Lecture 64 Flashcards
where is the signal peptide gradient during the process of peptide/protein hormone synthesis
Endoplasmic reticulum
The final outcome between the hormone and the target cell depends on what factors?
- Hormone concentration
- Receptor number
- Affinity of hormone for receptor
- Duration of exposure to hormone
- Intracellular factors enzymes, cofactors (may help process)
Minimal concentration of hormone needed to elicit measurable response
Threshold response
what are 2 ways to express the dose-response relationship
Responsiveness (up/down) and Sensitivity (left/right)
Magnitude of response correlated with hormone concentration, what happens when concentration increases?
As concentration increases, response will increase then level off
the more receptors, what happens to the maximal response?
maximal response increases
________ is the term for a further increase in hormone will elicit no more response
Maximum response
________ may cause a decrease in responsiveness
caused by:
* decrease in number of target cells
* decrease in total receptors/cell
* decrese inconcentration of enzymes activated by hormone
the higher the affinity for a hormone, the (more/ less) likely to get a response
more
The concentration of hormone producing 50 percent of maximal response
Sensitivity
If more hormone required to get 50% response what happens to the sensitivity
decrease
The less hormone required = ________ to sensitivity
increases
Sensitivity can be changed in two ways List them.
changing number of receptors OR affinity of receptors
Decreasing sensitivity = ________ of receptors
down-regulation
Either number or affinity of receptors decreases even when __________
hormone concentrations high
Decreasing sensitivity is down-regulation of receptors causes what 3 things
- decrease synthesis of new receptors
- increase degradation of existing receptors
- inactivate receptor
what down-regulates TRH receptors in anterior pituitary
T3
Increasing sensitivity = ________ of receptors
up-regulation
Increasing sensitivity = up-regulation of receptors. What are the 2 ways this can be achieved
Either number or affinity of receptors increases
Increasing sensitivity is an up-regulation of receptors what 3 things can this lead to
increase synthesis of new receptors, decrease degradation of existing, activate receptors
example of up-regulation: ________ increases its receptors in skeletal muscle and liver
GH
Hormone is recognized and binds to a membrane receptor and this forms a __________
hormone-receptor complex
Once the Hormone-receptor complex is formed, what can happen
EITHER coupled to a signal-generating mechanism OR must act as one itself
Once the generated signal (second messenger) is formed, it can affect what
intracellular process by altering activity OR concentration of functional or structural proteins
Receptor systems are located in which of 2 locations
Either on cell membrane (faster) or within the cell (slower; cytoplasm or nucleus)
what system is this? Classified according to membrane receptor structure OR second messenger system used (Usually a rapid response (minutes))
Classic cell membrane receptor system
what system is this? Doesn’t use second messenger system, but rather an enzyme system such as kinases (Usually a rapid response (minutes))
Catalytic cell membrane receptor systems
what receptor systems have a rapid response
Catalytic and Classic
what receptor systems have a slow
Intracellular
If a higher hormone concentration is required to reach 50% of the maximal response, what has happened to hormone sensitivity?
decreased
Coupling molecules used in ALMOST ALL membrane receptor systems
G-proteins
Heterotrimeric proteins has how many subunits
3
Active or Inactive when GTP is bound
ACTIVE
Active or Inactive when GDP is bound
INACTIVE
T/F Heterotrimeric proteins can be either stimulatory or inhibitory
t
G-proteins are linked to one of two second messenger systems, what are the 2 enzymes involved?
