pharmacodynamics - drug targets Flashcards
(19 cards)
what are the 2 most common type of drug target?
enzymes and receptors
state 3 types of enzymes in the body
intracellular, extracellular, membrane bound
enzyme definition
biological catalyst, made out of protein (globular)
how do enzymes work?
they catalyse reactions by providing an alternative reaction pathway with a transition state which is lower in energy/more stable, so activation energy is smaller
what makes enzymes good biological catalysts?
they provide a reaction surface/active site and a suitable environment
they bring reactant together and position them correctly for reaction
can destabilise reactants by weakening bonds
can provide acid/base catalysis or nucleophilic groups
give 2 ways enzymes can provide nucleophilic groups
there are 2 amino acids that can act as nucleophiles in enzymes:
L-serine, R = CH2OH
L-cystine, R = CH2SH
both of these R groups can attack via Sn1/2 mechanisms and covalently + reversibly bind to substrate
is serine or cystine a better nucleophile?
cystine is a better nucleophile, as S is in period 3 therefore electrons are further form the nucleus so its easier to donate lone pair, whereas O holds on more tightly to its lone pair as its in period 2
give an example of a acid catalyst enzymes provide
histidine - acts as a base through its sp2 N atom in its non-ionised form, and as an acid in its ionised form (after accepting H+)
- due to pH ~ 7.4 histidine is mostly found in its ionised bronsted acid form (as a proton source)
give an example of an acid catalyst enzymes provide
aspartic acid - acts as an acid through its carboxylic alcohol O in its non-ionised form, and as a base in its ionised COO- form
- due to pH ~ 7.4 aspartic acid is mostly found in its ionised bronsted base form (as a proton sink)
active site definition
a hydrophobic hollow or cleft on an enzyme surface which accepts reactants (either substrates or cofactors), able to do so because of the particular amino acids it is made of
does the active site fit the substrate perfectly?
nearly - induced fit model suggests that binding triggers a conformational change which improves the shape, making it mroe complementary
how does binding to the active affect the substrate?
strains bonds in substrates, weakening them and allowing the reaction to take place
give 4 IMFs involved in active site binding
ionic bonds
hydrogen bonds
van der waals forces
london/dispersion forces
receptor definition
globular proteins (permanently) bound to the surface of cell membranes that pass signals from exterior of cell to interior, via bonding to chemical messengers
how do receptors work?
receptors contain a binding site (similar to enzymes active site) which is complementary to a particular chemical messenger
chemical messenger can bind to receptor via many IMFs, causing conformational changes + induced fit
the receptor can indirectly trigger a secondary messenger to cause an enzyme cascade within the cell (signal transduction)
leads to a response from cell
chemical messenger breaks down, receptor left unchanged
what are the 2 main types of chemical messengers?
neurotransmitters and hormones
neurotransmitter definition
a chemical released from nerve endings which travel across nerve synapses to bind with receptors on target cells - effector/muscle cells or other nerve cells
hormone definition
a chemical released from cells/glands which travel some distance through the bloodstream to bind with receptors throughout the body
what is the difference between hormones and neurotransmitters/signals produced?
neurotransmitters/nerve signals are short lived, whereas hormones/endocrine signals tend to last a lot longer
