Lecture 9 and 10 Flashcards
(94 cards)
1
Q
What are the two types of regulation that have to occur for all cellular processes?
A
Spatial regulation
Temporal regulation
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
3
Q
What does temporal regulation do?
A
Ensures the process only happens when and for how long they are required
4
Q
What call all cells do?
A
- Grow/proliferate
- Differentiate/specialise
- Move
- Apoptosis
5
Q
What is a kinase?
A
An enzyme that catalyses the phosphorylation of a substrate
6
Q
What is a phosphate groups formula?
A
PO4^2-
7
Q
What are the three amino acid groups that protein kinases can phosphorylate in eukaryotes?
A
Serine
Threonine
Tyrosine
8
Q
What are the three major effects of phosphorylation of a protein?
A
- Becomes more hydrophillic
- Conformational change
- Change in activation status
9
Q
What are gap junctions?
A
Intercellular connections which allow direct cytoplasmic communication between cells
10
Q
What characterizes communication in gap junctions?
A
Small molecules pass freely between cells
11
Q
What is the name of the protein that make up gap junctions?
A
Connexin
12
Q
What is the name given to each of the two subunits that makes up a gap junction?
A
Connexon (hemichannels)
13
Q
What do connexons consist of?
A
6 connexin protein molecules
14
Q
Where are gap junctions common?
A
Where rapid communication is important- muscles (heart), nerve tissue
15
Q
What is the structure of a connexin protein?
A
4 transmembrane domains, 2 extracellular lops and both intracellular N- and C- terminals
16
Q
How many different connexins are there in human cells?
A
24
17
Q
How are connexins named?
A
Based on size
18
Q
Why are there so many different types of connexins?
A
Composition defines which molecules can pass through gap junction
19
Q
What are the two groups of gap junction?
A
Homotypic- both hemi channels the same
Heterotypic- two different hemi channels
20
Q
What do multiple channels comprise?
A
A gap junction plaque
21
Q
What are endocrine glands?
A
Glands that secrete their products into the blood
22
Q
What are exocrine glands?
A
Glands that secrete their products out through ducts
23
Q
What is an autocrine signal?
A
When a ligand acts on the same cell that produced the signal
24
Q
What is a paracrine signal?
A
When a ligand can act on neighbouring cells
25
What is a specific type of paracrine signal in which the ligand is on the sending cell and is not released?
Juxtacrine
26
What name is given to the translation of signals?
Signal transduction
27
How do hydrophobic ligands enter the cell?
Ligand can cross the plasma membrane and bind to a receptor within the cell
28
Give an example of a process which involves a hydrophobic ligand
Cortisol signalling
29
What is cortisol an example of?
A hormone
30
What metabolic actions is cortisol signalling involved with?
Blood pressure regulation
| Suppression of inflammation
31
How do hydrophillic signals enter the cell?
Ligand cannot cross plasma membrane so binds to transmembrane receptor
32
Is insulin hydrophilic or hydrophobic?
Hydrophilic
33
What name is given to the relaying of hydrophilic signals across the cell membrane?
Transmembrane signalling
34
What is a second messenger?
Small ions or molecules that relay signals between locations, generated intracellularly
35
What is a signalling cascade?
A series of reactions initiated by a first messanger acting on a receptor
36
In what ways can signals be intergrated?
- One receptor activates multiple pathways
- Multiple receptors activate on pathway
- Different receptors and different pathways which affect each other
37
How are signalling proteins activated?
- Binding to other signals
- Conformational change
- Membrane targeting
- Compartmentalisation
- Covalent modifications
38
What does signal pathway that is the result of insulin binding to the receptor lead to?
Glucose import
Glycogen synthesis
Regulation of gene expression
39
What type of cell in the pancreas produces insulin?
Beta cells in the Islets of Langerhans
40
How does insulin reduce blood glucose levels?
Stimulates uptake of glucose into muscle and adipose tissue, stimulates glycogen synthesis
41
What receptor does insulin bind to?
Tyrosine kinases
42
What is the structure of the tyrosine kinases receptor
2 alpha subunits
| 2 beta subunits
43
What subunits of the receptor does insulin bind to?
Alpha subunits
44
What happens when insulin binds to the receptor?
A conformational change results in the receptor becoming activated
45
What happens once the tyrosine kinases receptor becomes activated?
Insulin receptor substrate 1 (IRS) is phosphorylated (tyrosine is phosphorylated)
46
What is insulin receptor substrate (IRS)?
An adaptor protein
47
What happens to IRS once it is activated?
It binds to PI3K (a lipid kinase) which is then activated
48
What does activated PI3K do?
Catalyzes the addition of a phosphate group to the membrane lipid PIP2, converting it to PIP3
49
What does PIP3 do?
Recruits protein kinases to the inner surface of the plasma membrane, phosphorylating protein kinase Akt
50
What does activated Akt do?
