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The human cell > Lecture 9 and 10 > Flashcards

Lecture 9 and 10 Flashcards

1
Q

What are the two types of regulation that have to occur for all cellular processes?

A

Spatial regulation

Temporal regulation

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2
Q

What does spatial regulation do?

A

Ensures only specific cells respond, or that the process happens in the correct compartment within a cell

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3
Q

What does temporal regulation do?

A

Ensures the process only happens when and for how long they are required

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4
Q

What call all cells do?

A
  • Grow/proliferate
  • Differentiate/specialise
  • Move
  • Apoptosis
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5
Q

What is a kinase?

A

An enzyme that catalyses the phosphorylation of a substrate

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6
Q

What is a phosphate groups formula?

A

PO4^2-

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7
Q

What are the three amino acid groups that protein kinases can phosphorylate in eukaryotes?

A

Serine
Threonine
Tyrosine

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8
Q

What are the three major effects of phosphorylation of a protein?

A
  • Becomes more hydrophillic
  • Conformational change
  • Change in activation status
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9
Q

What are gap junctions?

A

Intercellular connections which allow direct cytoplasmic communication between cells

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10
Q

What characterizes communication in gap junctions?

A

Small molecules pass freely between cells

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11
Q

What is the name of the protein that make up gap junctions?

A

Connexin

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12
Q

What is the name given to each of the two subunits that makes up a gap junction?

A

Connexon (hemichannels)

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13
Q

What do connexons consist of?

A

6 connexin protein molecules

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14
Q

Where are gap junctions common?

A

Where rapid communication is important- muscles (heart), nerve tissue

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15
Q

What is the structure of a connexin protein?

A

4 transmembrane domains, 2 extracellular lops and both intracellular N- and C- terminals

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16
Q

How many different connexins are there in human cells?

A

24

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17
Q

How are connexins named?

A

Based on size

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18
Q

Why are there so many different types of connexins?

A

Composition defines which molecules can pass through gap junction

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19
Q

What are the two groups of gap junction?

A

Homotypic- both hemi channels the same

Heterotypic- two different hemi channels

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20
Q

What do multiple channels comprise?

A

A gap junction plaque

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21
Q

What are endocrine glands?

A

Glands that secrete their products into the blood

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22
Q

What are exocrine glands?

A

Glands that secrete their products out through ducts

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23
Q

What is an autocrine signal?

A

When a ligand acts on the same cell that produced the signal

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24
Q

What is a paracrine signal?

A

When a ligand can act on neighbouring cells

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25
Q

What is a specific type of paracrine signal in which the ligand is on the sending cell and is not released?

A

Juxtacrine

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26
Q

What name is given to the translation of signals?

A

Signal transduction

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27
Q

How do hydrophobic ligands enter the cell?

A

Ligand can cross the plasma membrane and bind to a receptor within the cell

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28
Q

Give an example of a process which involves a hydrophobic ligand

A

Cortisol signalling

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29
Q

What is cortisol an example of?

A

A hormone

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30
Q

What metabolic actions is cortisol signalling involved with?

A

Blood pressure regulation

Suppression of inflammation

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31
Q

How do hydrophillic signals enter the cell?

A

Ligand cannot cross plasma membrane so binds to transmembrane receptor

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32
Q

Is insulin hydrophilic or hydrophobic?

A

Hydrophilic

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33
Q

What name is given to the relaying of hydrophilic signals across the cell membrane?

A

Transmembrane signalling

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34
Q

What is a second messenger?

A

Small ions or molecules that relay signals between locations, generated intracellularly

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35
Q

What is a signalling cascade?

A

A series of reactions initiated by a first messanger acting on a receptor

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36
Q

In what ways can signals be intergrated?

A
  • One receptor activates multiple pathways
  • Multiple receptors activate on pathway
  • Different receptors and different pathways which affect each other
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37
Q

How are signalling proteins activated?

A
  • Binding to other signals
  • Conformational change
  • Membrane targeting
  • Compartmentalisation
  • Covalent modifications
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38
Q

What does signal pathway that is the result of insulin binding to the receptor lead to?

A

Glucose import
Glycogen synthesis
Regulation of gene expression

39
Q

What type of cell in the pancreas produces insulin?

A

Beta cells in the Islets of Langerhans

40
Q

How does insulin reduce blood glucose levels?

A

Stimulates uptake of glucose into muscle and adipose tissue, stimulates glycogen synthesis

41
Q

What receptor does insulin bind to?

A

Tyrosine kinases

42
Q

What is the structure of the tyrosine kinases receptor

A

2 alpha subunits

2 beta subunits

43
Q

What subunits of the receptor does insulin bind to?

A

Alpha subunits

44
Q

What happens when insulin binds to the receptor?

A

A conformational change results in the receptor becoming activated

45
Q

What happens once the tyrosine kinases receptor becomes activated?

A

Insulin receptor substrate 1 (IRS) is phosphorylated (tyrosine is phosphorylated)

46
Q

What is insulin receptor substrate (IRS)?

A

An adaptor protein

47
Q

What happens to IRS once it is activated?

A

It binds to PI3K (a lipid kinase) which is then activated

48
Q

What does activated PI3K do?

A

Catalyzes the addition of a phosphate group to the membrane lipid PIP2, converting it to PIP3

49
Q

What does PIP3 do?

A

Recruits protein kinases to the inner surface of the plasma membrane, phosphorylating protein kinase Akt

50
Q

What does activated Akt do?

