6. Endocrine - Hormones Flashcards
Hormone vs autacoid and NT
Hormones - chem messenger ductless gland release circ travel distant targ cell act spec protei rec
Autacoid
chem messenger - act target cell close site release
local hormone/ paracrine
Histamine / PG
NT chem messenger - rel neurones act adjacent cell usually neurones periph - adjace effect muscle or gland action rapid - broef durn NA/ACH
MOA hormones
Present in blood stream low conc -targ cell need spec/sensitive - recog and resspon
Spec -receptor
all recept are protein nature
Combo - hormone and receptor - signal = specfic response
Classif hormones
Receptor locn
signal mediates action
Group 1
Lipophilic - receptor intracellu
Steroid - gluc minereal sex
Calctriol - not steroid derived prescuorse
thyroid
retonic acid
Group 2
hydrophilic horm - Rec in membrane
IIa- cAmp as second mssgr
ADH, Beta adreg, tsh
IIB
CGmp
ANP
IIc
Calciu,/pdei - 2nd
Musc recp oxytocin gastrin
IID- second messgr not est
GH Insulin prolactin
Could you outline major diff grp 1 & Grp 2
Grp1 steroid & thyorid - all lipphilic - carried bound tport prot
long t1/2
rec = intrace;; second mssgr - act hormone rec complex - bind spec part DNA - alter prodctuion mRNA
Grp 2
Hydrophillic - not bound protein blood and short t1.2
Typically not pro bound blood
short half lices
receptor - loc cell membrane - activation w/ receptor - sep second messenger
Second messenger?
Third mssgr
Chem mssgr -
Formed result spec hormone recptor combination
Acts intrcell - affect metab processes
Second msgr - intermid carry signal horm to site action
Kinase casdes - act cell second messgr - metabolic alterations in cell
Insulin
51aa hormone
B cell islet langehans panc
major anabolic hormone
carb lip pro metab
Two peptide chain disuplh bridge
Rem cpept precursor proinsulin
Actions Insulin carbohydrate metabolism
Lower pl gluc - gluc enter cells
Insulin combine spec membrane bound recprot - diff effect diff cells - two types response act rec
Increased act spec gluc tport membrane
act TK on B subunit rec
Cells effect
Mesucle adipose - incrase facil diff gluc into cyto = carrier prote
hepato
Increase entry gluc - conseq change intracell metabolism
cell
activity membrane carrier - not increased insulin - norm permeable
Intracell metabo
increase glucokinase - trap clu in cell
increased glycogenis - inc act gluc sythn - inhib glycogen phosporylase
increase oxidation glucose -
inhib gluc 6 phos -> glycolyis / conversion to starch/glyocgen
All main fav diffusion gradeint gluc hepatocyt e- keep gluc conc low
No diffrect effect inulin gluc entry most other cell
indir chjange occur in blood glucose level - msucel and adipose 80% body - effect inslin improtant over all metabolism
Does insulin act AVw/ CAMP
No
Insul - cell membran rece - autophos TK intrcell part B sub
affect activtyy intracell enxyme - meidate activated intracell pro kinase - protein cascde - probable third messenger
Effect insulin on lipid protein metabolism
Lipid
Increase entry glucose into adipose cell - increase syn fatty acids in cells - insulin receptor
increased activity lipoprot lipas e- blood increased bdown tg in chlyomicron to fa - enter adipose
Act hormonse sensitive lipase adipose inhib
intracell bdown fat adipose inhibited
Protein metab
Increased activity - glyolyic path - hepatocytes - decrease gluconeo from AA
metob protein aa into energy decreased - protein sparing effect insulin
Increase entry AA muscle and adipose
Net result - increased store fat and ptoein
anabolic action insulin
Does insulin cross bbb or placenta
No -
No direct effect on neuronal glucose uptake
powerful indir effect change in plasma gluc
brain norm gluc almost excluse as substrae - adeq gluc reequired fucntion
brains RQ .99 - total use carb
Maternal insulin increase during preg - almost double by 3rd trimester
Overcome insulin resitsance d/t place hormone esp hum placetn lactogen. oetriol, progest
Ensure adeq mat pro synth
Regulation of blood glucose
4-7 ref range
fal 3-3.5 fasting
neo lower
2.2 min
Outline factors involved in control blood gluc
Glucostat fxn liver?
