Part Four: Second Messengers

Question 1

Second messengers

Answer 1

are small intracellular molecules that transmit and amplify the initial signal from the ligand activated receptor
ideal properties: Rapid generation, small size and ability to readily diffuse, rapid removal from system

Question 2

Classifications

Answer 2

Ions,
Water soluble molecules
membrane associated molecules

Question 3

Calcium 2nd messenger

Answer 3

used by cells to regulate many diverse activities:muscle contraction, secretion, metabolism, neuronal excitability etc

• simply moved around cell, not made nor destroyed
• {Ca] in the particular compartment of the cell is the signal detected by the next member in the signaling cascade

Question 4

[Ca] high vs low

Answer 4

cell activation depends on the balance bw calcium-off and calcium-on mechansims

low cytoplasmic [Ca] (10^-7M) - cells remain quiescent
Increases in [Ca ] - sensors detect rise and activate specific response

Question 5

Ca removal (off mechanisms

Answer 5

-pump Ca from cell or back into internal stores (hindered by large electrochemical gradient)

-Plasma membrane protein Ca pumps: Na-Ca exchanger (NCX) antiporter (low affinity, high transport rate)
Ca-ATPase (PMCA) (high affinity, low transport rate)

-Intracellular Ca pumps: Sarco/endoplasmic reticulum Ca-ATPase (SERCA)

Question 6

Calcium addition (on mechanisms)

Answer 6

add from extracellular sources and internal stores–favored by large electrochem gradient

• Plasma membrane channels:
• Ligand gated ion channel receptors (ccation selective) - nerve/smooth muscle
• Voltage Gated channels–AP responsive, nerve, muscle, some endocrine

Intracellular calcium channels:
1,4,5-Inositol triphosphate receptors (IP3R)-universal
Ryanodine receptors (RyR)- skeletal and cardiac
(both are CALCIUM induced CALCIUM release)

Question 7

Calcium molecular sensors (action)

Answer 7

Calcium binding proteins act as molecular sensors to detect changes in Ca concentration
-Activated sensors stimulate the cascade of downstream proteins to regulate specific functions

-2 major sensors: Tropinin C and Calmodulin

Question 8

Tropinin C

Answer 8

TnC
is restricted to skeletal and cardiac muscle
-regulate contraction by controlling actin-myosin interactin

Question 9

Calmodulin

Answer 9

CaM
found in all cells
mediates many regulatory pathways
-Serine/threonine kinases
-phosphatases
-PMCA pumps
-Adenylate cyclases

Question 10

Ca-CaM dependent protein Kinase

Answer 10

CaM Kinase II

• Ca binds to CaM, making complex,
• this complex binds to inhibitory domain at C terminal of inactive protein
• becomes activated,
• ATP autophosphorylation makes new complex fully active, Ca-CaM complex dissociates
• leaves 50-80% active, then phosphatase inactivates it by removing phosphate

Question 11

Cyclic nucleotides

Answer 11

cAMP

cGMP

Question 12

cAMP cytoplasmic source

Answer 12

Adenosine Triphosphate

Question 13

cAMP effector enzyme

Answer 13

adenylate cyclase at plasma membrane, removes pyrophosphate from ATP

Question 14

cAMP enzyme activation

Answer 14

G protein coupled receptors (alpha and beta-gamma subunits)

Question 15

cAMP function

Answer 15

activators of PKA

Question 16

cAMP control

Answer 16

regulation of cell metabolism

long lasting changes in gene expression (metabolic enzymes, polypeptide hormones, ion transport proteins)

Question 17

cAMP action

Answer 17

ligand binds to G protein and sends alpha subunit w/ bound GTP binds to adenylate cyclase, which w/ ATP produces cAMP, which binds to receptors
Regulation: Depending on which G protein is activated can gave +/- effect

Question 18

Cholera toxin

Answer 18

increases PKA activation
sustained opening of Cl channels
excessive loss of water and Na into intestine (dehydration and shock)

Question 19

Pertussis toxin

Answer 19

Increased PKA activation
altered hormonal activities
HIgh insulin; low glucose (seizures)
High histamine; low pressure (shock)

Question 20

cAMP termination

Answer 20

cAMP phosphodiesterase w/ h20 makes 5’-AMP

Question 21

cGMP cytoplasmic source

Answer 21

GTP

Question 22

cGMP effector enzyme

Answer 22

soluble guanylate cyclase-generates cGMP from GTP

membrane associated guanylate cyclase (when NO is present)

Question 23

cGMP enzyme activation

Answer 23

gaseous NO

enzyme linked receptors

Question 24

cGMP function

Answer 24

activator of cGMP-dependent kinase (PKG) and cGMP dependent phosphodiesterase
Regulator of cGMPgated ion channels

Question 25

cGMP control

Answer 25

regulation of muscle and nonmuscle contractility, visual signalling, blood volume homeostasis

Question 26

cGMP action

Answer 26

both effector enzymes bind GTP, and produce cGMP, which activates PKG phosph of enzymes

Question 27

cGMP termination

Answer 27

cGMP Phosphodiesterase w/ h2o creates 5’GMP

Question 28

Phospholipid derivatives

Answer 28

membrane sources
-PI (phosphotidylinositol), PIP (phosphotidylinositol-4-phosphates), PIP2 phosphotidylinositol-4,5-bisphosphates)
-PC-phosphatidylcholine
PE-phosphatidylethanolamine

Question 29

Phospholipid derivatives

Answer 29

IP3-1,4,4 inositol trisphosphate
DAG- diaglycerol
AA- arachidonic acid
PIP3- phosphatidylinositol-3,4,5 trisphosphate