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2) Biochemistry II > Biosignaling > Flashcards

Biosignaling Flashcards

1
Q

Do receptors and ligands form covalent or non-covalent bonds?

A

Non-covalent

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2
Q

What are tissue-specific receptors? Give an example.

A
  • Receptors are only present in one or two tissues

- TRH receptor in pituitary cells

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3
Q

What are tissue-specific receptor targets?

A
  • Receptors are present in various tissues, but they respond differently in different cells
  • Adrenalin receptor in the liver increases glycogenolysis and in adipocytes stimulates fatty acid release
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4
Q

What is a receptor?

A

Membrane-bound or soluble protein or protein complex, which exerts a physiological intrinsic effect after binding its natural ligand

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5
Q

What term applies to a situation in which both hormones are bound to receptors on the same cell?

A

Integration

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6
Q

What is signal amplification?

A

When enzymes activate enzymes, the number of affected molecules increases geometrically in an enzyme cascade

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7
Q

What is desensitization/adaptation?

A
  • Receptor decreases its response to a signalling molecule when that agonist is in high concentration
  • Cascadal mediators inhibit the ligand and receptor; stops the response
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8
Q

Give examples of desensitization.

A
  • Smell
  • Bright light to dark light
  • Skin sensation
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9
Q

What is integration?

A

Two different receptors for two different signals modulate for the same response

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10
Q

What does the response of signal integration depend on?

A
  • Depends on many receptor-ligand interactions

- Cells respond to all of them as a whole

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11
Q

Give examples of some signals to which cells respond.

A
  • Antigens
  • Growth factors
  • Hormones
  • Light
  • Neurotransmitters
  • Nutrients
  • Odorants
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12
Q

What are the two ways a ligand-receptor can induce a response?

A
  • Ligand-receptor directly induces a response

- Ligand-receptor –> activity of effectors –> response (indirect)

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13
Q

How many GPCR receptors are there?

A

We don’t know; could be 800 could be more

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14
Q

Which receptor does 50% of drugs target? Give an example.

A
  • GPCR

- Prozac

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15
Q

What is the ligand and the receptor in the cAMP GPCR example?

A
  • Ligand: epinephrine

- B-adrenergic receptor

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16
Q

What is Gs? What does it increase/decrease?

A
  • Stimulates adenylyl cyclase

- Increases levels of cAMP in the cell

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17
Q

What is Gi? What does it increase/decrease?

A
  • Inhibits adenylyl cyclase

- Decreases levels of cAMP in the cell

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18
Q

What is Gq? What does it increase/decrease?

A
  • Activates phospholipase C (PLC)

- Increases calcium levels in the cell

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19
Q

In the cAMP mechanism of a GCPR receptor, what does the Gsa subunit move towards after it dissociates frmo Gsbg?

A

Moves towards adenylyl cyclase

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20
Q

What is the role of adenylyl cyclase in the cAMP mechanism of GCPR?

A

Catalyzes the formation of cAMP from ATP

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21
Q

In the cAMP mechanism of a GCPR receptor, what does cAMP do?

A

Activates PKA

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22
Q

What causes the cellular response to epinephrine in the cAMP mechanism of a GCPR receptor?

A

Phosphorylation of cellular proteins by PKA

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23
Q

How does adenylyl cyclase catalyze the formation of cAMP from ATP?

A

Removes two phosphate groups from ATP

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24
Q

What does AKAP stand for? What is its role? In which mechanism is it located?

A
  • a-kinase anchoring protein
  • Anchors PKA
  • In the cAMP mechanism of a GCPR receptor
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25
Q

What is the structure of the PKA/AKAP complex?

A
  • AKAP anchors 2 PKA subunits (dimer)

- Each PKA subunit has a catalytic subunit and a regulatory subunit

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26
Q

Which subunit does cAMP bind to in the PKA complex?

A

cAMP binds to the regulatory subunit

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27
Q

How many cAMPs are required to activate a dimer of PKA?

A

4 molecules of cAMP for 2 molecules of PKA

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28
Q

How does PKA phosphorylate other proteins?

A

When cAMP binds to the regulatory subunit, the catalytic subunit is released and the substrate-binding cleft is now activated; it can phosphorylate other proteins

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29
Q

Give examples of popular GPCRs.

A
  • Ghrelin receptor
  • Gonado trophin receptor
  • Histamine H1 receptor
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30
Q

If epinephrine binds to a receptor in the liver cell, how many molecules of glucose are generated?

A

If epinephrine = x, glucose = 10 000x

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31
Q

What are the two ways the signal of the cAMP mechanism in a GCPR receptor can be terminated?