- Phosphorylates glycogen synthase kinase-3
| - GLUT4 moves from vesicles in the cytosol to the plasma membrane
51
What does phosphorylation of glycogen synthase kinase-3 do?
Reduces its activity, increasing the amount of the more active form of glycogen synthase, enhancing glycogen production
52
What happens when GLUT4 transporter is inserted into the membrane?
Glucose uptake
53
Why is insulin signalling a key component of glucose homeostasis?
Stimulates absorption of glucose and its polymerization into glycogen
54
What is the 2nd messenger in the insulin signaling pathway?
PIP3
55
What is the signalling molecule in the insulin signalling pathway?
Akt
56
In what 4 ways are signalling proteins activated?
- Binding to other signalling molecules
- Conformational changes
- Membrane targeting/compartmentalisation
- Covalent modifications
57
What are three types of plasma membrane receptors?
- Ligand-gated ion channels
- Enzyme-linked receptors
- G protein-coupled receptors (GPCRs)
58
What are ligand-gated channels?
Channels triggered by the binding of specific substances to the channel protein
59
What are enzyme linked receptors?
Transmembrane receptors where the binding of a extracellular ligand causes enzymatic activity on the intracellular side
60
Guanylyl cyclase receptors result in what enzymatic reaction?
Conversion of GTP to cyclic GMP
61
What does cGMP regulate?
Vasodilation of blood vessels
Ion channel conductance
Apoptosis
Relaxation of muscles etc.
62
Give an example of a receptor kinase that does not involve a second messenger.
Receptor Serine/Threonine kinases, such as transforming growth factor beta signalling
63
What is transforming growth factor beta signalling involved in?
Proliferation, differentiation, chemotaxis, immune cells activation
64
What type of molecule is insulin?
A dimer
65
What name is given to receptors that bring two monomer ligands together?
Dimerise
66
How does dimerisation work?
Protein kinase domains on the intercellular domain of the receptors are brought together by interactions on the extracellular domain
67
What name is given when each subunit of dimerised receptors phosphorylate themselves?
Autophosphorylate
68
Where is autophosphorylation important?
Cell proliferation, survival, migration, etc.
69
What are G proteins?
Guanine-nucleotide binding proteins
70
How do G-protein linked receptors activate G proteins?
Ligand binding causes a conformational change which activates the G protein
71
Give examples of G protein-linked receptors
Olfactory receptors, norepinephrine, hormone, opioid receptors etc.
72
What is the structure of G protein-linked receptors?
7 transmembrane alpha helices
N-terminus in extracellular fluid
C-terminus in cytosol
Alternating cytosolic and extracellular loops
73
What gives G protein-linked receptors their specificity?
Unique messenger binding site
| Cytosolic loops
74
How are G protein-linked receptors regulated?
Many ways
| Phosphorylation of amino acids in their cytosolic domain
75
What does phosphorylation of amino acids in the cytosolic domain of G protein-linked receptors do?
The receptor becomes densensitized
76
What are the two classes of G proteins?
Large heterotrimeric G proteins
| Small monomeric G proteins
77
What are the 3 subunits of large heterotrimeric G proteins?
G alpha, G beta, G gamma
78
What do heterotrimeric G proteins do?
Mediate signal transduction through G protein-linked receptors
79
What subunit of G proteins does GTP/GDP bind to?
Alpha (the largest of the subunits)
80
In the inactive state, what does the alpha subunit of G-protein bind to?
GDP
81
What happens when the ligand binds to the G protein-linked receptor?
The receptor binds a G protein, Galpha releases GDP and acquires GTP
82
What happens when Galpha acquires GTP?
G alpha and Gbetagamma subunits separate/dissociate
83
What happens to the separated subunits of the activated G protein?
The subunits activate/inhibit target molecules
84
Give an example of a signal transduction that involves G proteins.
The adenylyl cyclase-cAMP pathway
85
What is cyclic AMP?
A second messenger molecule important in many biological processes
86
What is cAMP produces in response to?
Glucagon, adrenaline etc.
87
In what ways can signals be terminated?
- Second messengers can be catabolised
| - Phosphorylation can be reversed
88
How can signals be terminated when G proteins are involved?
Activity of alpha subunit can be terminated by enzymes such as GTPase
89
Give an example of second messengers being catabolised.
cAMP/cGMP phosphodiesterase which breaks down cyclic ring
90
What enzymes can reverse phosphorylation?
Phosphatases
91
How can signals be amplified?
- By producing more signals
| - By preventing signals being turned off
92
How are more signals produced to amplify a signal?
Increased 2nd messenger synthesis
93
Give an example of increased 2nd messenger synthesis
Forskolin increases cAMP production
94
How can signals be prevented from being turned off?
By decreased 2nd messenger degredation, such as when phosphodiesterase mutates
