WEEK 9 (Enzyme-coupled receptors) Flashcards
(38 cards)
What are receptors?
- Receptors are proteins associated with cell membranes or located within the cell
- Receptors “recognise” signalling molecules by binding to them
- Binding of receptors by signalling molecules -> Cell behaviour changes
What are the three main classes of Cell-surface Receptors?
- Ion-channel-coupled receptors
- G-Protein-coupled receptors
- Enzyme-coupled receptors
What is the function of Ion-channel-coupled receptors?
They change the permeability of the plasma membrane to selected ions, altering the membrane potential and producing an electrical current
What are Transmitter-gated ion channels?
Ion-channel-coupled receptors that open in response to the binding of an extracellular signal molecule
Describe how Ion-channel-coupled receptors function in synapses
The released neurotransmitter binds to and opens the TRANSMITTER-GATED ION CHANNELS in the plasma membrane of the postsynaptic cell -> Resulting ion flows alter the MEMBRANE POTENTIAL of the postsynaptic cell -> Converts the chemical signal back into an electrical one
Where are Ion-channel-coupled and G-Protein-coupled receptors important in the body?
- ION-CHANNEL-COUPLED RECEPTORS = electrically excitable cells e.g muscle cells
- G-PROTEIN-COUPLED RECEPTORS = every cell type in the body
How do G-Protein-coupled receptors function?
G-protein-coupled receptor binds its extracellular signal molecule -> Activated receptor signals to a G protein on the opposite side of the plasma membrane -> Turns on/off an enzyme in the same membrane
What are G-proteins?
G proteins (GUANINE NUCLEOTIDE-BINDING PROTEINS) are a family of proteins that act as molecular switches inside cells and are involved in transmitting signals from a variety of stimuli outside a cell to its interior
[BOUND TO GTP = ON; BOUND TO GDP = OFF]
Describe the structure of G-Protein complexes
- Made up of alpha (α), beta (β) and gamma (γ) subunits
- Beta and gamma subunits can form a stable dimeric complex called the BETA-GAMMA COMPLEX
- The polypeptide chain traverses the membrane as seven α helices. The cytoplasmic portions of the receptor bind to a G-protein inside the cell.v
How many GPCRs are there in humans?
More than 700
What are G-protein-coupled receptors also called?
Seven-transmembrane receptors
What are the two most frequent target enzymes for G-proteins?
- ADENYLYL CYCLASE = produces the small intracellular signalling molecule CYCLIC AMP
- PHOSPHOLIPASE C = generates the small intracellular signalling molecules INOSITOL TRIPHOSPHATE and DIACYLGLYCEROL
How do G-proteins become activated?
An activated GPCR activates G proteins by promoting the α subunit to eject its GDP and pick up GTP
How is the G-protein anchored to the plasma membrane?
Both the α and γ subunits of the G protein have covalently attached lipid molecules that anchor it to the plasma membrane
How do G-proteins become inactivated?
Activated α subunit interacts with its target protein -> It activates that target protein for as long as the two remain in contact -> The G-protein α subunit switches itself off by hydrolysing its bound GTP to GDP
Describe Cholera
Cholera is caused by a bacterium that multiplies in the human intestine where it produces CHOLERA TOXIN. Condition leads to death unless steps are taken to replace lost water and ions.
MECHANISM: CHOLERA TOXIN enters the cells that line the intestine and modifies the α subunit of a G protein called Gs -> Modification prevents Gs from hydrolysing its bound GTP which locks the G protein in the active state in which it continuously stimulates ADENYLYL CYCLASE -> In intestinal cells, stimulation causes a PROLONGED and EXCESSIVE outflow of Cl- and H2O into the gut -> Catastrophic DIARRHOEA and DEHYDRATION
Describe how acetylcholine slows the heart rate
Acetylcholine binds to its GPCR on the heart cells which activates the G protein Gi -> Activated βγ complex directly opens a K+ channel in the plasma membrane which increases the cell’s permeability to K+ -> Makes the membrane harder to activate which slows the heart rate
Describe how Cyclic AMP is synthesised and degraded
SYNTHESIS = two phosphate groups from ATP is removed and joins the ‘free’ end of the remaining phosphate group to the sugar part of the AMP molecule
DEGRADATION = Breaks the new bond forming AMP
Why do G-Protein-coupled receptor reactions occur rapidly?
Because the reactions do not involve changes in gene transcription or new protein synthesis
[in contrast, responses that involve changes in gene expression are slow]
What is the difference between Cyclic AMP responses in heart and skeletal muscle tissue?
EXTRACELLULAR SIGNAL MOLECULE: Adrenaline
TARGET TISSUE: Heart
MAJOR RESPONSE: Increase in heart rate and force of contraction
EXTRACELLULAR SIGNAL MOLECULE: Adrenaline
TARGET TISSUE: Skeletal muscle
MAJOR RESPONSE: Glycogen breakdown
What is the difference between Cyclic AMP responses in fat and adrenal gland tissue?
EXTRACELLULAR SIGNAL MOLECULE: Adrenaline + Glucagon
TARGET TISSUE: Fat
MAJOR RESPONSE: Fat breakdown
EXTRACELLULAR SIGNAL MOLECULE: Adrenocorticotropic hormone (ACTH)
TARGET TISSUE: Adrenal gland
MAJOR RESPONSE: Cortisol secretion
What is the difference between Phospholipase C responses in liver and pancreas tissue?
EXTRACELLULAR SIGNAL MOLECULE: Vasopressin
TARGET TISSUE: Liver
MAJOR RESPONSE: Glycogen breakdown
EXTRACELLULAR SIGNAL MOLECULE: Acetylcholine
TARGET TISSUE: Pancreas
MAJOR RESPONSE: Secretion of amylase
What is the difference between Phospholipase C responses in smooth muscle and blood platelets?
EXTRACELLULAR SIGNAL MOLECULE: Acetylcholine
TARGET TISSUE: Smooth muscle
MAJOR RESPONSE: Contraction
EXTRACELLULAR SIGNAL MOLECULE: Thrombin
TARGET TISSUE: Blood platelets
MAJOR RESPONSE: Aggregation
Describe how Inositol Phospholipid opens Ca2+ channels
Two small messenger molecules are produced when a membrane INOSITOL PHOSPHOLIPID is hydrolysed and activates PHOSPHOLIPASE C -> INOSITOL 1,4,5-TRIPHOSPHATE (IP3) diffuses through the cytosol -> Triggers the release of Ca2+ from the ER by binding to and opening special Ca2+ channels in the ER membrane
