6 - Intro to Cell Surface Receptors

Question 1

How much of the human genome encodes receptors?

Answer 1

About 5%

Question 2

What percentage of prescription medicines target receptors?

Answer 2

Approx. 40-50% - they either activate or block the action

Question 3

How many Nobel Prizes have been awarded for research into cell signalling/signal transduction?

Answer 3

• more than 10
• most recently in 2012 to Robert Lefkowitz ad Brian Kobilka for work on the adrenaline receptor

Question 4

What are hormones?

Answer 4

Most of the molecules that enable signalling between the cells or tissues within humans are known as hormones

Question 5

How many classes of hormones?

Answer 5

Two - “transmembrane” AND intracellular/”nuclear” receptors

Question 6

What does the term “receptor” refer to?

Answer 6

The term “receptor” specifically refers to macromolecular proteins that participate in intracellular communication via chemical signals, such as hormones

Question 7

What does the term “macromolecular” refer to?

Answer 7

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

Question 8

What happens upon recognition of an appropriate chemical signalling molecule (ligand)?

Answer 8

Receptor proteins transmit the signal into a biochemical change in the target cell

Question 9

What is the important value for the strength of the signal relayed by the receptor?

Answer 9

Concentration of the HORMONE-RECEPTOR COMPLEX

Question 10

What is the concentration of the hormone-receptor complex defined by?

Answer 10

• 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

Question 11

What does the equivalent between receptor-bound and free hormone equal?

Answer 11

[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)

Question 12

What exists in equilibrium with the hormone receptor complex?

Answer 12

• 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

Question 13

What kind of proteins are receptors usually?

Answer 13

• glycoproteins or lipoproteins
• have large macromolecular protein that has sugar residues or lipid fat residues attached

Question 14

How many binding sites do receptors have?

Answer 14

• 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

Question 15

What activates a receptor?

Answer 15

• binding of endogenous LIGAND (e.g., hormone) activates the receptor by inducing a conformational change
• one or more signals my be activated

Question 16

What do cell surface receptors trigger?

Answer 16

Cell surface receptors can trigger changes inside the cell by virtue of their structure, in that many cell surface receptors are transmembrane proteins

Question 17

What are embedded into the bilayer?

Answer 17

• 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

Question 18

What makes a protein a transmembrane protein?

Answer 18

• 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

Question 19

What happens when the enzymes inside the cell are activated?

Answer 19

The enzymes cause changes in intracellular chemistry that is involved in transmission of signals

Question 20

What are receptors often decorated with?

Answer 20

• 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

Question 21

What are endogenous transmitters?

Answer 21

These could be hormones and neurotransmitters, and these are able to interact with the ligand binding sites on particular receptors

Question 22

What type of properties must receptors have?

Answer 22

Receptors must have properties of recognition and transduction

Question 23

What does the magnitude of transmembrane signal transduction depend on?

Answer 23

It depends on the fraction of total membrane receptors occupied by the ligand

Question 24

Why are receptors saturable?

Answer 24

Because of the finite number of receptors

Question 25

Common features of receptors

Answer 25

1. have properties of recognition and transduction
2. saturable
3. can be up- or down- regular;ated
4. same hormone may have different effects of target cells

Question 26

The same hormone may have different effects on target cells that have…

Answer 26

• different receptors for the hormone
• different signal transduction pathways

Question 27

What can the hormone adrenaline increase?

Answer 27

The hormone adrenaline/epinephrine can increase blood flow to the major skeletal muscle, but decrease blood flow to the digestive tract

Question 28

What two intracellular proteins does the beta receptor act on?

Answer 28

• liver cell
• smooth muscle cell

Question 29

What two receptors are on smooth muscle cells?

Answer 29

• beta receptor
• alpha receptor

Question 30

Pathway of epinephrine (hormone) on the beta receptor of a liver cell

Answer 30

1. epinephrine interacts with the beta receptor on the liver cell
2. glycogen deposits in the liver cell break down
3. glucose is released from the cell
4. blood glucose level increase

Question 31

Pathway of epinephrine (hormone) on beta receptor of a smooth muscle cell in wall of blood vessel that supplies skeletal muscle

Answer 31

1. epinephrine interacts with the beta receptor on smooth muscle cell
2. cell relaxes
3. blood vessel dilates, increasing blood flow to the skeletal muscle

Question 32

Pathway of epinephrine (hormone) on alpha receptor of a smooth muscle cell in wall of blood vessel that supplies skeletal muscle

Answer 32

1. epinephrine interacts with the alpha receptor of the smooth muscle cell
2. cell contracts
3. blood vessel constricts, decreased flow to intestines