Cell Physiology Lecture 3

Question 1

Chemical Messengers may be __________

Answer 1

lipid soluble or lipid insoluble

Question 2

Chemical Messengers are a form of:

Answer 2

Communication between cells

Question 3

What are chemical messengers used for?

Answer 3

The process of turning a signal into a functional response (signal transduction). It is the sequence of the binding of a messenger to a receptor, and the production of a cellular response.

Question 4

4 Properties of receptors

Answer 4

1. Receptors have specific binding sites for a specific messenger
2. Receptors show saturation in that they have a defined number of binding sites for a messenger (only 1 or 2 binding sites for a messenger)
3. Receptors bind different messengers with different affinities. (meaning how strong a receptor and messenger bind, high affinity means strong, low means weak. (If weak you would require higher concentrations to bind)
4. Receptors may be found on the cell membrane or intracellularly, in the cytosol or nucleus.

Question 5

Intracellular Receptors

Answer 5

Receptors that are found inside the cell, in the cytoplasm or nucleus

Question 6

_____________ diffuse across the plasma membrane and bind to intracellular receptors

Answer 6

Lipid-soluble chemical messengers

Question 7

Example of chemical messengers that bind to intracellular receptors:

Answer 7

steroid hormones
(hormones derived from cholesterol)

Question 8

Intracellular Receptor steps

Answer 8

-Transcription factors alter the rate of transcription of mRNA in the nucleus by binding to a response element

-A response element is a specific sequence of DNA naer the beginning of a gene. By binding to the response element, a chemical messenger can alter the rate of transcription of a gene which will alter the rate of translation of the mRNA into a preotin (as each gene contains the instructions for producing a specific protein)

-Transcription factos alter the rate of protein synthesis

Question 9

Chemical messengers that are water-soluble (hydrophilic, lipid-insoluable) can not ____________

Answer 9

Diffuse across the hydrophobic core of the plasma mebrane, so they bind to receptors on the extracellular surface of the plasma membrane instead

Question 10

Examples of soluble chemical messengers

Answer 10

-Peptides, Protein hormones

Question 11

3 Examples of membrane-bound receptors

Answer 11

-Channel-linked receptors

-Enzyme-linked receptors

-G Protein-linked receptors

Question 12

First Messenger

Answer 12

Extracellular chemical messenger that binds to a specific membrane bound receptor

Question 13

Second Messenger

Answer 13

a substance that enters or is generated in the cytoplasm of a cell following the binding of the first messenger to its receptor

Question 14

Protein Kinase

Answer 14

an enzyme that phosphorylates another protein, (adding phosphate group to the protein). By adding phosphate groups to a protein, a protein kinase alters the activity of another protein

Question 15

Ligand-Gated Ion Channel

Answer 15

Ligand-gated ion channels are a type of receptor found in the cell membrane that act like gates for ions (charged particles like sodium, potassium, or calcium) to enter or leave the cell. These channels only open when a specific molecule, called a ligand (often a neurotransmitter or hormone), binds to them.

Question 16

Steps of Signal Transduction in membrane bound receptors that are Ligand-gated ion channels

Answer 16

1. A first messenger binds to binding sites on the receptor
2. An ion channel in the receptor protein opens
3. Ions move through the channel. As the ions have a charge, they alter the electrical properties of the cell and produce a response.

Question 17

Is Signal Transduction in membrane bound receptors that are Ligand-gated ion channels a slow or fast process?

Answer 17

fast process as the receptor and ion channel are a single protein

Question 18

membrane bound receptors that are Ligand-gated ion channels may be ________

Answer 18

calcium channels, as calcium has many roles in the cell

Question 19

A membrane-bound receptor that functions as an enzyme

Answer 19

a receptor (a protein) has a receptor component with binding sites for a chemical messenger and intrinsic enzyme activity (intrinsic = within the receptor protein

Question 20

What are receptors that function as enzymes also called?

Answer 20

Also called receptor tyrosine kinases: the enzyme part of the receptor is a kinase that phosphorylates tyrosine amino acid residues (ie. adds phosphates to tyrosine amino acid residues)

Question 21

The tyrosine kinase part of an enzyme receptor ___________

Answer 21

autophosphorylates or phosphorylates tyrosine amino acid residues on the receptor (auto = self)

Question 22

Phosphotyrosines

Answer 22

Phosphorolated tyrosines

Question 23

The phosphorylated tyrosines (phosphotyrosines) on the enzyme receptor act as

Answer 23

docking sites for proteins in the cytoplasm of the cell

Question 24

Once a protein binds to the phosphotyrosines on an enzyme receptor ___________

Answer 24

it is activated by phosphorylation, and will bind to other proteins in the cell to eventually produce a response

Question 25

G-Protein linked receptor:

Answer 25

membrane-bound receptor that binds extracellular chemical
messengers

Question 26

Where are G-proteins found?

Answer 26

at the cytosolic surface of the plasma membrane

Question 27

Why are G-Proteins called G-proteins?

Answer 27

because they bind guanosine nucleotides (GDP or GTP

Question 28

G-proteins are made from:

Answer 28

3 subunits called alpha, beta and gamma

Question 29

G-Proteins function as _______

Answer 29

a link between the receptor in the plasma membrane, and an effector protein (ion channel or enzyme)

Question 30

Both the _____________ interact with the G-Protein

Answer 30

Receptor and effector proteins

Question 31

What part of the G-Protein binds to GTP or GDP?