Adenylyl cyclase & Phospholipase C
What are the secondary messengers of cell membrane receptor systems
cAMP & IP3/Ca2+/DAG
pair the enzyme with the secondary messenger:
* Adenylyl cyclase
* Phospholipase C
* cAMP
* IP3/Ca2+/DAG
- Adenylyl cyclase & cAMP
- Phospholipase C & IP3/Ca2+/DAG
Hormone binds receptor coupled by a G protein what happens next
GTP binds G protein and activates adenylyl cyclase
after GTP binds G protein and activates adenylyl cyclase, what happens
cAMP produced and activates protein kinase A
once cAMP produced and activates protein kinase A what happens next
Intracellular proteins phosphorylated by protein kinase A, causing physiologic actions
Once Intracellular proteins phosphorylated by protein kinase A, causing physiologic actions. How does the system get shut down
Phosphodiesterase degrades cAMP, shutting down system
List some examples of hormones using the adenylyl cyclase system
- FSH
- LH
- ADH
- TSH
- Calcitonin
what is the job of a kinase
phosphorylate
Phospholipase C system: Hormone binds receptor coupled by a G protein what happens next
GTP binds G protein and activates phospholipase C
Phospholipase C system: once GTP binds G protein and activates phospholipase C what happens next
Phospholipase C liberates diacylglycerol (DAG) and IP3 from PIP2
Phospholipase C system After Phospholipase C liberates diacylglycerol (DAG) and IP3 from PIP2 what happens next
IP3 causes Ca2+ release from ER or SR stores
Phospholipase C system: After IP3 causes Ca2+ release from ER or SR stores what happens
Ca2+ and DAG activate protein kinase C, which phosphorylates proteins
List some hormones using the phospholipase C system
- GnRH
- Angiotensin 2
- ADH
- Oxytocine
Catalytic receptors on cell surface associated with enzymes on ________ side
intracellular side
Guanylyl cyclase enzyme: GTP to cGMP to what to phosphorylates proteins
cGMP-dependent kinase
Atrial natriuretic peptide (ANP) and nitric oxide (NO) use what enzyme system
Guanylyl cyclase enzyme
which hormone receptor is Protein kinase A associated with
Adenylyl cyclase system
which hormone receptor is Protein kinase C associated with
Phospholipase C system
which hormone receptor is cGMP kinase associated with
Guanylyl cyclase enzyme system
Serine/threonine kinase enzymes: Use either protein kinase A or C, as well as ________ and mitogen-activated protein kinases (MAPK) tophosphorylate serine and threonine
Ca2+-calmodulin-dependent protein kinase (CaMK)
Use either protein kinase A or C, aswell as Ca2+-calmodulin-dependentprotein kinase (CaMK) and mitogen-activated protein kinases (MAPK) to phosphorylate __________
serine and threonine
Tyrosine kinase activity ________ the receptor itself
within
Receptor tyrosine kinases has ________ domains
3
what are the 3 domains of receptor tyrosine kinases
- Extracellular domain for binding
- Transmembrane domain
- Intracellular domain- where tyrosine kinase activity occurs
Receptor tyrosine kinases: When hormone binds, intracellular portion of receptor will _________
phosphorylates itself
receptor tyrosine kinases: There is a monomer type and a _______ type
dimer
Receptor tyrosine kinases: Describe a Monomer type
Receptor us going to dimerize after hormone binds- tyrosine kinase activated and phosphorylate tyrosine on itself
Receptor tyrosine kinases: Describe a Dimer type
Receptor is already a dimer such as insulin or IGF
Tyrosine kinase-associated receptors: Associate with other proteins that have tyrosine kinase activity such as ________ family of receptors
Janus kinase family (JAK)
Catalytic receptor systems - tyrosine kinases: T/F Intracellular portion cannot phosphorylate itself
t
Steroid hormones utilize what receptor system
Intracellular receptor systems
Intracellular receptor system uses either _____ or _____ receptors
Use either cytosolic or nuclear receptors
Steroids are lipid soluble meaning they can
diffuse across the membrane (from cholesterol)
Intracellular receptor systems: Initiate DNA transcription and synthesis of new proteinsm, is this process slow or fast
SLOW, VERY SLOW
DNA transcription and synthesis of new proteins: Steroid hormone diffuses across membrane and binds receptor in cytosol or nucleus, what happens next
- Receptor undergoes conformational change
- complex dimerizes and binds to steroid-responsive elements (SREs)
what does SRE stand for? What is it?
steroid-responsive elements (SREs); Specific DNA sequences in target genes
DNA transcription and synthesis of new proteins: After receptor undergoes conformational change, complex dimerizes and binds to steroid-responsive elements (SREs) what happens
- Complex is now a transcription factor
- mRNA transcribed
- translation occurs
- new proteins
- physiologic action
List some hormones that utilize intracellular receptor systems
- Sex hormones
- Aldosterone
- Vitamin D