Flashcards in Exam 1 Deck (97)
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!
receptor binds with specificity
- does physio response
ligand does NOT do response
downregulation of receptors due to sustained response
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
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
short half life, auto and paracrine
- ex inflamation!
- mast cells release histamine
1st messenger delivered directly to a synaptic cleft by the terminus
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
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)
- start of as gene, then trascribe and translated into precursur protein + modified in rough ER and golgi
ex. insulin, pro-opiocortin
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
cleaved in corticotrope cells of ANTERIOR PIT
- each is stress/pain related
1) corticotropin (ACTH) --> a MSH (sunburn!)
2) b lipotropin --> gamma lipotropin, b MSH, b endorphin
- stim release of cortisol from adrenal cortex
increases pigmentation in melanocytes
prep uterine lining for preg + maintains
cortisol promote gluconeogenesis and degrades fats + proteins
aldosterone act in nephron to increase Na absorption, K and H secretion
maintain repro development
increase calcium absorption in intestine
prostegagens,glucocorticoids,mineralcorticoids, androgens/ estrogens,vitamin D
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!
intracell receptors that do biochem reactions like increasing speed of signals and increase control in feedback mechs
ex. ligand gates and G proteins
- 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
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)
special phospholipid on INTRACELL
1st messenger binds to receptor on endothelium of blood and activates NO synthase
- this turns l-arganine and NADPH to Nitrix oxide (nonpolar)
- NO diffuses through to smooth muscle and activates NO guanylate cyclase protein to make cGMP = smooth muscle relaxation
smooth muscle relaxation
vasodilation means more blood flow
can be direct or indirect
- both ways, kinase cause phosphate binding to a tyrosine AA
direct tyrosine kinase
ex. insulin ligand
- kinase has tyrosine AA IN it, and the ligand adds a p directly, which changes shape
- directly adds a phosphate to another enzyme?
indirect tyrosine kinase
a and b are separate portions of the receptor, and the ligand binds them together to make the whole receptor, this then pulls in kinases that phosphorylate such as JAK and STAT
- ex growth factor, cytokine
kinase A, and tyrosine kinase both...
kinase C does NOT (serine or thyronine)
embryo starts as cells, hollows out then forms a tube. this is ENDODERM. tube then has finger-like projections called diverticula which form stuff
oral ectoderm has diverticulum called rathke's pouch, which grows UP. when infundibulum meets the pouch, pouch breaks down. part of puch continues to form anterior lobe of pituitary!
- originates in endoderm so ADENO
inside hypothal there is infundibulum, which grows down and forms median eminence (controls pit gland, neural tissue). this then grows posterior lobe
- neuro origin!
how is the anterior lobe connected to median eminence control?
using the hypothalamic pituitary portal system.
- median eminence has neurosecretory cells (neuroendocrine) which secrete hormone into cap bed 1, which then travel to cap bed 2 and bind to cells in anterior pit (endocrine) and then they release hormone
pituitary gland anatomy
located in small bony cavity formed by sphenoid bone of skull (wings of bone cradle the cranium and has fossa extending). grove of sphenoid is called sella turcica
- confined space means that any tumor can increase pressure and cause gland to be crushed!
- also shearing forces in concussion can rip out pituitary stalk!
NUCLEI IN HYPOTHAL: paraventricular nucleus secretes oxytocin and supraoptic nuc secretes ADH/Vasopressin release
STORED IN PP TO RELEASE in BLOOD
ADH and osmolarity
iso-osmotic is 270-300 mOsm (normonatremia)
- maintains this pressure
low solute and high water outside cell, water moves inside the cell
high solute and low water outside cell, cell then shrinks!
pressure in semi-permeable membrane that stops water moving from high to low
in hyposmotic, ADH
cell swells, ADH level drops, less water is reabsorbed (less water in blood), more volume of dilute urine
in hyperosmotic, ADH
cell shrinks, increase ADH levels, high water reabsorption (high water in blood), low vol of concentrated urine
hypothal releases "releasing hormone" in cap bed 1, then anterior pit releases "-trope" to release another hormone
Hypothal: GHRH anterior pit cells: somatotropes release: GH affects: liver
Hypothal: corticotrope releasing hormone anterior pit cells: corticotrope release: ACTH affects: adrenal cortex to release gluco, mineralocorticoids and androgens
Hypothal: thyrotropin RH anterior pit cells: thyrotropes release: TSH affects: thyroid
Hypothal: gonadotropin RH anterior pit cells: somatotropes release: FSH/ LH affects: ovary and testes to make estrogen/proges or testos
Hypothal: prolactin INHIBITORY or RH anterior pit cells: lactotropes release: prolactin affects: breast
*can inhibit too
released from hypothal and stops GH, TSH, and prolactin
two ways to stop GH
1) somatostatin from median eminence or 2) somatomedin from liver!
