PHAR232 - Weeks 3 & 4 Flashcards
Do heart beta receptors decrease with age?
Yes
What are the 2 primary groups of receptors?
- Ionotropic receptors
- Metabotropic receptors
Are ionotropic receptors fast or slow?
Fast (milliseconds)
Name 3 examples of ligand-gated ion channels (ionotropic)
- Nicotinic ACh receptor
- GABA-A receptor
- NMDA glutamate receptor
How many ACh ions are required to bind to open up a nicotinic ACh receptor?
2
What nutritional compound is bound to stabilize NMDA glutamate receptors and must leave before glutamate can bind?
MG2+
What are the 2 main positive ions for stimulatory influx?
Na+
Ca2+
(depolarisation)
What are the key INHIBITORY ions for ligand-gated ion channels?
K+ = (positive efflux) e.g. hyperpolarism
Cl- (negative influx)
Making the cell more negative
What is the GOAL of the ligand-gated ion channels?
To change membrane potential
- negative (hyperpolarise) or positive (depolarise)
What are some examples of G-protein coupled receptors?
0 Noradrenaline,
- Serotonin
- Muscarinic ACh
- Opioid
- GABA-B
- Histamine
- Prostaglandins
How many transmembrane domains do a GPCR have?
7
What is a newer GPRC type?
Protease-activated receptors (PARs)
List Protease-activated receptors (PARs) attributes
- Tehtered ligand
- Looks like GPCR
- Interacts with GPCR
- REGULATION VIA PHOSPHORYLATION
- 1 use only
- AGONIST IS PART OF THE RECEPTOR
- Implicated as a ‘warning system’ for diseases
What is the newer GPCR that is activated by H+ ions?
proton-sensing
What’s the name of GPCR that are activated by specific lipids? e.g. lysophosphatidylcholine
lysolipid-sensitive GPCR
- associated with cancers
- Inflammation
- Apoptosis
What is a GPCR that is highly associated with the parathyroid hormone?
calcium-sensing receptors
What are key physical aspects of the GPCR?
- Heterotrimeric: 3 individual proteins in combination (alpha, beta, gamma)
- ## 7 transmembraine domains
When speaking of a beta subtype - are we talking about 1. the ion channels or 2. the G-protein subtype?
- the g-protein subtype
What are key things that define an alpha subunit?
- GTPases
- THEY ARE AN ENZYME
- alpha subunit a rest has GFP bound to it
- at rest unit = alpha + beta + gamma
- Activation = enzyme receptor changes shape for interaction
Alpha subunit shape change causes ________ to be DROPPED and _______ to be taken up?
GDP = DROPPED
GTP = INTAKE - active
What ACTIVATES the alpha subunit?
alpha subunit + GTP = active subunit
How many gamma subunits have been encoded?
12
Learn and DRAW OUT
MUST KNOW THIS PROCESS - DRAW IT OUT - LEARN
WRITE OUT EXACTLY G PROTEIN SIGNALLING CASCADE
Is beta-gamma often found connected as a subunit?
Yes
What do GTPase-activating proteins (GAPS) do?
Bind to alpha subunits or small GTPases to increase rate of cleavage of phosphate from GTP
- E.G. CUT OFF THE GTP PHOSPHATE AS FAST AS POSSIBLE
= INACTIVATION OF SUBUNIT
What is RAS known as?
A low molecular weight GTPase (alpha)
If you have an increase in GTPase-activating proteins, you shorten alpha subunit time (action)
§
What is the job of GAPs aka GTPase-activating proteins?
Cut off the alpha phosphate as fast as possible
GTP = effect
GDP = stops working
= INACTIVATION OF SUBUNIT
What do GEFs do?
ACTIVATE G-proteins or small GTPases by PROMOTING EXCHANGE OF GDP FOR GTP
WHat is the particular GEF identified in the development of Alzheimer’s disease?
Presenilin
What are the differences between GAPs and GEFs?
GAPS:
- Shortens alpha subunit activity = SHORTENS EFFECT OF RECEPTOR ACTIVATION
= DISCOURAGES GPCR SIGNALLING
= ‘OFF’
GEFs:
- ENCOURAGES activation of GPCR
- INCREASES receptor activation
= ‘ON’
What does GDIs stand for?
Guanine Nucleotide Dissociation Inhibitors (GDIs)
What do GDI’s do?
PREVENT ACTIVATION of G-proteins or small GTPases
- Stabilises proteins in GDP-bound form
How many GDI’s have been identified?
10
What is protein kinase A highly dependent on?
(cAMP) dependent protein kinase
What does a kinase do?
Puts a phosphate (Pi) onto a protein from ATP
What is protein kinase A (PKA) controlled by?
cAMP
What is protein kinase G controlled by?
cGMP
What is protein kinase C (PKC) controlled by?
DAG
What was the original G-protein found?
Adenylate cyclase
What is the key responsibility of adenylate cyclase (AdCy)?
- Large enzyme responsible for conversion of ATP INTO cAMP!
How many MEMBRANE-associated enzymes is Adenylate cyclase associated with?
9
How many cytoplasmic enzymes is adenylate cyclase associated with?
1
Is phospholipase C a catalytic enzyme?
Yes
What 2 signalling molecules does phospholipase C make?
- Inositol trisphosphate (IP3)
- Diacylglycerol (DAG)
What was Ip3 primarily do?
Activated IP3 receptors on endoplasmic reticulum to promote Ca2+ release
What does diacylglycerol (DAG) primarily do?
Activates protein kinase C (PKC)
What 2 molecules does phospholipase C use to produce IP3 and DAG?
- Phosphatidylinositol
- Bisphosphate
REVIEW AND LEARN - WRITE IT OUT
