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BMS242 Cell and Molecular > L20 - Intracellular Receptors > Flashcards

L20 - Intracellular Receptors Flashcards

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1
Q

Describe the strcuture of the signal if it is to act intracellualrly

A

Must be hydrophobic enough and must be small enogh

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2
Q

What are the two main types of receptor

A

Cell surface receptor

Intracellular receptor

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3
Q

What are the two types of an intracellular receptor

A

Gases and nucelar receptor

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4
Q

What two substances to intracellular gas receptors bind

A

NO and CO

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5
Q

What types of molecules do nuclear receptors bind

A

Steroid hormones
Thyroid hormones
Retinoids
Vit D

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6
Q

What are the properites of nitric oxide

A

Gaseous
Free radical
Very reactive

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7
Q

What is the hlaf life of nitric oxide

A

5-10s

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8
Q

The fact NO is a free radical means what

A

That it has an unpaired electron in its outer shell

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9
Q

What is NO2

A

Nitrogen dioxide

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10
Q

What is N2O

A

Nitrous oxide

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11
Q

What is NO

A

Nitric oxide

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12
Q

What is NO synthesisded from

A

L-arginen

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13
Q

L-argine undergoes a ___________ to form _______

A

An oxidation

Forms N-hydroxyarginine

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14
Q

N-hydroxyargine undergoes a _________ to form ______________ and ______

A

Oxidation

L-citrulline and NO

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15
Q

So it can be said NO is synthesised by ___

A

Two successive oxidations

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16
Q

What molecule is produces as waste from NO syntheseis (how many)

A

2 molecules of water - produced at each oxidaition reaction

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17
Q

What enzyme catlayses the synthesis of NO

A

NOS

Nitric oxide synthease

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18
Q

The two oxidations in NO synthesis are analgous to the

A

NADPH dependent cytochrome P450 oxidorectuctase

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19
Q

What is cNOS

A

Consitutive NOS

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20
Q

cNOS

Enzymatic activity
Expression
Activity
How much NO

A

Enyzmatic act. induced by Ca/Calmodulin
Expression is constitutive
Activity is short lived
Picomoles of NO are produced

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21
Q

What are the two types of cNOS

A

eNOS and nNOS

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22
Q

What is eNOS

A

Endothelial

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23
Q

where is eNOS found within the cell

A

Bound at the cell membrane

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24
Q

Which cells express eNOS

A

Endothelium, cardiac myocytesm renal mesangial cells, oesteoblasts/fibroblasts and platelets