A

1) Conversion of cAMP to AMP by cyclic nucleotide phosphodiesterase; since AMP is not functional and cannot activate PKA
2) Modulators of GTPase activity

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32
Q

What converts cAMP to AMP?

A

Cyclic nucleotide

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33
Q

What are the modulators of GTPase activity? (2)

A
  • GAP (GTPase activator protein)

- RGS (Regulators of the G-Protein)

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34
Q

Give two examples of signals that use cAMP as second messengers. Are they Gs or Gi?

A
  • Epinephrine: Gs

- Prostaglandins: Gi

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35
Q

In the IP3 and Ca mechanism in a GPCR, is Gs or Gi used?

A

Neither, Gq is used

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36
Q

What does the activated Gq with GTP move towards in the IP3 and Ca mechanism in a GPCR?

A

Moves towards PLC

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37
Q

What does PLC mean?

A

Phospholipase C

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38
Q

What is the role of PLC? Which mechanism is it implicated in?

A
  • Cleaves PIP2 to IP3 and diacylglycerol

- In the IP3 and Ca mechanism in a GPCR

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39
Q

What is the role of IP3? Which mechanism is it implicated in?

A
  • Binds to a specific receptor-gated Ca2+ channel, releasing sequestered Ca2+
  • In the IP3 and Ca mechanism in a GPCR
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40
Q

What activates protein kinase C? Which mechanism is it implicated in?

A
  • Diacylglycerol and Ca2+

- In the IP3 and Ca mechanism in a GPCR

41
Q

Give examples of signals that act through PLC, IP3 and Ca2+.

A
  • Angiotensin
  • Glutamate
  • Oxytocin
42
Q

What are the three pathways of tyrosine kinase receptors?

A
  • MAPK
  • PIP3
  • JAK-STAT
43
Q

What is the ligand and the receptor in the MAPK pathway example?

A

Ligand: Insulin
Receptor: Insulin receptor

44
Q

Where does the MAPK pathway take place?

A

In the cellular membrane at first, then ERK moves into the nucleus to phosphorylate transcription factors

45
Q

What is PI-3K’s role? Which mechanism is it implicated in?

A
  • Converts PIP2 to PIP3

- PIP3 (RTK)

46
Q

What binds to PIP3? How is it phosphorylated? Which mechanism is it implicated in?

A
  • PKB bound to PIP3
  • PDK1 phosphorylates PKB
  • PIP3 (RTK)
47
Q

What is PKB’s role? Which mechanism is it implicated in?

A
  • Phosphorylates GSK3 on a serine residue

- PIP3 (RTK)

48
Q

What is GSK3’s role when it is active? What does it prevent when its inactive? Which mechanism is it implicated in?

A
  • Convert glycogen synthase (GS) to its inactive form by phosphorylation
  • When GSK3 is inactive, GS remains active and the synthesis of glycogen from glucose is accelerated
49
Q

How is the uptake of glucose increased in the PIP3 mechanism?

A

PKB stimulates movement of glucose transporter GLU4 from internal membrane vesicles to the plasma membrane

50
Q

What does GS mean?

A

Glycogen synthase

51
Q

What does MAPK mean? Why?

A

Mitogen activated protein kinase (simulates mitosis)

52
Q

What does JAK mean?

A

Janus Kinase

53
Q

What does STAT mean?

A

Signal Transducer and Activator of Transcription

54
Q

Why can dimerized STAT travel into the nucleus? Which mechanism is it implicated in?

A
  • Because the dimerization exposes NLS which allows it to travel into the nucleus
  • JAK pathway
55
Q

Which pathway can the JAK mechanism induce?

A

The MAPK cascade to alter gene expression

56
Q

What is ANF? When is it secreted?

A
  • Atrial natriuretic factor

- Hormone secreted by the heart when it is stretched (when the blood volume is high)

57
Q

What signals are implicated when the blood volume is high?

A
  • ANF (stretched heart)
  • Kidney (guanylyl cyclase)
  • Na excretion (draws water out)
  • Reduced blood volume
58
Q

Which ligand and which receptor are used in the guanylyl cyclase example?

A

Ligand: ANF
Receptor: ANF receptor

59
Q

How does the receptor guanylyl cyclase work?

A
  • Guanylyl cyclase converts GTP to cGMP

- Activates PKG

60
Q

Why are there soluble guanylyl cyclases?

A

Soluble since they are in the cytoplasm, not the cell membrane

61
Q

What do soluble guanylyl cyclase proteins all have? What is one of their ligands?

