6 - Intro to Cell Surface Receptors Flashcards
How much of the human genome encodes receptors?
About 5%
What percentage of prescription medicines target receptors?
Approx. 40-50% - they either activate or block the action
How many Nobel Prizes have been awarded for research into cell signalling/signal transduction?
- more than 10
- most recently in 2012 to Robert Lefkowitz ad Brian Kobilka for work on the adrenaline receptor
What are hormones?
Most of the molecules that enable signalling between the cells or tissues within humans are known as hormones
How many classes of hormones?
Two - “transmembrane” AND intracellular/”nuclear” receptors
What does the term “receptor” refer to?
The term “receptor” specifically refers to macromolecular proteins that participate in intracellular communication via chemical signals, such as hormones
What does the term “macromolecular” refer to?
The term “macromolecular” refers to large structures and can be multicomponent structures, or from the structure of nuclear receptors we can see that they’re actually multiple domain large proteins
What happens upon recognition of an appropriate chemical signalling molecule (ligand)?
Receptor proteins transmit the signal into a biochemical change in the target cell
What is the important value for the strength of the signal relayed by the receptor?
Concentration of the HORMONE-RECEPTOR COMPLEX
What is the concentration of the hormone-receptor complex defined by?
- it is defined by the affinity of the hormone for the receptor, the concentration of the hormone and the concentration of the receptor
- so, if a hormone receptor complex can form at low concentrations of hormone, the affinity of the hormone for the receptor is the ability of the hormone to interact with the receptor tends to be high
What does the equivalent between receptor-bound and free hormone equal?
[H] + [R] <=> [HR] with Kd = ([HR] * [R])/ [HR]
[R] = receptor, [H] = free hormone, [HR] = receptor bound hormone.
Kd = dissociation constant (value is in units of concentration and indicates a tight binding)
What exists in equilibrium with the hormone receptor complex?
- if we have a hormoner at a particular concentration, or a hormone plus a particular concentration of a receptor
- e.g., increase the conc. of the hormone, i.e, a gland secretes more hormone that will push this equilibrium more to the right, creating more hormone receptor complex, hence more signalling in side the cell
What kind of proteins are receptors usually?
- glycoproteins or lipoproteins
- have large macromolecular protein that has sugar residues or lipid fat residues attached
How many binding sites do receptors have?
- one or more
- e.g., acetylcholine and GABA(a) receptors have two binding sites for neurotransmitters
- most receptors have one binding site e.g., insulin
What activates a receptor?
- binding of endogenous LIGAND (e.g., hormone) activates the receptor by inducing a conformational change
- one or more signals my be activated
What do cell surface receptors trigger?
Cell surface receptors can trigger changes inside the cell by virtue of their structure, in that many cell surface receptors are transmembrane proteins
What are embedded into the bilayer?
- embedded into the bilayer are proteins, many of which are receptors
- proteins can be transmembrane proteins
- they can be peripheral proteins that just interacts with one side of the membrane or another, but receptors tend to be transmembrane proteins
What makes a protein a transmembrane protein?
- they have an extracellular portion, a transmembrane segment that passes straight through the cell membrane, and an intracellular portion that can interact with enzymes inside the cell
What happens when the enzymes inside the cell are activated?
The enzymes cause changes in intracellular chemistry that is involved in transmission of signals
What are receptors often decorated with?
- receptors are often decorated with sugar residues or carbohydrate chains on the outside of the cell
- carbohydrates can be important for recognising the ligand for the receptor
What are endogenous transmitters?
These could be hormones and neurotransmitters, and these are able to interact with the ligand binding sites on particular receptors
What type of properties must receptors have?
Receptors must have properties of recognition and transduction
What does the magnitude of transmembrane signal transduction depend on?
It depends on the fraction of total membrane receptors occupied by the ligand
Why are receptors saturable?
Because of the finite number of receptors
Common features of receptors
- have properties of recognition and transduction
- saturable
- can be up- or down- regular;ated
- same hormone may have different effects of target cells
The same hormone may have different effects on target cells that have…
- different receptors for the hormone
- different signal transduction pathways
What can the hormone adrenaline increase?
The hormone adrenaline/epinephrine can increase blood flow to the major skeletal muscle, but decrease blood flow to the digestive tract
What two intracellular proteins does the beta receptor act on?
- liver cell
- smooth muscle cell
What two receptors are on smooth muscle cells?
- beta receptor
- alpha receptor
Pathway of epinephrine (hormone) on the beta receptor of a liver cell
- epinephrine interacts with the beta receptor on the liver cell
- glycogen deposits in the liver cell break down
- glucose is released from the cell
- blood glucose level increase
Pathway of epinephrine (hormone) on beta receptor of a smooth muscle cell in wall of blood vessel that supplies skeletal muscle
- epinephrine interacts with the beta receptor on smooth muscle cell
- cell relaxes
- blood vessel dilates, increasing blood flow to the skeletal muscle
Pathway of epinephrine (hormone) on alpha receptor of a smooth muscle cell in wall of blood vessel that supplies skeletal muscle
- epinephrine interacts with the alpha receptor of the smooth muscle cell
- cell contracts
- blood vessel constricts, decreased flow to intestines
