Cell Physiology Lecture 3 Flashcards
Chemical Messengers may be __________
lipid soluble or lipid insoluble
Chemical Messengers are a form of:
Communication between cells
What are chemical messengers used for?
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.
4 Properties of receptors
- Receptors have specific binding sites for a specific messenger
- 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)
- 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)
- Receptors may be found on the cell membrane or intracellularly, in the cytosol or nucleus.
Intracellular Receptors
Receptors that are found inside the cell, in the cytoplasm or nucleus
_____________ diffuse across the plasma membrane and bind to intracellular receptors
Lipid-soluble chemical messengers
Example of chemical messengers that bind to intracellular receptors:
steroid hormones
(hormones derived from cholesterol)
Intracellular Receptor steps
-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
Chemical messengers that are water-soluble (hydrophilic, lipid-insoluable) can not ____________
Diffuse across the hydrophobic core of the plasma mebrane, so they bind to receptors on the extracellular surface of the plasma membrane instead
Examples of soluble chemical messengers
-Peptides, Protein hormones
3 Examples of membrane-bound receptors
-Channel-linked receptors
-Enzyme-linked receptors
-G Protein-linked receptors
First Messenger
Extracellular chemical messenger that binds to a specific membrane bound receptor
Second Messenger
a substance that enters or is generated in the cytoplasm of a cell following the binding of the first messenger to its receptor
Protein Kinase
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
Ligand-Gated Ion Channel
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.
Steps of Signal Transduction in membrane bound receptors that are Ligand-gated ion channels
- A first messenger binds to binding sites on the receptor
- An ion channel in the receptor protein opens
- Ions move through the channel. As the ions have a charge, they alter the electrical properties of the cell and produce a response.
Is Signal Transduction in membrane bound receptors that are Ligand-gated ion channels a slow or fast process?
fast process as the receptor and ion channel are a single protein
membrane bound receptors that are Ligand-gated ion channels may be ________
calcium channels, as calcium has many roles in the cell
A membrane-bound receptor that functions as an enzyme
a receptor (a protein) has a receptor component with binding sites for a chemical messenger and intrinsic enzyme activity (intrinsic = within the receptor protein
What are receptors that function as enzymes also called?
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)
The tyrosine kinase part of an enzyme receptor ___________
autophosphorylates or phosphorylates tyrosine amino acid residues on the receptor (auto = self)
Phosphotyrosines
Phosphorolated tyrosines
The phosphorylated tyrosines (phosphotyrosines) on the enzyme receptor act as
docking sites for proteins in the cytoplasm of the cell
Once a protein binds to the phosphotyrosines on an enzyme receptor ___________
it is activated by phosphorylation, and will bind to other proteins in the cell to eventually produce a response
G-Protein linked receptor:
membrane-bound receptor that binds extracellular chemical
messengers
Where are G-proteins found?
at the cytosolic surface of the plasma membrane
Why are G-Proteins called G-proteins?
because they bind guanosine nucleotides (GDP or GTP
G-proteins are made from:
3 subunits called alpha, beta and gamma
G-Proteins function as _______
a link between the receptor in the plasma membrane, and an effector protein (ion channel or enzyme)
Both the _____________ interact with the G-Protein
Receptor and effector proteins
What part of the G-Protein binds to GTP or GDP?
The alpha subunit, not the beta or gamma subunit
Alpha subunit of G-Protein function:
binds the guanosine nucleotides GDP and GTP
Alpha subunit of G-Protein function when inactive
when inactive binds GDP
Alpha subunit of G-Protein function when active
which active binds GTP
What does the binding of an extracellular first-messenger to a G-protein link receptor cause in the receptor?
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
G-Protein linked receptor steps
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
How does binding of a first messenger alter the activity of an effector ion channel? (Actions of G-Proteins on ion channels)
- Binding of first messenger to receptor causes conformational change in receptor
- Affinity of α-subunit for GTP increases; GDP dissociates, GTP binds
- GTP-bound α-subunit dissociates from β and γ; moves to ion channel
- Ion channel opens or closes (depending on state of channel prior to binding of GTP-bound α-subunit), alters flow of ions across membrane
How does binding of a first messenger alter the activity of an effector enzyme (Action of G-Proteins on enzymes)
- Binding of first messenger to receptor causes a conformational change in the receptor
- Affinity of a alpha-subunit for GTP increases, GDP dissociates, GTP Bind
- GTP-bound α-subunit dissociates from β and γ; moves to enzyme
- 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) - Altering the activity of the enzyme alters the production of a second messenger by the enzyme in the cytosol
_________________ is the most common second messenger system found in
the cells in our body
cAMP Second Messenger System
cAMP =
a second messenger
Steps involved int the production of cAMP:
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)
- Activated PKA catalyzes the phosphorylation of proteins in the cell by transferring a phosphate group from ATP to cellular proteins
- Once these cellular proteins have been phosphorylated, their activity is altered, resulting in a cellular response
Calcium may act as a ________
Second messenger in cells
Calcium is normally found in low _________-
concentrations in the cytoplasm
Steps of Calcium as a Second Messenger:
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.)
- 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.
- Calcium now acts as a second messenger
- Calcium activates calmodulin, a cytosolic protein that is normally found inactive in the
cell; calmodulin requires calcium to activate it - Active calmodulin activates a calmodulin-dependent protein kinase
- The protein kinase phosphorylates proteins in the cell, producing a response
