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BMS242 Cell and Molecular > L20 - Intracellular Receptors > Flashcards

L20 - Intracellular Receptors Flashcards

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
Q

What is nNOS

A

Neural

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26
Q

Where is nNOS found within the cell

A

Cytosol

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27
Q

what cells express nNOS

A

CNS
NANC neurones
ENS
Retina

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28
Q

What is iNOS

A

Inducible

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29
Q

iNOS

Enzymatic activity
Expression
Activity
How much NO

A

Enxymatic activity is constitutive
Expression is inducible
Long lasting
Nanomoles of NO are produced

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30
Q

What induces the transcription of iNOS

A

Pathological stimuli - LPS, IFN-g and IL-1

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31
Q

What cells express iNOS

A

Macrophages and Kupfferr cells
Neutrophils
Fibroblasts
Vascular smooth muscle and endothelila cells

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32
Q

What is the main effect of NO in the vasculature

A

Vasodilaiton

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33
Q

Describe how NO causes vasodilation in the vasculature

A

ANS release Ach whuch acts on endothelial cells containing eNOS
Endothelila cells release NO which causes the surrounding smooth muscle to relax

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34
Q

What are the other effects of NO in the vasculature

These properties make NO a

A

Inhibition of platelet aggregation and vascular smooth muscle proliferations

Termed an anti-atherisclerotic

35
Q

Describe the process of NO induction

A 
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
Q

Describe how increased cGMP leads to the relaxtion of the smooth muscle

A

cGMP
Activates cGMP dependent protein kinase (PKG)
Myosin light chain phosphatase
Acts on the myosine light chain

37
Q

Describe the location of nNOS in the brain

A

Tethered to NMDA type glutamate receptors

38
Q

What can nNOS in the brain respond to

A

Ca increase near the open channels

39
Q

What effect does Ca have on nNOS

A

Activates - causes the production of NO

40
Q

NO produced by nNOS in the brain does what

A

Diffuses back to the presynaptic terminal where it activayes glutamate production

41
Q

At the presynaptic terminal what is the effect of NO

A

Increase the production of glutamate

Thus creating a state of long term potentiation

42
Q

What is the effect of NO in the immune system

A

Kills bacteral and parasites

Induces programmed cell death

43
Q

How is the NO produced in inflammatory cells used as

A

Cytostatic and cytotoxic agent - involving muchhigher amounts of NO

44
Q

What dieseas can be caused by overproduction of NO iin the lungs and intestines

A

Rheumatoid arthritus
Crohns
Asthma

45
Q

Describe the composition of synamite

A

Nitroglycerine and fine clay as the stabiliser

46
Q

What is nitroglycerine used as a treatment for

How does this work?

A

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
Q

What is the main symptom and cause for angina

A

Pain resulting from inadequet blood flow to the heart

48
Q

What enzyme does NO act on

A

Guanylyl cyclase

49
Q

NO causes the build up of what molecule

A

cGMP

50
Q

Build up of cGMP is counteracted by

A

Phospho-diesterase 5

51
Q

What does PDE-5 prevent

A

Build of of cGMP

52
Q

How does viagra act

A

Inhibits phosphodiesterase-5

53
Q

What is the mechanism for viagra actions

A

Inhib of PDE-5
Less breakdown of cGMP so more cGMP produced
Smooth muscles constricting the blood vessles relax
So more blood flow

54
Q

Steroid hormones made from

A

Cholesterol

55
Q

Thyroid hormones made from

A

Tyrosine

56
Q

Retinoids like RA are made from

A

Vitamin A

57
Q

What do retinoids act as

A

Local mediators in vertebrate developement

58
Q

What is the solubility of retinoids, and steriod hormone

A

Poorly soluble

59
Q

How do poorly soluble molecules - steroid and theyroid hormones become soluble so that they can travel in the blood

A

Bind to specific carrier proteins from which they can disociate from before entering a target cell

60
Q

How are nuclear receptors kept in the inactive state

A

By inhibitory proteins

61
Q

Describe what happens when a ligand binds to a nuclear receptor

A

Binding of the ligand removes the inhibitor leading to a conformational change
The receptors now interact with coactivtor to direct trnascriptipn

62
Q

What dos the DNA bidning domain of each nuclear receptor contain

A

Two repeats of C4 zince fingers

63
Q

What is a C4 zinc finger

A

Where the zinc is bound by four conserved cyteinines

64
Q

What are the domains of the oestrogen receptor

A 
N terminal domain 
DNA binding 
Hinge region 
Ligand binding 
C-terminal domain
65
Q

What does the DNA binding domain of the oestrogen receptor consist of

A

Zinc fingers - each of which binds to specific DNA sequences

66
Q

Describe the binidng of nuclear receptors as homorodimers

A

Bind as symmetric homodierms to an inverted repeat (so head to head)

67
Q

Examples of intraceullualr receptors which bind as homodimers

A

Glucocorticoid receptesos and oestrogen receptors

68
Q

Describe the binding of intracellular receptors as heterodimers

A

Bind as heterodimers with RXR to direct repeat sides (head-tail)

69
Q

What nuclear receptors bind as heterodimers

A

VitaminD, thyroid hormone and RA receptors

70
Q

What is RXR (what does it stand for)

A

Retinoid X receptor

71
Q

Head to head binding of nuclear recptors seen in

A

Symmetrical homodimers binding to an inverted repeat

72
Q

Receptors that bind with RXR bind as ___________ to __________________

A

Heterodimers

Direct repeat

73
Q

In the absence of ligand where are homodimeric receptors found

A

In the cytoplasm

74
Q

What causes the translocation of the receptor to the nucelus

A

Hormone binding to the receptor

75
Q

How are homodimeric receptors kept in the cytoplasm when there is no lignd bound

A

Anchored in the cytoplasm buy inhibitor proetins including Hsp90

76
Q

What is Hsp90 a relative of

A

Hsp70

77
Q

What does hormone bidning cause for homodimeric receptors

A

Release of the inhibitor proteins allowing them to enter the nucleus

78
Q

Where are heterodimeric receptors always found

A

In the nucleus - with or without the ligand present

79
Q

How do heterodimeric receptors act in the absense of a ligand

A

Recruitment of histone deacetylases

80
Q

How do heterodimeric receptors act in presence of a ligand

A

Acts as an activator by the recruitment of histone acetylases

81
Q

Describe the early primary response to steroid hormone

A

Steriod hormone - receptor complex activates primary response genes
Induces synthesis of a few proteins

82
Q

What is the time frame of the early prmary response

A

1-6 hours

83
Q

Describe the secondary response

A

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
Q

What is the time frame for delayed secondary response

A

6-48 hours

BMS242 Cell and Molecular (26 decks)

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