Answer 31

The alpha subunit, not the beta or gamma subunit

Question 32

Alpha subunit of G-Protein function:

Answer 32

binds the guanosine nucleotides GDP and GTP

Question 33

Alpha subunit of G-Protein function when inactive

Answer 33

when inactive binds GDP

Question 34

Alpha subunit of G-Protein function when active

Answer 34

which active binds GTP

Question 35

What does the binding of an extracellular first-messenger to a G-protein link receptor cause in the receptor?

Answer 35

It causes a conformational change in the receptor, decreasing the affinity of the alpha subunit for GDP, and increasing the affinity for GTP; The alpha subunit releases GDP and bind GTP

Question 36

G-Protein linked receptor steps

Answer 36

Binding of an extracellular first messenger to a membrane-bound receptor causes a
conformational change in that receptor, altering the affinity of the alpha subunit of the G-protein for GDP

The affinity of the alpha subunit for GDP decreases and the affinity for GTP increases; the alpha subunit releases GDP and binds GTP

The G protein will now dissociate from the receptor and the GTP-bound alpha subunit is activated and separates from the beta and gamma subunits

The activated alpha subunit moves to its target protein in the membrane, called the effector protein
.
Effector protein is either an enzyme or an ion channel

 The GTP-bound alpha subunit will alter the activity of this effector protein to
produce a response in the cell

o The activated alpha subunit hydrolyzes, or breaks down, the GTP to GDP and inorganic
phosphate, returning itself to the inactive state in which it is bound to GDP.

The alpha subunit recombines with the beta and gamma units, which anchor the alpha in the membrane.

o The G-protein with the 3 subunits (alpha, beta and gamma) then recombines with the receptor

Question 37

How does binding of a first messenger alter the activity of an effector ion channel? (Actions of G-Proteins on ion channels)

Answer 37

1. Binding of first messenger to receptor causes conformational change in receptor
2. Affinity of α-subunit for GTP increases; GDP dissociates, GTP binds
3. GTP-bound α-subunit dissociates from β and γ; moves to ion channel
4. Ion channel opens or closes (depending on state of channel prior to binding of GTP-bound α-subunit), alters flow of ions across membrane

Question 38

How does binding of a first messenger alter the activity of an effector enzyme (Action of G-Proteins on enzymes)

Answer 38

1. Binding of first messenger to receptor causes a conformational change in the receptor
2. Affinity of a alpha-subunit for GTP increases, GDP dissociates, GTP Bind
3. GTP-bound α-subunit dissociates from β and γ; moves to enzyme
4. There are different types of G-proteins:
   ( If the G-protein is a Gs protein, it stimulates or activates the enzyme (S= stimulatory); if the G-protein is a Gi protein, it inhibits the enzyme (I= inhibitory)
5. Altering the activity of the enzyme alters the production of a second messenger by the enzyme in the cytosol

Question 39

_________________ is the most common second messenger system found in
the cells in our body

Answer 39

cAMP Second Messenger System

Question 40

cAMP =

Answer 40

a second messenger

Question 41

Steps involved int the production of cAMP:

Answer 41

1.Binding of a first messenger to a receptor causes a conformational change in the
receptor. This increases the affinity of the alpha subunit for GTP; GTP binds after
the release of GDP.

2.The activated alpha subunit of the Gs protein separates from the beta and
gamma subunits and moves to and binds to adenylyl cyclase, activating it.

• Adenylyl cyclase is a membrane-bound enzyme
  -A stimulatory G protein or GS stimulates or activates adenylyl cyclase

3.The catalytic site of adenylyl cyclase is located on the cytoplasmic surface of the plasma membrane; adenylyl cyclase catalyzes the conversion of cytosolic ATP molecules into cyclic AMP.

4.Cyclic AMP acts as a second messenger and diffuses through the cytoplasm

5.cAMP binds to and activates protein kinase A (PKA), which is also called cyclic-
AMP-dependent protein kinase. (PKA requires cAMP to activate it)

6. Activated PKA catalyzes the phosphorylation of proteins in the cell by transferring a phosphate group from ATP to cellular proteins
7. Once these cellular proteins have been phosphorylated, their activity is altered, resulting in a cellular response

Question 42

Calcium may act as a ________

Answer 42

Second messenger in cells

Question 43

Calcium is normally found in low _________-

Answer 43

concentrations in the cytoplasm

Question 44

Steps of Calcium as a Second Messenger:

Answer 44

1.the extracellular fluid following the binding of a first messenger to a receptor

(The receptor may be a receptor that is a ligand-gated ion channel, in which case
the intrinsic ion channel opens and allows calcium to move into the cell. The receptor may be a G-protein linked receptor, which will open a calcium channel in the membrane. With either receptor, calcium enters the cell and its concentration increases in the cytoplasm.)

2. The increase in calcium levels in the cytoplasm is not enough to produce a response in the cell; calcium that has entered the cytoplasm from the ECF will bind to receptors on an organelle called endoplasmic reticulum (the ER may store calcium; it has a high concentration of calcium). Binding of calcium to receptors on the ER causes calcium to be released from the ER, further increasing levels in the cell; this is called calcium- induced calcium release as calcium entering the cell from the ECF causes its own release from the ER into the cytoplasm.
3. Calcium now acts as a second messenger
4. Calcium activates calmodulin, a cytosolic protein that is normally found inactive in the
   cell; calmodulin requires calcium to activate it
5. Active calmodulin activates a calmodulin-dependent protein kinase
6. The protein kinase phosphorylates proteins in the cell, producing a response