Endocrine Biochemistry Flashcards
types of signaling:
endocrine, paracrine, autocrine, and juxtacrine
give an example of each
What are the receptors involved in hydrophillic hormone signaling?
give some examples of hydrophillic hormones
can they penetrate plasma membrane
-what does the signaling molecule-receptor complex do?
GPCRs, RTKs
epi,insulin,glucagon
cant cross PM
it initiates production of second messenger molecules insdie the cell
lipophilic hormones:
examples
what does the signaling molecule-receptor complex do?
examples of DNA binding transcription factors
Summary of Lipophillic vs hydrophilic hormones
half life of hydrophilic vs lipophilic medications?
examples?
Overview of GPCR signaling
- how many subunits?
- inactive to active transformation via what protein?
- how does it go back to inactive state?
variations in GPCR signaling:
Gs, Gt, Gi, Gq
all stimulate enzymes, what are they?
know the secondary messengers
Physiological affects of the different GPCRs
- Gs via epi?
- Gs via histamine?
- Gi via epi/norepi?
- Gi via dopamine?
- Gi via AcH?
- Gt via light?
RTK Pathway:
- Extracellular domain does what?, what are the other domains?
- binding of extracellular domain to ligand causes what?
- what does dimerized receptor do?
What is the primary structure of insulin?
-chains?
linked how?
how many amino acids in each?
how is inactive insulin stored in the body?
stored as a hexamer w/zinc in center connected to polypeptides via histidines
active form is a monomer
Insulin synthesis and secretion:
Glucose upregulates what type of mRNA?
what does that mrna get translated into?
translocated where?
what is insulin released with?
Regulation of Insulin:
two phases?
what are the two different pools of insulin granules?
how does glucose actually stimulate insulin?
glucose comes into the cell via glut transporters, phosphorylated by glycolysis reactions, tca cycle, end product of tca cycle is ATP.
That atp closes a specific potassium channel in the beta pancreatic cell. causes membrane to be depolarized, which opens another channel that allows in calcium. This calcium helps release insulin into the blood.
how does insulin signaling through RTK actually work?
insulin is released in response to glucose, binds to the insulin receptor (RTK), receptor then becomes dimerized and autophosphorylated, tyrosine has a phosphate residue added to it, phosphyrlation of the receptor recruits another protein known as IRS-1, which gets phosphorylated. attracks a protein known as Grb2, which is a scaffolding protein which activates the ras pathway, which phosphorylates proteins.
this leads to increased transcription of glucokinase–> increase in glucose uptake, glycogen synthesis
RAS independent pathway: once IRS is phosphorylated, it recruits an enzyme called PI 3-kinase, which activates PKB, which phosphorylates proteins, which trigger translocation of GLUT4 movement to plasma membrane. helps uptake glucose.
RAS-dependent insulin signaling steps
RAS independent insulin signaling
Insulin resistance:
Defined
defects?
- insulin receptor
- IRS1/IRS2
- Phosphorylation abnormalities
Effects of insulin, glucagon, epi, cortisol on glucose metabolism.
- diabetes types?
- glucagon effect?
- Epinephrine effect?
- Cortisol effect?
Molecular structure of NRs
- 3 major domains
- AF1 role
- DBD binds to what?
- LBD binds to what?
Primary vs secondary response to steroid hormones
Estrogen receptor:
- two types?
- alpha vs beta
- type of transcription factors?
Mechanism of action of ER
ER is a nuclear receptor, ligand binds to receptor, causes conformational changes involve the binding of many proteins tht you dont need to know names of.
net result is promotion of HAT
more transcription occuring.
molecular mechanism of action of nuclear estrogen receptor
genomic effects:
how does tamoxifen work?
antagonist of ER
tamoxifen is metabolized by liver to CYT p450 to 4-hyroxy-tamoxifen, binds to Estrogen receptor, which promotes histone deacetylase HDAC activity
keeps dna in chromatin form
