Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Endocrine systems and Reproduction Emily > 002 hydrophilic hormones and enzyme cascade > Flashcards

002 hydrophilic hormones and enzyme cascade Flashcards

1
Q

give some examples of hydrophilic hormones

A
  • proteins e.g. insulin
  • peptides
  • amino acid derivatives e.g. adrenaline
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what is unique about hydrophilic hormones?

A
  • can dissolve into plasma in blood easily as hydrophilic without needing to transport via proteins
    (unless they are already bound to some protein e.g. albumin)
  • however they cant cross plasma membrane as they are hydrophilic so use GPCR
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what do endocrine hormones do?

A
  • act on cells far from the site of release
  • secreted into the blood
  • only target cells that express the receptor
  • e.g. insulin, adrenaline
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what do paracrine hormones do?

A
  • act on nearby cells only
  • diffuse into interstitial fluid and are rapidly inactivated by local enzymes
  • e.g. histamine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what do juxtacrine hormones do?

A
  • the hormone is either bound to the membrane (requiring physical contact between cells)
  • or the hormones is secreted into extracellular matrix
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what do autocrine hormones do?

A
  • act on the cell that released the hormone
  • e.g. T cells, interleukin-2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what are the 4 types of hormone receptors?

A
  • ligand binding ion channels
  • receptor enzymes
  • enzyme-recruiting receptors
  • G-protein coupled receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

describe ligand-gated ion channels and give an example

A
  • the signal is transduced to the cell via a change in membrane potential/ when the ion channel opens
  • e.g. ACh receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

describe receptor enzyme hormone receptors and give an example

A
  • enzymatic activity of receptor is activated by hormone binding
  • e.g. insulin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

describe enzyme recruiting receptors and give an example

A
  • hormone binding induces the recruitment and activation of protein kinases
  • e.g. cytokine receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

describe G-protein coupled receptors and give an example

A
  • hormone binding activates GTP-binding proteins/second messengers
  • e.g. adrenaline receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

describe the pathway of general signal transduction of hormones

A
  1. hormone is released
  2. hormone binds to receptor on plasma membrane of cell, which induces a conformational change in recptor’s cytosolic region that alters its function
  3. concentration of a 2nd messenger increases through enzymatic action
  4. effectors are stimulated or inhibited by second messenger (pumps, enzymes, tfs)
  5. signalling pathway is shut down, effectors return to original state and messengers removed/become ineffective
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

describe the overall process/effects of a hormone binding to a GPCR

A
  • hormone-bound receptor causes the exchange of GDP for GTP, activating G alpha subunit to do different actions
  • G alpha subunit then eventually hydrolysis the GTP back into GDP, becoming inactive again
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what are the 4 types of G alpha (GPCR) subunits?

A
  • Gs, Gi, Gq, Gt
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what is the function of Gs alpha subunits?

A
  • activate adenylyl cyclase –> increase cAMP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what is the function of Gi alpha subunits?

A
  • inhibits adenylyl cyclase –> decreases cAMP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what is the function of Gq alpha subunits?

A
  • activates phospholipase C –> increases DAG, IP3, Ca
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what is the function of Gt alpha subunits?

A
  • activates retinal cyclic GMP phosphodiesterase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what are the different types of GPCR?

A
  • G alpha = s,i,q,t
  • G beta (5 isoforms)
  • G gamma (6 isoforms)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what do G beta and gamma GPCRs do?

A
  • may alter the specificity of receptor G protein binding, cooperate in transduction or shut pathways down
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what enzymes does protein kinase A phosphorylate?

A
  • hormone-sensitive lipase
  • acetyl CoA carboxylase
  • glycogen synthase
  • transcription CREB
    = immediate metabolic effects and long term effects via gene transcription
22
Q

what effects can PKA have in the liver?

A

increase glycogenolysis and gluconeogenesis

23
Q

what effects can PKA have in adipose tissue?

A
  • increase lipolysis
24
Q

what effects can PKA have in ovarian follicles?

A

increases synthesis of oestrogen and progesterone

25
Q

how is the adenylyl cyclase/cAMP/PKA pathway amplified?