A
  • Phosphorylates glycogen synthase kinase-3

- GLUT4 moves from vesicles in the cytosol to the plasma membrane

51
Q

What does phosphorylation of glycogen synthase kinase-3 do?

A

Reduces its activity, increasing the amount of the more active form of glycogen synthase, enhancing glycogen production

52
Q

What happens when GLUT4 transporter is inserted into the membrane?

A

Glucose uptake

53
Q

Why is insulin signalling a key component of glucose homeostasis?

A

Stimulates absorption of glucose and its polymerization into glycogen

54
Q

What is the 2nd messenger in the insulin signaling pathway?

A

PIP3

55
Q

What is the signalling molecule in the insulin signalling pathway?

A

Akt

56
Q

In what 4 ways are signalling proteins activated?

A
  • Binding to other signalling molecules
  • Conformational changes
  • Membrane targeting/compartmentalisation
  • Covalent modifications
57
Q

What are three types of plasma membrane receptors?

A
  • Ligand-gated ion channels
  • Enzyme-linked receptors
  • G protein-coupled receptors (GPCRs)
58
Q

What are ligand-gated channels?

A

Channels triggered by the binding of specific substances to the channel protein

59
Q

What are enzyme linked receptors?

A

Transmembrane receptors where the binding of a extracellular ligand causes enzymatic activity on the intracellular side

60
Q

Guanylyl cyclase receptors result in what enzymatic reaction?

A

Conversion of GTP to cyclic GMP

61
Q

What does cGMP regulate?

A

Vasodilation of blood vessels
Ion channel conductance
Apoptosis
Relaxation of muscles etc.

62
Q

Give an example of a receptor kinase that does not involve a second messenger.

A

Receptor Serine/Threonine kinases, such as transforming growth factor beta signalling

63
Q

What is transforming growth factor beta signalling involved in?

A

Proliferation, differentiation, chemotaxis, immune cells activation

64
Q

What type of molecule is insulin?

A

A dimer

65
Q

What name is given to receptors that bring two monomer ligands together?

A

Dimerise

66
Q

How does dimerisation work?

A

Protein kinase domains on the intercellular domain of the receptors are brought together by interactions on the extracellular domain

67
Q

What name is given when each subunit of dimerised receptors phosphorylate themselves?

A

Autophosphorylate

68
Q

Where is autophosphorylation important?

A

Cell proliferation, survival, migration, etc.

69
Q

What are G proteins?

A

Guanine-nucleotide binding proteins

70
Q

How do G-protein linked receptors activate G proteins?

A

Ligand binding causes a conformational change which activates the G protein

71
Q

Give examples of G protein-linked receptors

A

Olfactory receptors, norepinephrine, hormone, opioid receptors etc.

72
Q

What is the structure of G protein-linked receptors?

A

7 transmembrane alpha helices
N-terminus in extracellular fluid
C-terminus in cytosol
Alternating cytosolic and extracellular loops

73
Q

What gives G protein-linked receptors their specificity?

A

Unique messenger binding site

Cytosolic loops

74
Q

How are G protein-linked receptors regulated?

A

Many ways

Phosphorylation of amino acids in their cytosolic domain

75
Q

What does phosphorylation of amino acids in the cytosolic domain of G protein-linked receptors do?

A

The receptor becomes densensitized

76
Q

What are the two classes of G proteins?

A

Large heterotrimeric G proteins

Small monomeric G proteins

77
Q

What are the 3 subunits of large heterotrimeric G proteins?

A

G alpha, G beta, G gamma

78
Q

What do heterotrimeric G proteins do?

A

Mediate signal transduction through G protein-linked receptors

79
Q

What subunit of G proteins does GTP/GDP bind to?

A

Alpha (the largest of the subunits)

80
Q

In the inactive state, what does the alpha subunit of G-protein bind to?

A

GDP

81
Q

What happens when the ligand binds to the G protein-linked receptor?

A

The receptor binds a G protein, Galpha releases GDP and acquires GTP

82
Q

What happens when Galpha acquires GTP?

A

G alpha and Gbetagamma subunits separate/dissociate

83
Q

What happens to the separated subunits of the activated G protein?

A

The subunits activate/inhibit target molecules

84
Q

Give an example of a signal transduction that involves G proteins.

A

The adenylyl cyclase-cAMP pathway

85
Q

What is cyclic AMP?

A

A second messenger molecule important in many biological processes

86
Q

What is cAMP produces in response to?

A

Glucagon, adrenaline etc.

87
Q

In what ways can signals be terminated?

A
  • Second messengers can be catabolised

- Phosphorylation can be reversed

88
Q

How can signals be terminated when G proteins are involved?

A

Activity of alpha subunit can be terminated by enzymes such as GTPase

89
Q

Give an example of second messengers being catabolised.

A

cAMP/cGMP phosphodiesterase which breaks down cyclic ring

90
Q

What enzymes can reverse phosphorylation?

A

Phosphatases

91
Q

How can signals be amplified?

A
  • By producing more signals

- By preventing signals being turned off

92
Q

How are more signals produced to amplify a signal?

A

Increased 2nd messenger synthesis

93
Q

Give an example of increased 2nd messenger synthesis

A

Forskolin increases cAMP production

94
Q

How can signals be prevented from being turned off?

A

By decreased 2nd messenger degredation, such as when phosphodiesterase mutates

The human cell (10 decks)

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