Exam 1 Flashcards
first messengers
outside cell for homeo, hormones and NT.
- categorized by polarity, secretion, composition
polar first messenger
bind to mem, can be desensitized,
- ligand gated, g protein, NO synthase, tyrosine kinase AFTER mem receptor!
agonist
receptor binds with specificity
- does physio response
antagonist
ligand does NOT do response
desensitization
downregulation of receptors due to sustained response
receptor sequestration
whole receptor swallowed by endosome, signal gets pulled back + receptor returns
- done in high affinity binding
receptor down reg
receptor + ligand pulled into a lysosome + destroyed!
- done when 1st molec is ALWAYS present
receptor inactivation
separate signalling pathway gets activated, generates 2nd molec which blocks receptor directly
inactivation of signalling protein
separate signalling pathway gets activated, generates 2nd messenger protein, block’s receptor’s SECOND MESSENGER (indirect block)
production of inhibitory protein
1st molecule activates second which causes receptor A to downreg
- second messenger also does cell response but also -ve feedback
local mediators
short half life, auto and paracrine
- ex inflamation!
- mast cells release histamine
neurotransmitters
1st messenger delivered directly to a synaptic cleft by the terminus
hormones
long 1/2 life to travel in blood and long distance
- endocrine and neurendocrine
- different EMBRYO origins
COMP: AA derived
enzymatic changes in AA generate 1st messenger
- EX. TYROSINE
tyrosine
rate limiting: tyrosine hydroxylase
- hydrophilic manipulations
- tyrosine + o2 = L-dopa -co2+ dopamine + o2 = norepinephrine + methyl = epinephrine
- dopamine, norepi are NT
- epi is hormone
tyrosine and locations
basal ganglia does dopamine (2 enzyme genes)
sympathetic neuron does norpineprhine (3)
adrenal medulla does ephinephrine (4)
COMP: protein
mostly polar
- start of as gene, then trascribe and translated into precursur protein + modified in rough ER and golgi
ex. insulin, pro-opiocortin
Insulin
preproinsulin gets cut by ER and cross linked = proinsulin then golgi cuts off c peptide to give insulin and then secreted into blood (stored in golgi vescicles)
- c peptide is wasted!
- enzymes clip lys-arg and arg-arg
pro-opiocortin
cleaved in corticotrope cells of ANTERIOR PIT
- each is stress/pain related
pro-opiocortin split
1) corticotropin (ACTH) –> a MSH (sunburn!)
2) b lipotropin –> gamma lipotropin, b MSH, b endorphin
corticotropin (ACTH)
- stim release of cortisol from adrenal cortex
MSH
increases pigmentation in melanocytes
lipotropin/endorphin
endogenous opiates
prostegagens
prep uterine lining for preg + maintains
glucocorticoids
cortisol promote gluconeogenesis and degrades fats + proteins
mineralcorticoids
aldosterone act in nephron to increase Na absorption, K and H secretion
androgens/ estrogens
maintain repro development
vitamin D
increase calcium absorption in intestine
cholsteral hormones
prostegagens,glucocorticoids,mineralcorticoids, androgens/ estrogens,vitamin D
- NONPOLAR
cholesterol hormone pathway
LDL transport cholesterol –> released by lysosome to cytoplasmic cholesterol (split 2 ways)
1) kidney, skin, liver, UV modify into vit D
2) enzyme cholesterol desmolase (1st step in steroid hormone process) –> pregnolone –> progesterone
split 2 ways 1) gluco + mineral (enzyme 21- HYDROLASE) 2) androgens –> estrogen
androgen estrogen stuff
1) menopause ovaries stop converting estrogen to androgens so masculinization
2) if mutation with 21- hydrolase, then all progesterone gets turned to androgens (in embryo). male then precocius puberty, and female is hermaphrodism
neurotransmitter receptors when bind acetylcholine
called cholinergic (all membrane bound)
1) nicotinic: ligand - gated. ach binds and changes shape, channel opens
2) muscarinic: second messenger mediated. ach binds, turns second messenger on, which then opens channel
*ach changes the shape of protein and allows channel to open… thus Na+ that flows can be second messenger!
second messengers
intracell receptors that do biochem reactions like increasing speed of signals and increase control in feedback mechs
ex. ligand gates and G proteins
ligand gates
2nd messenger
- receptor itself may be an ion channel that opens upon ligand binding. changes membrane potential and transports calcium
- glutamate, GABA, IP3 receptor?
G s/I proteins
G proteins are GTPases that change shape when ligand binds. G protein exchanges GDP for GTP, alpha subunit releases and diffuses to peripheral enzyme such as adenylyl cyclase and phospholipase C
S is stim, I is inhibitory
** amplifies signal!
G protein adenylyl cyclase
ligand binds, receptor changes shape, alpha subunit gets GTP, converts ATP to cAMP by adenyly cyclase and then returns to receptor
(keeps going until ligand UNbinds)
cAMP then activates protein kinase A which does cell responses
activated by: epi, glucagon, ACTH, TSH, calcitonin
getting rid of cAMP
- regulate this path: ADH, Oxytocin, catecholamines, GF
use cAMP phosphodiesterase even after cAMP production is off, cAMP molecules remain floating around
vibrio cholera
causes cholera (diarrhea) - vibrio toxin binds to receptor and stops alpha subunit ability to hydrolyze GTP to GDP and adenylyl cyclase is always on! increases cAMP which opens ion channels and water leaves
phospholipase C pathway
1st mess binds, receptor changes shape, alpha subunit breaks loose, activates phospholipase C (only with GTP!), which then breaks bown between DAG and PIP2 giving DAG and IP3 (sugar). ip3 then binds to smooth ER receptor releasing calcium. calcium then
1) binds to calmodulin to decrease cAMP (inactication of signalling protein!)
2) binds with DAG to kinase C (adds p to serine or thyroxine)