Hormone Signaling Pathways 2/1 Zaidi Flashcards
What are examples of hydrophilic molecules?
What kind of receptors do they use?
Located where?
Histamine, serotonin, Insulin, glucagon, ACh, etc
GPCRs and RTKs
Cell surface
What are some lipophilic signaling molecules?
What receptors do they use?
Steroid hormones, thyroxine, retinoids
Within the cytoplasm and nucleus
When the cytoplasmic receptors are in inactive form, what are they complexed with?
When translocating to the nucleus, what does it bind?
HSP 90
Specific DNA sequence HRE
Which medications have a longer half life aka last longer?
Lipophilic meds
What are the subunits of GPCRs?
Alpha, beta, gamma
What is used to activate the inactive trimeric G protein?
GEF
What is used to remove the GTP from the active G protein?
GAP
What triggers the Gt pathway?
What does it activate?
Light
cGMP
What are the physiological responses of Epinephrine?
Relax bronchial and intestinal smooth m.
Contracts heart m.
INC breakdown of TAGs, glycogen
INC glycolysis in muscle
What pathway is used when the Beta-adrenergic Epi receptor is activated?
Gs
What pathway is used when the alpha-2-adrenergic Epi receptor is activated?
Gi
What connects the A chain to the B chain of insulin?
How many a.a. Is the A chain and B chain?
Disulfide bridges, additional one in A chain
A-21
B-30
What phospohorylates CREB in the cytosol of epinephrine signaling?
What happens next?
PKA
Translocates to nucleus and activates CRE which up regulates gene expression
What pathway is used when the alpha-1-adrenergic Epi receptor is activated?
Gq
How is the inactive form of insulin stored?
Active form?
Hexameter
Monomer
How are the granules of insulin divided?
readily releasable pool (RRP) which accounts for the 1st release
Reserve pool (95%) responsible for the 2nd phase of insulin secretion, must first undergo mobilization
What kind of receptor does insulin use?
What specific receptor?
Then what happens?
RTK
IRS-1
Receptor is phosphorylated
Describe the RAS dependent pathway
IRS-1 -> GRB-2 -> RAS -> alters gene transcription (INC glucokinase) -> INC glucose uptake and glycogen synthesis
Describe the RAS independent pathway
IRS-1 -> PI 3-kinase -> PKB -> alterations in protein and enzyme activity (INC GLUT4) -> INC glucose uptake and glycogen synthesis
What domain binds the PO4’ed IRS-1 receptor?
SH2
Where is insulin located/where does it act?
Muscle, adipocytes, liver
How else can PKB promote glycogen synthesis?
By phosphorylating and inhibiting GSK-3
INC phosphorylation of what contributes to insulin resistance?
What is inhibited?
Serine via Ser/Thr kinase instead of Tyr
IRS inhibited
What are Ser/Thr kinases activated?
FFA
DAG
Ceramics
Inflammatory molecules
DIC F
Under conditions of glucose deficiency what releases glucagon?
What does this do?
Pancreas
INC blood sugar via glycogen breakdown and inhibition of glycogen synthesis
What also stimulates breakdown of glycogen via glucagon secretion?
Epinephrine
What stimulates gluconeogensis once glycogen stores are depleted?
Cortisol
What are the 3 major domains of Nuclear Receptors?
AF1
DBD
LBD
Which domain is highly conserved and binds to HRE?
DBD
Which binding domain is independent of ligand binding and con modify the confirmation of the entire receptor?
AF1
Which receptor binds to various molecules which regulates ligand-dependent activation of receptor?
LBD
where is ER alpha expressed?
Female reproductive tract Mammary gland Hypothalamus Endothelial cells Vascular smooth m.
FEM HV
Where is ER beta expressed?
Prostate and ovaries Lung Brain Bone Vasculature
BBP LV
What is an antagonist to the ER that inactivates the transcription?
What is recruited to the complex that prevents interaction with the GTA via tightening of chromatin??
Tamoxifen
HDAC1
What are some non-genomic ERs located?
In the PM in caveolae (cholesterol domains)
What are hormone synthesized and secreted by?
Endocrine cells