A
  • adrenaline receptor complex can catalyse GDP:GTP on multiple G proteins
  • each activated G alpha subunit can only bind to 1 adenylyl cyclase
  • each adenylyl cyclase can catalyse formation of many cAMP
  • 4 cAMP activate 2 PKA
  • each PKA can phosphorylate many things
26
Q

describe the structure and function of receptor enzymes (hormone binding)

A
  • have an extracellular ligand-binding domain and an enzyme active site on the intracellular section, connected by a single transmembrane segment
  • many of the enzymes are tyrosine kinases e.g. the insulin receptor
  • the ligand binding either activates the enzyme activity or brings it in proximity to its target
27
Q

describe the structure and function of receptor tyrosine kinases

A
  • function as dimers with an extracellular hormone-binding domain and an intracellular protein tyrosine kinase domain
  • when hormone binds, RTK monomers cross-phosphorylate each other
  • this makes it an attachment site for proteins with SH2 or PTB domains
    e.g. insulin
28
Q

describe the steps of the MAPK pathway (epidermal growth factor receptor)

A
  1. epidermal growth factor (EGF) binds to each EGFR monomer inducing a structural change = dimerize
  2. proximity of cytosolic domains allows cross-phosphorylation, so PTK is active
  3. tyrosine-phosphates act as docking sites for Grb-2 which is attached to Sos
  4. Sos catalyses exchange of GDP for GTP on membrane bound Ras, activating it
  5. GTP-Ras binds and activates Raf, a membrane-bound protein kinase
  6. a series of protein kinases are phosphorylated and activated e.g. MAPK
  7. P-MAPK phosphorylates transcription factors, altering their activity
29
Q

what is the outcome of the MAPK pathway (EGF)?

A
  • EGF (epidermal growth factor) binds to its receptor causes cross-phosphorylation of its monomers causing cascade of phosphorylation
  • eventually phosphorylates MAPK which then phosphorylates transcription factors
30
Q

what is Sos?

A

a guanine nucleotide exchange factor (GEF)
- catalyses the exchange of GDP for GTP on Ras, but only when it has been recruited to the membrane via Grb-2 (in MAPK/EGF pathway)

31
Q

what is Ras?

A
  • a small G protein
  • monomeric (unlike heterotrimeric G proteins, slower than heterotrimeric)
  • Ras-GTP binds to and activates Raf
32
Q

what is the clinical relevance of Epithelial growth factor receptors and cancer?

A
  • EGFR is overexpressed in some epithelial cancers –> uncontrolled growth
  • a small amount of receptor can dimerize in the absence of ligand (EGFR)
  • this is enough to initiate the cascade and phosphorylate transcription factors, causing the cell to inappropriately grow and divide
  • cetuximab (therapeutic antibody) targets and blocks the extracellular domain of the receptor preventing it from dimerises = halting cancer
  • used in colorectal cancer
33
Q

describe the PI-3K/insulin receptor signalling pathway

A
  1. insulin binds to dimeric receptor, causing PTK to cross-phosphorylase
  2. first round of cross-P fully activated kinase activity and then cross-Ps again
  3. these phosphorylated tyrosine residues act as docking sites for IRS-1, which is then phosphorylated
  4. P-IRS-1 can now bind PI-3K at membrane which now phosphorylates PIP2 into PIP3
  5. PIP3 allows PDK1 and PKB to associate with the membrane
  6. PKB is phosphorylated and dissociates from membrane and phosphorylates target proteins
34
Q

what is the use/outcome of the PI-3K/insulin receptor pathway?

A
  • responsible for GLUT4 translocation to allow glucose transport for blood glucose regulation
35
Q

what is the function of IRS-1(insulin receptor substrate-1)?

A
  • insulin receptor substrate-1is phosphorylated on several tyrosine residues
  • IRS-1 is already associated with the membrane due to its PH domain which can bind to PIP2
  • IRS-1 is a docking protein, it can bind to may proteins, including Grb-2 (activating MAPK pathway)
  • therefore insulin can simultaneously stimulate numerous pathways with different effects
36
Q

what is the function of transforming growth factor (TGF-beta)?

