Week 2 Flashcards
(40 cards)
Name the types of Intercellular Communication
1) Gap Junctions
- Their functional Unit = connexin
- Permeability depends on: cAMP, H+, Ca2+ conc and Membrane voltage
2) Autocrine secretion:
- Cells release mediator which acts on same cell
3) Paracrine Secretion:
- Mediator released from one cell acts on the receptor of another cell.
4) Contact dependent Communication
5) Synaptic Transmisison
6) Endocrine Secretion
- Hormone released into blood and goes to target cell, very slow.
Describe the characteristics of Receptors
- Bifunctional
- Specific
- Saturation Kinetics
- Reversible binding
Explain what Kd is
Kd is the:
“Concentration of a Ligand at which specific binding is 50%”
smaller Kd = Receptor has greater affinity to ligand
Explain the following terms:
- Potency
- EC50
- Efficacy
Potency:
A more potent drug will cause greater biological response at lower concentrations.
EC50:
-The concentration of a Drug needed to stimulate 50% biological response.
Efficacy:
-Efficacy relates to the Maximum response of different drugs.
What is Angiotensin involved in doing? How is this useful clinically
- Angiotensin is a protein which binds to the Angiotensin Receptor and causes increase in Blood pressure.
- With the use of Angiotensin Receptor Antagonists we can reduce the Blood Pressure.
Name the two types of “Molecular Switches” which after Receptor binding can initiate a biological response
1) Phosphorylation of Proteins
2) GTP Binding Proteins
GDP-G-Proteins (Inactive) becomes GTP-G-Protein due to the action of GEF.
Then GTP-G-Protein can become inactivated by losing a P to form GDP-G-Protein (facilitated by GAP)
What are the main classifications of Receptors?
Receptors are classified into either:
1) Nuclear Receptors (found in cytsol or on DNA)
2) Plasma Membrane Receptors - these can be further subdivided into:
a) G-Protein Coupled Receptors (GPCR)
b) Ion-Channel Linked Receptor
c) Catalytic Receptor
d) Enzyme linked Receptor
Explain what GPCR are and the mechanism of their response.
- G-Proteins are Hetereotrimeric – has 1 alpha, beta, delta subunit.
- These Subunits can assemble in different combinations thus G-Proteins can relate to many type of Receptors.
How they are Activated:
1) In absence of Ligand, the Alpha subunit is binded to GDP.
2) When Ligand binds to receptor, it causes “GEF” to give GTP to Alpha thus G-Protein is activated.
3) A-GTP dissociates from Beta-Delta subunit and both these can go on and act as effectors.
Explain how G-Proteins can be inactivated.
Inactivation can occur via two ways first to inactivate other by endocytic removal of GPCR from membrane.
Inactivation:
1) GAPs converts the GTP (bound to Alpha) into GDP. (GAPs actually enhance the G-Protein GTPase activity).
2) GDP-A can join back to Beta-Delta Subunit.
Endocytic Removal:
1) binding of Hormone to GPCR will enhance “GPCR Kinase” ability to phosphorylate intracellular GPCR domain.
2) GPCR will recruit “B-Arrestins” to bind to GPCR” and inactive the GPCR and cause Endocytic removal of GPCR.
Explain the Effects of “Gs Protein”
- Gs Protein stimulates “Adenyly cyclase”
- Adenylyl cyclase will convert ATP –> cAMP.
- cAMP will activate “Protein Kinase A (PKA)”.
- PKA can phosphorylate proteins to stimulate responses.
What can activate Gs Proteins?
1) B-Adrenergic
2) ACTH-V
How is the “cAMP signal” terminated?
- cAMP is broken down by “cAMP Phosphodiesterases”.
- cAMP –> 5’AMP
- This termination can be prevented by “Caffiene” which inhibits the enyzme.
Explain the Effects of “Gi/o Proteins”.
-Gi/o proteins inhibit Adenyly Cyclase thus will lead to a decrease in the production of cAMP.
- The effects of Gi/o proteins is:
1) Decrease in cAMP
2) Opening of K+ Channels (causes Hyperpolarisation)
3) Inhibition of Ca2+ (no muscle contraction).
4) Activation of “Phospholipase A2”.
Which Receptors activate “Gi/o Proteins”?
1) Alpha-Adrenogic
2) M2/M4 Muscurine ACH
3) Opiate
What does “Phospholipase A2” do?
- This is an Enzyme which causes the release of Arachiodonic Acid.
- Arachiodonic Acid can then be acted on by either:
1) Cyclooxygenases
2) 5-Lipoxygenase
3) Epoxygenase
What is the actions of Cyclooxygenases?
They convert Arachiodonic Acid into
1) Prostaglandins
2) Prostacyclins
3) Thromboxanes
What is the actions of 5-Lipoxygenase?
5-Lipoxygenase converts Arachiodonic Acid into Leukotrienes.
-Leukotrienes participitate in Allergic/Inflammatory response (responsible for Asthma and Artheritus).
What is the Actions of Epoxygenases?
Create: HETE and EET.
HETE and EET will increase the release of Ca2+ from the ER.
Explain the effect of “Gq/11 Proteins”.
- This protein will activate “Phospholipase C”.
- Phospholipase C will convert “Phosphatidylinoistol 4,5 Biphosphate” into Diaglyerol (DAG) and Inoistol 1,4,5 Triphosphate (IP3).
Phosphatidylinoistol 4,5 Biphosphate –> DAG + IP3.
DAG: Activates PKC.
IP3: Causes the release of Ca2+ from the Endoplasmic Reticullum.
How does Calcium act as an Intracellular Messenger?
- IP3 (caused to be released by Gq/11 protein which activates Phospholipase C) can cause the release of Calcium.
- Calcium will bind to “Calmodulin” which will form a Ca2+-CaM complex.
- This complex will regulate a CaM kinase (like MICK and Phosphorylase Kinase).
MICK-
It phosphorylates Myosin Light chain so it can interact with Actin.
Phosphorylase Kinase-
This will Phosphorylate “Phosphorylase” which is important in Glucose Metabolism.
Name the Calcium Ion channels involved in Ca2+ Homeostasis.
1) IP3 Receptor.
Found on the Endoplasmic Reticulum (activated by IP3 which is created by Phospholipase C -which is activated by Gq/11 Proteins).
2) Store-Operated Channel:
When the Ca2+ conc in Endoplasmic Reticulum is low, this channel found on Plasma Membrane Opens to allow Ca2+ to enter.
3) Voltage Sensitive L-Type Channels.
Explain the Effect of “G12/13 Proteins”.
- When these are activated, A12-GTP will activate “Rho-GEF”.
- Rho-GEF converts Rho-GDP (inactive) into Rho-GTP (active).
- Rho regulates “Rho Kinase” which regulates smooth muscle contraction.
- Receptors: Thrombosin, Angiotensin II
Explain the Effect of “Gt proteins”.
- Absorption of Lights in Rods by Rhodosphin causes the activation of a G-Protein called “Transducin”.
- At-GTP will activate “cGMP diesterase.”
- This converts cGMP into GMP thus closes the “cGMP dependent Cation channel”. Thus Voltage change occurs.
How do Ion-Channel Receptors work?
-Ligand binds to a Receptor which causes a conformational change which then opens the channel.
