Lecture 19 - Biochemical Signaling Flashcards

1
Q

_____ is the body’s fastest source of energy

A

glucose

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2
Q

what must be regulated in order to maintain homeostasis?

A

blood glucose

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3
Q

when is glucose stored as insulin?

A

fed state

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4
Q

when is glucose stored as glucagon?

A

fasting state

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5
Q

when is glucose stored as epinephrine?

A

stress state

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6
Q

what does insulin do? (fuel)

A

turns on fuel storage and biomolecular synthesis

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7
Q

what do epinephrine ad glucagon do? (fuel)

A

-turn on fuel consumption and mobilize glucose from glycogen

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8
Q

what is the general mechanism of signal transduction pathways?

A

receptor
transducer
effector

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9
Q

what is an antagonist?

A

-an alternative stimulus that binds to the receptor and shuts down its response

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10
Q

what is an agonist?

A

an alternate stimulus that binds to the receptor causing similar response to the intended binder

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11
Q

what is a more detailed general mech of signal transduction? (7)

A
  1. external stimulus
  2. membrane receptor
  3. transducer
  4. effector enzyme
  5. second messenger
    (DNA binding)
  6. cytoplasmic and nuclear effectors
  7. cellular response
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12
Q

what is the basic epinephrine receptor scheme?

A
  • epinephrine passes its signal via TM protein

- triggers a second messenger

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13
Q

what does the insulin receptor use?

A

direct relay

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14
Q

what is the receptor scheme for a steroid?

A

-bind directly to nuclear receptors

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15
Q

what are the 6 key steps to epinephrine signaling?

A
  1. epinephrine binds to GPCR on cell surface
  2. transmembrane GPCR passes signal to G protein on inner membrane
  3. G protein activates adenylate cyclase in a cascade (AC)
  4. AC catalyzes formation of the “second messenger” cAMP from ATP
  5. cAMP acts in cytosol to activate PKA
  6. PKA catalyzes the phosphorylation of protein enzymes needed in a gylcogen breakdown
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16
Q

what does epinephrine bind to on the cell surface?

A
  • adrenergic receptors

- adrenergic receptors are examples of G-protein coupled GPCRs

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17
Q

what do GPCRs do?

A

pass the signal to G proteins on innner membrane

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18
Q

what are G proteins?

A

signal transducers

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19
Q

Gprotein is a ______

A

heterotrimer

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20
Q

what is a heterotrimer?

A

consists of

  1. a fatty-acid linked alpha subunit
  2. beta subunit
  3. prenaylated gamma subunit
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21
Q

what does hetertrimer carry in its inactive form/

A

GDP

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22
Q

where do G proteins diffuse on the membrane?

A

inner leaflet to find an activation signal from GPCR

23
Q

what happens once GPCR is activated?

A

-binds GTP and alpha unit dissociates

24
Q

what happens to the activated alpha unit?

A

-diffuses laterally across the membrane to activate adenylate cyclase (AC)

25
what happens after AC is activated?
GTP hydrolyzes slowly back to GDP
26
how long do active G proteins have?
3 min expiration clock
27
what do bacterial toxins (cholera) do?
- block GTP hydrolysis | - puts the cell into perpetual AC activity
28
What do G proteins activate/inactivate?
adenylate cyclase (AC) in a cascade
29
What is AC consist of?
two transmembrane domains (M1 and M2) and two cytosolic domains (C1 and C2)
30
What happen to C1 and C2 when AC is activated by Gs?
they dimerize
31
What does activated AC catalyze?
the formation of cAMP from ATP in the cytosol
32
where is cAMP released from?
the membrane bound AC into the cytosol
33
what does cAMP act as?
second messenger | -itself becoming the stimulus in the interior of the cell
34
what does cAMP activate?
protein kinase A PKA in the cytosol
35
What is PKA?
R2C2 tetramer that binds cAMP cooperatively to release the catalytically active C subunits to produce phosphorylation on Ser and Thr
36
what is the phosphoinositide pathway?
-generate 2 second messengers
37
What is PIP2?
minor membrane component located on the inner leaflet
38
what happens after the signal transduction to a G-protein Gq?
enzyme phospholipase C (PLC) hydrolyzes PIP2 to diaclyglycerol (DAG) and IP3
39
what does IP3 do?
- diffuses through the cytosol | - opens Ca2+ channels in ER from the lumen
40
What is clocking facilitated by?
-rapid degredation of IP3 in the cytosl
41
how can PKC exist?
both in a systolic and a membrane associated from
42
where is PKC activated?
-on the inner membrane by DAG and Ca2+
43
what does the insuline receptor consist of?
3. autophosphorylation, each subunit of RTK dimer catalyzes the phosphorylation of the other subunit
44
what does insulin bind to?
two RTKs
45
what happens when insulin binds to two RTKs?
dimerize
46
what is the first portion of insulin signaling called?
-autophosphorylation
47
what is autophosphorylation?
each subunit of the RTK dimer catalyzes the phosphorylation of the other subunit
48
what does the phosphorylated RTK dimer catalyze?
phosphorylation of certain cystolic proteins to set off a cascade
49
what is RTK signaling also mediated by?
PIP2
50
what happens to PIP2?
phosphorylated to PI3
51
what does PIP3 do?
- serves as second messenger | - activate a series of target proteins in the cell through kinases
52
what are 4 steps of hormone signaling?
1. steroid hormones diffuse through membrane 2. receptors on cytoplasmic side bind them 3. receptor complex delivers hormone to nucleus, modulates transcription of nearby genes 4. signaling mediated by nuclear receptors
53
how do nuclear receptors work?
act over much longer timescale because their stimuli usually act as growth factors or for cell differentiation
54
what are HREs?
- receptor complex delivers hormone to nucleus | - binding to DNA on hormone response elements (HREs)