Flashcards in Intro Molecular Endocrinology Deck (32)
5 mechanisms for intercellular communication
travels to the blood to far away organ/tissue
hormone does not travel in the blood and can act on itself or the same cell type
hormone does not travel in the blood and only goes short distances to act on different cell type
the hormone is membrane bound and therefore the target cell and the signaling cell must make direct contact
3 structural classes of hormones
1. peptide (including glycoprotein)
2. steroid (all derived from cholesterol except retnoic acid)
3. amines (tyrosine derived)
Describe peptide hormone synthesis
Peptides have at the amino terminal a signal sequence that signals for the ribosome to move to the ER. The first peptide made is the pre-prohormone (not active) and this is what contains the signal sequence. Once at the ER, the peptide is synthesized into the lumen of the ER where the signal sequence gets cleaved by a peptidase leaving a pro hormone (still not active). Each prohormone has a specific peptidase that cleaves the pro domain off leaving an active hormone. Hormone is packaged into vesicles (golgi does the packaging) and is stored there until the cell receives a signal causing the vesicles to fuse with the plasma membrane causing them to fuse with plasma membrane via exocytosis.
Where are the steroid hormones derived from? Include exceptions.
Cholesterol except for retnoic acid. Also, amine hormones T3 and T4 behave as steroids therefore are also considered steroid hormones.
Describe steroid synthesis
start with cholesterol (C27) reacts with P450scc to make pregnenalone (C21) whose A ring is oxygenated by 3BHSD to progesterone (C21). From progesterone we can get the androgens, mineralocorticoids, and glucocorticoids by reacting with P450c17 (reaction is varied by regulating the activity of the enzyme via phosphorylation of the P450c17. Can also regulate by varying what enzymes are available in different tissues)
What are the androgens?
dihydotestosterone (C19), testosterone (C19), estrogens (C18).
What is the rate limiting step of steroid synthesis?
Formation of pregnenalone (C21) and getting the cholesterol into the inner mt membrane??
What is an example of mineralocorticoids?
What is an example of glucocorticoid?
Characteristics of steroids (nuclear receptors)?
uses a carrier protein, long half life, receptor is intracellular, mediated by receptor-hormone, is lipid soluble
Characteristics of peptides (catecholamines)?
no carrier protein (unless IGF), water soluble, receptor on the cell membrane, short half life (minutes), mediated by 2nd messengers
Describe the basics of G protein signaling
hormone binds to receptor and causes a conformational change that allows the alpha subunit to bind to GTP instead of GDP. Upon binding GTP, alpha dissociates from beta/gamma and activates another protein that leads to amplification of the signal via 2nd messengers.
Describe cAMP 2nd messenger system
hormone binds to receptor, alpha subunit activated and travels to adenyl cyclase activating it and stimulating it to produce lots of cAMP (amplification). cAMP activates PKA which also phosphorylates many different enzymes (amp). Different hormones can bind to the same receptor and elicit the same response, ex glucagon and epinephrine in the liver (augmentation). PKA stimulates glycogenolysis by inhibiting glycogen synthase, stimulating phosphorylase kinase.
Describe IP3/DAG/Ca2+ 2nd messenger system
hormone binds receptor, conformational change, alpha subunit of G protein activated, activates phospholipase C which cleaves PIP2 into IP3 and DAG. IP3 binds to receptors on the ER causing a release of Ca2+ into the cytosol. IP3 also activates CAM kinase which phosphorylates many enzymes. Ca2+ and DAG activate Protein kinase C which phosphorylates and activates many enzymes. Augmented because different hormones can bind to the same receptor and elicit the same cellular response.
What is gating?
ion channels changing between open and closed conformations
What are the different types of Ca++ channels in the ER/SR?
ion gated, ligand gated via IP3 and ryanodine.
What ions move outward when the membrane potential is 0?
K, the only one with a high concentration inside the cell verses outside!!!
What ions move inward when the membrane potential is 0?
Cl, Na, Ca.
When do ions stop moving?
when the membrane potential is equal and opposite to the ion potential (Eion, aka chemical gradient)
What is the reversal potential?
aka Eion. Determines which way the ions move and predicts the membrane potential based on ion movement
2 mechanisms for Ca++ diffusion into cytosol?
Ca++ channels in the ER/SR and Ca++ permeant channels in the plasma membrane.
2 examples of Ca++ channels in the ER/SR
1. IP3 gated channels on the ER
2. ryanodine channels on the SR in skeletal and cardiac muscle
5 examples of Ca permeant channels (ion channels!) in the plasma membrane
1. voltage-gated Ca channels (CaV)
2. transient receptor potential channels (TRP)
3. Store operated Ca channels (Oria, SOCe)
4. mach receptor (neurotransmitter-gated)
5. glutamate NMDA receptor (neurotransmitter-gated)
How does K regulate cytosolic Ca++ levels?
If K+ channels open- membrane is hyperpolarized and the CaV channels can't open so less Ca in cytosol
If K+ channels closed- membrane potential is depolarized and CaV channels are more open, so more Ca in cytosol
Potassium Aggravated Myotonias (PAM)
defect in the NaV channels resulting in more Na in the skeletal muscle cells than normal, so they are hyper-excitable. Results in myotonia (prolonged contraction) then eventually paralysis. Comes in the form of attacks precipitated by exercising, foods rich in K, or stress. Not a very common disease.
- gain of function
- persistant NaV current because the NaV channels aren't able to inactivate as quickly
- more positive RMP so easier to activate NaV channels