A
  • All have Heme

- Citric oxide (NO)

62
Q

How is the signal terminated in a guanylyl cyclase receptor?

A

cGMP is converted to 5’-GMP by a phosphodiesterase, which terminates the signal

63
Q

What kind of cells are excitable? What processes are controlled by these excitable cells?

A
  • Neurons: neuron signals

- Muscles: muscle contraction

64
Q

Ion channels are “gated”. What can they be stimulated by?

A
  • Ligands (ligand-gated)

- Changes in membrane potential (voltage-gated)

65
Q

What compounds do ion channels allow?

A

Anions or cations

66
Q

Which compounds maintain the membrane in a polarized state?

A
  • Na+
  • K+
  • ATPase
67
Q

What is the resting membrane potential?

A

-70 to -50 mV

68
Q

What is the normal state of the membrane potential?

A

Polarized

69
Q

How are the outside and the inside of the plasma membrane in the normal state of the membrane potential?

A

Outside: +
Inside: -

70
Q

What causes a depolarized membrane potential status?

A
  • Inside is less negative

- Above -50mV

71
Q

What causes a hyperpolarized membrane potential status?

A
  • Inside is more negative

- Below -70mV

72
Q

How does Na+ travel?

A

Outside (high) to inside (low)

High to low

73
Q

How does K+ travel?

A

Inside (high) to outside (low)

High to low

74
Q

How does Ca2+ travel?

A

Outside (high) to inside (low)

High to low

75
Q

How does Cl- travel?

A

Inside (LOW) to outside (HIGH)

LOW TO HIGH

76
Q

Which ion travels from low potential to high potential?

A

Cl-

77
Q

What is a cation? What is an anion?

A

Cation: +
Anion: -

78
Q

What happens when a neuron is excited?

A

Depolarization stimulates ion channels

79
Q

Which ion helps vesicles open and release their neurotransmitter across the synaptic cleft?

A

Ca2+

80
Q

How do Na+ and Ca2+ go into the cell and depolarize the next neuron?

A

Neurotransmitters activate the ligand-gated ion channel

81
Q

In a voltage gated ion channel, what senses a change in potential?

A

Voltage sensor

82
Q

In a voltage gated ion channel, what does the selectivity filter do?

A

Decides what type of ion can go in

83
Q

What allows for the opening of a ligand-gated channel? What influx is allowed in?

A

When ligand binds, it causes a conformational change, which allows for the influx of ions

84
Q

Which receptors allow the influx of cations?

A
  • Acetylcholine
  • Serotonin
  • Glutamate
85
Q

Which receptors allow for the influx of anions?

A

Glycine

86
Q

What is the integrin recognition sequence? What does it mean?

A
  • Arg-Gly-Asp

- Extracellular matrix proteins need Arg-Gly-Asp in order for integrins to recognize

87
Q

In which direction is signal transduction?

A

Bidirectional (inside to outside, or outside to inside)

88
Q

What are integrins?

A

Integrins are proteins that function mechanically, by attaching the cell cytoskeleton to the extracellular matrix, and biochemically, by sensing whether adhesion has occurred.

89
Q

What are integrins connected to on the inside?

A

Actin filaments in the cytoskeleton

90
Q

What are integrins connected to on the outside?

A

Fibronectin in extracellular matrix

91
Q

What two compounds connect integrins to the cytoskeleton? What are their roles?

A
  • Vinculin and talin
  • Can help with cell motility, interact with extracellular matrix (changes shape and movement)
  • Talin and vinculin have been targets as cancer therapy
92
Q

How many different nuclear receptors are encoded in our genome?

A

48-50

93
Q

Nuclear receptors are for what kind of hormones? Why?

A
  • Fat-soluble

- They can diffuse through the cell membrane

94
Q

Where are most nuclear receptors? Where are some?

A
  • Most: cytoplasm

- Some: nucleus

95
Q

Give examples of hormones that can bind to nuclear receptors.

A

Steroid, thyroid, retinoic acid, vitamin D

96
Q

Where does the dimerization of nuclear receptors occur?

A

In the nucleus OR the cytoplasm

97
Q

For each class of steroid nuclear receptors, what % of them can be localized in the plasma membrane?

A

5-10%

98
Q

How do nuclear receptors located in the cytoplasm regulate gene expression?

A

Once dimerization occurs in the cytoplasm, it will MOVE to the nucleus

99
Q

Protein phosphorylation by a kinase occurs on 3 types of amino acids. What are they?

A
  • Serine
  • Threonine
  • Tyrosine

2) Biochemistry II (23 decks)

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