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25
What is nNOS
Neural
26
Where is nNOS found within the cell
Cytosol
27
what cells express nNOS
CNS NANC neurones ENS Retina
28
What is iNOS
Inducible
29
iNOS Enzymatic activity Expression Activity How much NO
Enxymatic activity is constitutive Expression is inducible Long lasting Nanomoles of NO are produced
30
What induces the transcription of iNOS
Pathological stimuli - LPS, IFN-g and IL-1
31
What cells express iNOS
Macrophages and Kupfferr cells Neutrophils Fibroblasts Vascular smooth muscle and endothelila cells
32
What is the main effect of NO in the vasculature
Vasodilaiton
33
Describe how NO causes vasodilation in the vasculature
ANS release Ach whuch acts on endothelial cells containing eNOS Endothelila cells release NO which causes the surrounding smooth muscle to relax
34
What are the other effects of NO in the vasculature These properties make NO a
Inhibition of platelet aggregation and vascular smooth muscle proliferations Termed an anti-atherisclerotic
35
Describe the process of NO induction
``` Ach from the NAS Activation of eNOS Acts on argine --> NO Rapid diffusion of NO away NO activates guanylyl cyclase GTP --> cGMP Causes a rapid relaxation of the smooth muscle ```
36
Describe how increased cGMP leads to the relaxtion of the smooth muscle
cGMP Activates cGMP dependent protein kinase (PKG) Myosin light chain phosphatase Acts on the myosine light chain
37
Describe the location of nNOS in the brain
Tethered to NMDA type glutamate receptors
38
What can nNOS in the brain respond to
Ca increase near the open channels
39
What effect does Ca have on nNOS
Activates - causes the production of NO
40
NO produced by nNOS in the brain does what
Diffuses back to the presynaptic terminal where it activayes glutamate production
41
At the presynaptic terminal what is the effect of NO
Increase the production of glutamate | Thus creating a state of long term potentiation
42
What is the effect of NO in the immune system
Kills bacteral and parasites | Induces programmed cell death
43
How is the NO produced in inflammatory cells used as
Cytostatic and cytotoxic agent - involving muchhigher amounts of NO
44
What dieseas can be caused by overproduction of NO iin the lungs and intestines
Rheumatoid arthritus Crohns Asthma
45
Describe the composition of synamite
Nitroglycerine and fine clay as the stabiliser
46
What is nitroglycerine used as a treatment for How does this work?
100 year treatment for angina It is rapidly broken down into NO which causes the relaxation of the blood vessels reducing the load on the heart
47
What is the main symptom and cause for angina
Pain resulting from inadequet blood flow to the heart
48
What enzyme does NO act on
Guanylyl cyclase
49
NO causes the build up of what molecule
cGMP
50
Build up of cGMP is counteracted by
Phospho-diesterase 5
51
What does PDE-5 prevent
Build of of cGMP
52
How does viagra act
Inhibits phosphodiesterase-5
53
What is the mechanism for viagra actions
Inhib of PDE-5 Less breakdown of cGMP so more cGMP produced Smooth muscles constricting the blood vessles relax So more blood flow
54
Steroid hormones made from
Cholesterol
55
Thyroid hormones made from
Tyrosine
56
Retinoids like RA are made from
Vitamin A
57
What do retinoids act as
Local mediators in vertebrate developement
58
What is the solubility of retinoids, and steriod hormone
Poorly soluble
59
How do poorly soluble molecules - steroid and theyroid hormones become soluble so that they can travel in the blood
Bind to specific carrier proteins from which they can disociate from before entering a target cell
60
How are nuclear receptors kept in the inactive state
By inhibitory proteins
61
Describe what happens when a ligand binds to a nuclear receptor
Binding of the ligand removes the inhibitor leading to a conformational change The receptors now interact with coactivtor to direct trnascriptipn
62
What dos the DNA bidning domain of each nuclear receptor contain
Two repeats of C4 zince fingers
63
What is a C4 zinc finger
Where the zinc is bound by four conserved cyteinines
64
What are the domains of the oestrogen receptor
``` N terminal domain DNA binding Hinge region Ligand binding C-terminal domain ```
65
What does the DNA binding domain of the oestrogen receptor consist of
Zinc fingers - each of which binds to specific DNA sequences
66
Describe the binidng of nuclear receptors as homorodimers
Bind as symmetric homodierms to an inverted repeat (so head to head)
67
Examples of intraceullualr receptors which bind as homodimers
Glucocorticoid receptesos and oestrogen receptors
68
Describe the binding of intracellular receptors as heterodimers
Bind as heterodimers with RXR to direct repeat sides (head-tail)
69
What nuclear receptors bind as heterodimers
VitaminD, thyroid hormone and RA receptors
70
What is RXR (what does it stand for)
Retinoid X receptor
71
Head to head binding of nuclear recptors seen in
Symmetrical homodimers binding to an inverted repeat
72
Receptors that bind with RXR bind as ___________ to __________________
Heterodimers | Direct repeat
73
In the absence of ligand where are homodimeric receptors found
In the cytoplasm
74
What causes the translocation of the receptor to the nucelus
Hormone binding to the receptor
75
How are homodimeric receptors kept in the cytoplasm when there is no lignd bound
Anchored in the cytoplasm buy inhibitor proetins including Hsp90
76
What is Hsp90 a relative of
Hsp70
77
What does hormone bidning cause for homodimeric receptors
Release of the inhibitor proteins allowing them to enter the nucleus
78
Where are heterodimeric receptors always found
In the nucleus - with or without the ligand present
79
How do heterodimeric receptors act in the absense of a ligand
Recruitment of histone deacetylases
80
How do heterodimeric receptors act in presence of a ligand
Acts as an activator by the recruitment of histone acetylases
81
Describe the early primary response to steroid hormone
Steriod hormone - receptor complex activates primary response genes Induces synthesis of a few proteins
82
What is the time frame of the early prmary response
1-6 hours
83
Describe the secondary response
A primary response protein shuts off the primary response genes A primary response protein turns on secondary response genes Induces synthesis secondary response proteins
84
What is the time frame for delayed secondary response
6-48 hours

BMS242 Cell and Molecular (26 decks)

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