts as a secondary messenger and activates PKA
What does PKA do?
It catalyses the phosphorylation of serine and threonine residues in other enzymes
What are tyrosine kinases?
Enzymes that phosphorylate the phenol group of tyrosine. Phosphorylation is a conformational change that affects the activity of the substrate enzyme
What do intracellular receptors do?
Regulate gene transcription