Increase protein synth by metabolising gluc and fats for energy, also cause liver to release somatomedin (causes long bone growth!)
made of collagen (protein with three strands enforced with hydroxyapatite so high tensile strength).
bone making process
chondrocytes lay down collagen models, osteoblasts replace with bone. these get trapped in bone so called osteocytes.
- can be a single trebeculae or osteon (concentric rings)
blood vessel lies in middle of layer called haversian canal. osteocytes get nutrients from canals since they sit in hollow cavity with fluid called lacunae. connected by cannaliculi
long bone growth
Gh and metabolism
- increases AA uptake, stops catabolism, increase transcription translation etc by making energy available! want to be hyperglycemic. stop storage of glucose so PREVENT skeletal muscle uptake and adipose tissue taking it. skeletal muscle doesnt' LET GO OF GLUC!
- increases gluconeogenesis by making ketone bodies (2 acetyl's). body uses ketone body not gluc (for brain)
45 % of anterior pit cells are somatotropes!
gives us energy for breakfast (hyperglycemia)
gives MORE gh then hyperglycemia, pancreas will release insulin and burn out the beta cells. this is diabetes melitus (type 1)
- if its after puberty, growth hormone will cause regular bone growth (not long bone!) so feet/face etc grow
adenoma in pituitary (
filled with follicles with colloid fluid thyroglobulin
- cells have apical membrane (inside) and basal lateral membrane (outside)
- parafollicular c cells surround the follicles
T3 and T4 release
hypothal: thyrotropic releasing hormone
anterior pit: thyrotrope cells release TSH
thyroid gland then makes 7% t3 and 93% t4
** t3 and t4 can also block both anterior pit and hypothal!
t3 vs t4
t 3 is active, t4 takes time to lose iodine. we have three months supply. more released in cold weather to increase metabolism. there is a delay of t4 release so april t3 is actually t4 from march.
TSH in blood does what
in blood it goes thru thyroid gland by binding to receptor on basal lateral membrane then 1) make thyroglobulin and move iodone or 2) make/break t3 and t4
DNA/RNA/Protein then sticking out of protein is AA tyrosine
make t3 and t4
TSH increases activity of iodine receptors, which use atp to bring iodine from basal lateral mem. go thru apical membrane and is now charged. to uncharge this, a peroxidase oxidizes. then iodine is added to thyroglobulin tyrosine.
2 iodines + tyrosine = diiodotyrosine
1 iodine + tyrosine = monoiodotyrosine
these will then get conjugated in colloid.
2 DIT = t4 --> thyroxine
DIT + MIT = T3
then into blood by endocytosis
breakdown of t3 and t4?
done to maintain homeostasis.
what t3 does
turns on genes generate atp using gluconeogenesis and glycogeneolysis
- increase protein catabolism, increase FA in blood
- use that ATP in cell with sodium potassium pump
- causes increase in mito number, increase SA of christae, increase in ETC
- increase number of na/k pumps to move ATP
** only 10% of atp is used to move! rest is heat thus INCREASE in body temp!
3 na out 2k in
non-metabolic effects of T3/t4
proper dev of CNA, bone growth
accumulation of glycoproteins, decrease HR, lethargy, goiter
goiter and more t3/t4 stuff increase
when increase calcium, release calcitonin and put ca back in bone. kidney deals with calcium in tissue. stops osteoclasts
parathyroid glands in thyroid release PTH. starts rapid phase: bind to osteocyte and blast receptors. bone cells will stop picking up ca which accumulates in blood. if this doesn't work in min/ hours then start slow phase. osteoclasts release citric and lactic acid to dissolve bone.
hormone released when low calcium. cause calcium to be absorbed in intestine
membrane potentials and calcium
hypercalcemia: increases the membrane potential (harder to generate AP)
hypocalcemia: decreases membrane potential (easier to generate AP). if too low, then muscles always contracted and can cause suffocation!!
caused naturally by GH and cortisol!!
adrenal cortex formation
endocrine tissue pinching off and neutral tissue growing in.
all stress lads
Medulla is neural and the cortex is endocrine
adrenal cortex layers
hypothal: corticotropic releasing hormone anterior pit: corticotrope cells release ACTH stim adrenal cortex to release cortisol
* ACTH primes glomerulosa and reticula to be able to release cortisol when signal comes
* Cortisol is also a primer for GH!
Gh can't work without
cortisol immunosuppression theories
1) immune requires lots of energy and cortisol diverts it away to muscles
2) immune cells leave bloodstream and go back to "Stations" cells not down but just protecting sites. die pretty quick tho
ex. finals getting sick after
low cortisol and low aldosterone. this means no feedback on ACTH and so increase ACTH. pro-opiocortin = high MSH! hyperpigmentation