Blood gluc - main narrow - despite vary intrake
Body mech - prevent hyperhlyc - fater meal
Input glucose into blood
Gut- small bowel
episdoic vary
Liver - gluc fall - releases gluc into blood
hormonal reg
Output muslce and adipose - take up uptake dep need Urine gluc high - lost in urine
Gucodtat liver - buffer increase and decrease
How factor min flux in blood gluc after meal fasting
carb meal
Blod gluc rise - absorebed
senosre b cell det increase and relase insulin
Liver - insulin entry - by enz effect
muscle and adipose - two thrid taken up liver
major store - glycogen - some oxidose to Co2 - some util in FA synth
Muslce and adpose - increase entry - convereted stor carbn glycogen muscle cell gyler fat cell
glyerol util synth TG
Blood gluc return normal
Fasting
Gluc level fall -
Insulin
sens panc det dcerease - insulin falls
Result reer effect hep enzy - glycogenlysis, gluconeogen increase G6Phos
more gluc release liver
Glucagon
Acell - sense decrease+ gluc sec increase
Gluc bind - rec hepatocyte - rises cAMP
Spec enz activated – glycogenolysis + gluconeo
requires cortisol
Resul synergistic falling inmsulin rising gluca - increase rel gluc liver into blood
Why is sugar control so important
Main reason gypoglc - only energy sub in CN -retina
Uptake depend adeq blood gluc level - not affect insulin
Hypergly:
osmotic effect - dehydrate
lost urine - wawste
osmotic diures loss fluid and electo
Glucose stores
Glyocgen live rand muscle
branched polymer - con a1,4 a1,6 link
Glycogen broken down - rel cell blood main pl guc
Glyco - muscle broken gluc reside - meatb muscle - gluc not relase muscel
No g6 phosp in muslce
Sto glucose - glycogen osmotic effect smaller than glucose molecule
Max total size glyco store 100 liver 400g muslce
500 gr - 2000kclas energy 24h supply
Gluc store circ small
blood gluc 1g/L
5g gluc whole circ
Total gluc ecf - 10g
Equv 40kclas
proveides site - cells recieve supply
Other insulin glucagon - what hormones effect gluc level
Corticosteroid
Permsisve glucagon exert effect liver - increase gluconeo
Hypo - increase secretion
inhib utilatsion gluc - favour fat util body cell
Increase blood blucose level -
diabetes occurs excess cortico
Catechol - adren
Increase blood gluc - hpeatic glycogen output liver
lrise
GH sec increase hypogly inhib gluc uptake musl cell inc rel gluc liver rise
Thyrpod
Increase GIt abs gluc
may decr - hep glycogen-increase blood gluc level
Oestro - insulin restiance mil
Progest - insulin resitance
HPL - insulin resitsance
increase
Soatostatin
inhib relase insulin glucagon indir effect bgl
Plasma glucose levels in baby after birth
Pl gluc fall min 2.8 by 6h birth
Main foetal supply mother
transpalcetan
birth source suddenyl lost
low or no carb intake
Hep glyco - maj source inital period birth
falling insulin increased glucagon
symp stim contrib increased glycogen - main gluc
Glyocgen depleted newborn - mob tg - ffa rise - alternative energy source
incrased level catechol - import causing change fat metab - catechol effective rasing FFA than raising glucose
Introduction provide gluc - stabil plasma days aftrer birth
Net atp prod
Glcolysis cytopalsm 1gluc -> 2 pyruvate - 2 atp +2nadh pyruvate oxidse to acetyl CoA 2NADH/pyruvate then enter krebs - citric acid cycle
Krebs
Mitochonddia - 2atp 8nadh 2fadh2
ETP mitochon 32 atp
Synth thyroid hormones
Where in the bowel is dietary iodide absorbed
Diet iodine con to idodie abosrbed upper SB
typical west diet contrain more than min amt idoide reqd
Idodide in BS taken thryroid or excreted in urine
Synthesis throyid hormones
T4 T3 syhtn gland
1 Uptake Iodewdi in folluc cell active tpor tport against elec grad and conc grad carrier subj competitive inhib other anion 0 similar size to idodie anion r/f iodide uptake inhib
Iodide iodine diffuse folluc lumen - reacts tyr to prod MIT
cat thy perox
Thyrosine AA reside - held peptide link - thyroglobulin - reaction cell coloid interface
Further Iodination MIT - prod DIT
TWO DIT oxida couple throytix - remin aa backobne thryoglob
MIT and DIT - reside T2 reside
How are hormone secreted
Stored colloid part thyroglob - secrretion
glob undergo endocyto into cyto of follic cell
Join lyossymes and thryoglob digested release free thryorix t2 mit dit
t3 + t4 secreted but t4 higher
both high protein bound carrier prote and blumin
mIT AND DIT brokken down and iodied recycle
How is secretion cotrlled
Hypothol prod TRH
reach ant pit - hpyohseal prot circ - release TSH fyhrotrope ant pit
TSH bind GPCR in membrane follicular cell
AC Activate - result increase Iodide uptake increased synthesis - relase thyroid hormones
Free T3 + T4 provide neg feedback - inhib release TRH hypothal - inhib TSH rel ant pit
Pituitary
Post - ADH and Oxytocin
Struc sim nonapept
Struct ant pit
pars tubertalise intermidus distalis
Ant develop thakes pouch
Ant most pars dstalis - all trophic
Proteins
GH
Prolaction
Glycoprote -
FSH
LH
TSH
Polypept
ACTH
MSH
Which cells prod hormones
acidophil - HG Prlaction
Basopl glycoprote and polypept
Control calcium
Ref range
what {ca icf]
[Ca in bag blood]
2.2-2.55
free Ca ++ 50%
Ca bound alb 45%
Ca complexes 5-10%
Low 100nm grad free ca - 10000
ecf 1mM ICF 100nM
0 calcium bound citrate - mech ensure not clot
Type coagulip caused hypocal
None ca- low enough affect coag not compat life
Hypocalc massive tfusion depress contractily
Mech maintain ca blood level stable
ECF [Ca] fairly tight hormnaol control - predom PTH, calcitonin, 1 25 dihtdo - caltriol
calcitrol act vit d
Plasma [ca] control sign
PTH
release pth gland response hypoCa
act bone kidney - indirect gut calcitriol - rise plasma Ca
Calcitriol Formed kidney act bone and gut intest abosrp ca increased osteclast act increased Actions rise plasma ca
Calcitonin
parafollic thyroid cell
effective lower Ca - phys role not est
Renal actions PTH
Reabs Ca dist tube
Decrease reab Phos prox tube
Increase Calcitriol - prox tub cell
Net reslts - plus act PTH on bone - increa ca mobil and act calcitriol bowel = net increased plasma [Ca]
How do hormones interact w/ cells
Hormones attach spec recportop on or in cells
Most recport in cell memnbrae some locate nucleus or cytoplasm
Brin biolog change - occupatin ligand alter effector mech
1 Intermed couplin gmech to effector
receptor connect effector mech thru intermed coupling mech gpor - result second messenger ion channel
2 Ligan gated Ion channel
Ligan bind direct ion chanell and affect open / closing
gaba receprot cl chanell
nic rec Na
3 Bind intracell rec affter tcipt mRNA
bind intracell rec affect cpsepc mrna bind DNA
Receptor both ligand bind and enzymatic fxn
Rec - enzym activty which act conform change ligand bind
tk act gf Gcycl anp
What are gpro
Cell embrane assoc pro - import signal tduction
Hetertrimer 3 sub unit a b y
diff gene subunit cominbed - diff gpor
a - def effect usual interact effector mech
bind gdp and gtp
nuceoltide - guanosine analoge adp and atp resepct
inactive state GDP bound grpo
gdp dissoc + gtp bind = grpo act
Diff gpro
Gs - stim effect ac act
Gi inhib AC inhib
Gt involve photorecp eye
Gq inbolbe Plc reg
How gpro involved signal transduction mech
Coupling between activation spec receptor cell membrane and activation effector mech - affect intracell process
Activation of effector - AC Plc - production second messenger
Ion channel - affect directly or by second messnger (Ca IP3)
signal carried accross membrane by process
Signall mech provides amplication signal
Amplification signal:
Intric gtpase activity of activated gpo important sev reasons
1 Rate hyrdol gtp slow
- assists sustain signal allow greater amplication
2 Slef reg gpro - terminate own activty certain time
3 Directionalaity - reaction propagates 1 direct
What are fts of receptors couple gpro
Signif struct sim gpcr - superfamily
all consits single polypept chain - 7 transmembrane a helical segment
specific ligand binds in pocket between transmembrane signal
How does GPro signal transduction signal work
Seq event
Modules work sequence - cary excell signal - across cell embrane and activate specific second messenger in cell
Ligand bind spec gpcr - membrane
confomrational change - result spec assoc gpro activate
a subunit gpro - release gdp and binds gtp
gpro sep gtpa + gtpby
gtpa - interact effector protein (enz/íchan)
results activation or inhib of enzyme - or open / close channel
GTP hydro to GDP - gtpase act a subunit
and gdp aby inactive form and gpro - reconsitiude
Ex - nind norad to beta act SA Act GS AC act Camp prod Gs act hydro gtp ->gdp
Name sone non gpro horomones / nt
ACH- nic rec
GABA at gaba
Steroid + thyroid - bind intracell rec
Insulin + insulin rec
ANP + guanylate cyclate act
Metabolic rate
Rate energy production body
all energy apperas heat - form w/ highest entropy
Thermal equil - all heat must be lost
WHAT is the BMR
Metabolic rate - standard cond
rest
room temp
12h after meal
result repot as % above or below age adjust standard value
How is it determind
Calorimetry
direct
- Total amt heat energy prod body ody
subject -atwater benedict chamber
met rate - amt heat energyt in 1 hr
Indirrect
est - measure o2 consump as its proportional
o2 consumo 250ml min - 15l hr
mult 4.8 72.3 kcal hr
divide by body surf area - standrd result
typical 70kg - 40kcals m2
How is o2 consumption measured
Subjects breath oxy from wet spiurometer
exp co2 absorbed
circ close and co2 abs
rate decrease equal to oxy cosnump
cona be connected rotating ddrum - circu vvol v time
slope proportioal o2 consump
why is oxygen consumption to bmr
Vast maj energy derived aerobic metab
prod atp via ox phos mito obligatory a/w fixed o2 consump
final rx etpc
cyto ox
- irrev
2H 1/2 O2 => H20