A
  • TGF- beta family is a large family of proteins involved in regulating development
  • in most cells they prevent proliferation by inducing synthesis of proteins that inhibit the cell cycle
  • also plays a role in tissue organisation, promoting expression of extracellular matrix proteins and adhesion molecules
37
Q

describe the transforming growth factor (TGF-B) receptor signalling pathway

A
  1. TGF-B binds to TBR-II
  2. then bind to TBR-I and phosphorylates its glycine serine rich domain (GS), activating serine/threonine kinase
  3. TBR-I can then phosphorylate a class of transcription factors called R-Smads
  4. upon phosphorylation 2 R-Smads and a Co-Smad form a heterotrimer, and nuclear localization signals are also exposed
  5. in nucleus, heterotrimer interacts with transcription factors
38
Q

what is the clinical relevance of the TGF-B receptor and cancer?

A
  • the TGF-B receptor pathway often inhibits growth in cells
  • loss of either TBRI or TBRI function due to inactivating mutations is found in many human tumours
  • these tumours are resistant to growth inhibition by TGF-B
  • mutations in the Smad proteins also prevent TGF-B signalling, most pancreatic cancers contains a deletion in a Co-Smad
39
Q

describe the structure and function of cytokine hormone receptors

A
  • cytokines are a family of small signalling molecules with a characteristic arrangement of 4 alpha helices, controlling the growth and differentiation of a number of cells
  • cytokine receptors recruit an enzyme (no intrinsic enzyme activity)
  • the receptors all have a tyrosine kinase called JAK bound to their cytosolic domains which phosphorylate transcription members of the Signal Transduction and Activation of Transcription (STAT) family
  • cytokine receptors can activate other pathways (e.g. MAPK)
  • however JAK/STAT pathway is only activated by cytokines
40
Q

what is erythropoietin?

A
  • a cytokine released by the kidney in response to low blood O2
41
Q

what is the function of erythropoietin receptor signaling pathway?

A
  • stimulate the transcription of genes in erythroid progenitors that prevent them from undergoing apoptosis and stimulate them to differentiate into erythrocytes
    (to increase blood O2 capacity)
42
Q

what is the clinical/sport relevance of erythropoietin?

A
  • the use of supplemental erythropoietin to increase the level of erythrocytes in blood in banned in international athletic competitions
  • it is dangerous as surplus erythrocytes can clot small blood vessels causing stroke
43
Q

describe the steps of the erythropoietin receptor signalling pathway

A
  1. dimeric JAK2 kinase with low activity is bound to cytosolic domain of EpoR
  2. Epo simultaneously binds 2 EpoRs, bringing JAK kinases close enough for to phosphorylate each other
  3. this lowers Km of kinase for its substrate, activating it
  4. JAK kinases phosphorylate receptors allow STAT5 to bind and also be phosphorylated
  5. phosphorylated STAT5s dissociate from receptor, dimerize, exposing nuclear localisation sequence
  6. STAT5 dimer enters nucleus and its DNA-binding domain binds to specific DNA regulatory sequences to control expression of target genes
44
Q

describe the switching off JAK/STAT pathway

A
  • SHP1 is a phosphotyrosine phosphatase, that binds phosphorylated receptor and dephosphorylates JAK kinase, inhibiting pathway when cytokines are no longer binding to receptor
  • mutation in erythropoietin receptor can lead to unable to bind to SHP1 phosphatase –> resulting in increased intracellular signalling, so more RBCs than normal
45
Q

what kind of receptor are the adrenaline signaling pathway?

A
  • GPCR
  • specifically Gsa
46
Q

what kind of receptor are the tyrosine kinases?

A
  • intracellular enzyme receptors
47
Q

what kind of receptor pathway is the epidermal growth factor receptor in?

A
  • intracellular enzyme receptors
  • tyrosine kinases
48
Q

what kind of receptor pathway is the insulin receptor in?

A
  • intracellular enzyme receptor
  • tyrosine kinases
49
Q

what kind of receptor pathway is the transforming growth factor B receptors in?

A
  • intracellular enzyme receptor
50
Q

what kind of receptor pathway is the erythropoietin receptor in?

A
  • enzyme recruiting receptors
  • cytokine receptors

Endocrine systems and Reproduction Emily (2 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions