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Physiology 2410 > Lecture 6- Biochemistry of signaling pathways > Flashcards

Lecture 6- Biochemistry of signaling pathways Flashcards

1
Q

minus gap junction signaling, what does cell to cell signaling require? (3)

A

signal (ligand)
receptor
way to get the message across (intracellular signaling pathways)

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2
Q

what is a signal transduction pathway?

A

information from secreted signals is converted to intracellular signal pathways, therefore, converts one form of signal to another

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3
Q

explain signal transduction (5)

A

signal molecule –> binds to receptor protein –> activates intracellular signal molecules –> causes alterations of target proteins –> creates a biological response

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4
Q

are signal pathways ubiquitous/ everywhere?

A

all cells have some pathways and only certain cells have specific pathways

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5
Q

why are signal pathways important?

A

they amplify signals to cause a large biological effect

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6
Q

what are the two main categories based on receptor location?

A

intracellular receptors
cell membrane receptors

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7
Q

what state are ligands in with intracellular receptors?

A

lipophilic (hydrophobic), therefore fat soluble

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8
Q

with intracellular receptors can ligands diffuse through cell membrane? what do they bind to?

A

yes, then they bind to receptors in the nucleus or cytosol

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9
Q

what do intracellular receptors alter?

A

gene expression (happens slowly but its long lasting)

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10
Q

with intracellular signal receptors is the response fast?

A

no, theyre slower responses that are related to changes in gene activity

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11
Q

what state are ligands in with cell membrane receptors?

A

lipophobic (hydrophilic) water soluble

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12
Q

with cell membrane receptors can ligands diffuse through cell membrane? what do they bind to?

A

no, they bind to membrane receptors which cause intracellular cascade

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13
Q

with cell membrane receptors is the response fast?

A

yes

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14
Q

what are the 4 cell membrane receptors?

A

integrin receptor
receptor channel
receptor- enzyme
G protein- coupled receptor

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15
Q

what does the integrin receptor do?

A

binds extracellular matrix proteins

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16
Q

binding of the ligand with integrin receptor stimulates what change?

A

changes in the cytoskeleton

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17
Q

what can changes in the cytoskeleton affect?

A

cell movement
growth
wound healing

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18
Q

how do receptor channels work?

A

ligand binds to the receptor channel protein and a channel gate either opens or closes (allowing ions to ener and leave).
this alters the cells permeability to an ion and membrane potential

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19
Q

how do receptor channels have an electrical effect?

A

when activated ions cross cell membrane they are charged which causes an electrical signal/ effect

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20
Q

what ligand normally binds to a receptor channel?

A

neurotransmitter

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21
Q

what ion is always allowed into cells through receptor channels?

A

Calcium!!! (important for intracellular signal)
recall: Ca++ inside the cell is low

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22
Q

what are receptor channels often called?

A

ligand- gated ion channels
neurotransmitter gated ion channels
ionotropic receptors

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23
Q

what do receptor enzymes and GPCR have in common?

A

activate amplifier enzymes

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24
Q

how does signal amplification work?

A

receptor- ligand complex activates an amplifier enzyme
1 ligand is amplified into many intracellular molecules

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25
Q

what is the takeaway message about the ligand from signal amplification?

A

a small amount of ligand creates a large effect

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26
Q

what is an example of a receptor enzyme pathway?

A

tyrosine kinase receptor

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27
Q

what is the general goal of tyrosine kinase receptors?

A

to transfer a phosphate group from ATP to a tyrosine residue (amino acid) of a protein which phosphorylates tyrosine residues

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28
Q

what is a specific example of tyrosine kinase receptor?

A

insulin receptor

29
Q

what does a complete insulin receptor contain?

A

alpha receptor (contains ligand binding domain)
beta subunit (is transmembrane and contains the signaling domain

30
Q

how does the insulin receptor work in tyrosine kinase receptor? (7)

A
  1. insulin binds to alpha subunit of receptor
  2. causes activation in beta subunit of the receptor 3. which causes them to dimerize (combine 2 identical units together) and automatically phosphorylate (auto phosphorylate themselves)
  3. beta subunit send the signal of the insulin to the cytoplasm
  4. kinase domain in the cytoplasm is activated
  5. kinase domains on the receptor phosphorylate insulin receptor substrate
  6. other responses in the cell are triggered
31
Q

what are orphan receptors?

A

there are hundreds of known GPCR but many have unknown function

32
Q

what are GPCRs also called?

A

metabotropic receptors
7 transmembrane domain receptor
serpentine receptor

33
Q

why might GPCRs be called 7 transmembrane domain receptor?

A

they have 7 transmembrane proteins

34
Q

what does teh activation of GPCR do?

A

leads to generation/ release of second messengers

35
Q

what are second messengers?

A

signaling molecule synthesized or released by a cell in response to an extracellular signaling molecule like a hormone

36
Q

what are different paths of a second messenger?

A

synthesized
released from a storage compartment

37
Q

what form are second messengers in? hydrophobic, hydrophilic?

A

can be hydrophobic, hydrophilic or a gas

38
Q

what does GPCR stand for?

A

G- protein coupled receptor

39
Q

why are GPCRs called G- proteins?

A

because they bind GDP and GTP (guanosine diphosphate, guanosine triphosphate)

40
Q

what is the inactive configuration of G- proteins?

A

bind GDP

41
Q

what is the active configuration of G- proteins?

A

exchange GDP and GTP

42
Q

what are 3 examples of GPCR?

A

adenylyl cyclase
phospholipase C
arachadonic acid

43
Q

what is the process of Andenylyl cyclase?

A

1.ligand binds to G protein receptor
2. activates the G protein
3. once activated, the G- protein can diffuse along the inside leaf of the membrane
4. G- protein diffuses along the inside of the membrane 5. the amplifier enzyme Adenylyl Cyclase is now activated
6. Adenylyl cyclase converts hundreds of ATP into cAMP
7. cAMP activates protein kinase A (PKA)
8. PKA diffuses within cell to phosphorylate many other proteins

44
Q

what can the activated receptor stimulate in Andenylyl cyclase?

A

several G- proteins

45
Q

what does each G- protein activate in Andenylyl cyclase?

A

each G- protein activates one Andenylyl cyclase

46
Q

what is cAMP in Adenylyl cyclase pathway?

A

second messenger
can diffuse throughout the cell

47
Q

in Andenylyl cyclase does PKA only phosphorylate one type of protein?

A

no, many types of proteins can be phosphorylated, giving rise to complex cellular responses

48
Q

what is the process of phospholipase C in GPCR?

A
  1. ligand binds to and activates G protein receptor
  2. G- protein activates the phospholipase- C (amplifier enzyme)
  3. PLC degrades membrane phospholipids (PIP2)
    into TWO second messengers (diacylglycerol + inositol tri- phosphate), DAG in the membrane stays associated with phospholipid, IP3 is small and polar so it diffuses through the cytoplasm
  4. DAG activates protein kinase C (PKC)
  5. PKC diffuses within the cell and phosphorylates other proteins
  6. IP3 binds to the IP3 receptor on the endoplasmic reticulum
  7. IP3 receptor is activated and allows stores of Ca++ to be released into the cytoplasm
49
Q

what does Ca++ become in phospholipase C?

A

another second messanger

50
Q

what are common second messengers?

A

cAMP
cGMP
IP3
DAG
Ca++

51
Q

what are the 5 different things calcium can do as a second messenger?

A

Ca binds to the calcium- binding protein calmodulin to activate other proteins
Ca binds to motor proteins and allows action of cytoskeleton and motor proteins (muscle contraction)
Ca binds to synaptic proteins to trigger exocytosis
Ca binds to ion channels to modulate their gating (channels can be open all the time or gated (sometimes open, sometimes closed)
Ca in fertilized eggs initiates development

52
Q

how are gases second messengers?

A

only soluble gasses are second messengers however they do bend the definition of second messenger

53
Q

NO is an example of a soluble gas, what is unique about it?

A

has a life of 2- 30 seconds

54
Q

explain the process of the gas nitric oxide (NO) in viagra cialis

A
  1. synthesized by endothelial cell of arteries or neurons of parasympathetic nervous system
  2. diffuse into adjacent arterial smooth muscle
  3. this activates guanylyl cyclase
  4. which produces cGMP
  5. which activates protein kinase G (PKG)
  6. which leads to relaxation of smooth muscle
55
Q

what are two other molecules that do similar things to NO?

A

CO (carbon monoxide)
H2S (hydrogen sulfide)

56
Q

what pathway is the arachidonic acid pathway similar to?

A

phospholipase C (PL-C pathway)

57
Q

how does the arachidonic acid pathway work?

A
  1. G- proteins activate phospholipase A2 (amplifier enzyme)
  2. PLA2 degrades phospholipids into arachidonic acid
58
Q

what are the two major groups of arachidonic acid- derived paracrine molecules to be aware of?

A

leukotrienes
prostaglandins thromboxanes (prostanoids)

59
Q

what are leukotrienes, how did they come about?

A

arachidonic acid –> lipoxygenase –> leukotrienes

singulair tablets are a leukotriene receptor antagonist

60
Q

what are prostaglandins, how did they come about?

A

arachidonic acid –> cycloxygenase –> prostaglandins thromboxanes

aspirin is an anti-inflammatory that binds to cycloxygenase

61
Q

why does the hormone epinephrine (adrenaline) cause some blood vessels to constrict and others to dilate?

A

presence of receptor isoforms

62
Q

what receptor isoform causes the blood vessel to constrict? on what type of blood vessel?

A

alpha receptor
intestinal blood vessel

63
Q

what receptor isoform causes the blood vessel to dilate? on what type of blood vessel?

A

beta receptor
skeletal muscle blood vessel

64
Q

what is the takeaway message about target response?

A

target response depends on the target receptor. thus the same hormone causes different effects of the hormone.
some ligands can activate multiple receptors

65
Q

what does it mean that some receptors are promiscuous?

A

activated by more than one ligand
ex. alpha receptors may be activated by either epinephrine or norepinephrine. beta receptors may be activated by either epinephrine or norepinephrine

66
Q

how many receptors might a cell contain?

A

hundreds or thousands of receptor proteins

67
Q

what does it mean that the numbers of receptors can change over time?

A

need more receptors when developing at a young age

68
Q

receptors can be desensitized, what does that mean?

A

receptors can become over stimulated
ex. people that overuse hard drugs, their tolerance wears off after a while because they over stimulated their receptors causing them to have desensitized receptors

69
Q

what does the phosphorylation of alpha and beta receptors do?

A

causes them to have a lower affinity for ligands

Physiology 2410 (21 decks)

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