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Molecules and Cells > Molecular Basis of Health and Disease > Flashcards

Molecular Basis of Health and Disease Flashcards

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1
Q

what are the different systems within the body

A

nervous
respiratory
circulatory
digestive

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2
Q

what does the nervous system do

A

allow us to receive and respond to our environment

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3
Q

what does the respiratory system do

A

breathe and take up oxygen and expel carbon dioxide

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4
Q

what does the circulatory system do

A

deliver oxygen and nutrients throughout the body

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5
Q

what does the digestive system do

A

extract energy and nutrients from food

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6
Q

what are cells

A

functional units of life

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7
Q

describe the structure of cells

A

each cell is a discrete package of material surrounded by plasma membrane

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8
Q

what does the plasma membrane function as on the cells

A

provides a clear boundary between the outside of the cell and the inside of the cell and allows the cells to regulate and control the substances from entering and leaving cells

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9
Q

is the cytoplasm thick

A

no it is watery

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10
Q

what are the organelles within the cytoplasm described as functioning for

A

they are all the machinery and equipment necessary to perform all the physiological processes required to sustain life

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11
Q

what are some single celled organisms

A

protozoa and bacteria

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12
Q

why do cells communicate

A

so they can respond to their environment

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13
Q

how is cell communication achieved

A

through a network of signalling pathways essential for coordinated physiological responses

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14
Q

are all the signals sent and received by cells in their existences essential for healthy development of tissues and organ systems

A

yes

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15
Q

what can disruption in cell communication pathways lead to

A

disruption of normal physiological processes leading to pathology

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16
Q

what do the origins of disease emerge at the level of

A

cell communication pathways

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17
Q

what are the three key concepts in molecular basis of health and disease

A
  • cell communication pathways regulate all aspects of biological function across all physiological levels
  • disrupted cell communication pathways often manifest as disease
  • drugs target disrupt cell communication pathways for therapeutic benefit
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18
Q

what are the levels to basis of health and disease

A

molecular
microscopic
macroscopic
environmental

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19
Q

what is included in the molecular level of basis of health and disease

A

cell signalling, gene expression, protein expression

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20
Q

what can changes in gene expression modify

A

cell behaviour

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21
Q

what does the central dogma explain

A

essentially the process of dna becoming proteins through transcription and translation

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22
Q

what acts as the structural and functional machinery of our cell

A

proteins

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23
Q

what does the range of proteins in the cell determine

A

cell structure and function; what it is and what it can do, as well as which signal the cell can respond to in the future.

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24
Q

what is effective cell communication essential for

A

maintaining the normal structure and function, and regulate all biological activity and maintain homeostasis at the level of our tissues organs and organ systems

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25
Q

what do cell communication pathways govern

A

our movements, thoughts and behaviours

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26
Q

what is involved at the microscopic level

A

cell structure and function

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27
Q

what is involved at the macroscopic level

A

tissues, organs, organ systems and their function

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28
Q

what is involved at the environmental level

A

chronic infection, dysbiosis, diet, physical inactivity, obesity, isolation, chronic stress, disturbed sleep and xenobiotics

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29
Q

what is the purpose of the environmental level of the basis of health and disease

A

look at how the environment can interact with our genes to modify our risk of disease

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30
Q

what are some factors that can disrupt our homeostatis mechanisms and alter the signals our cells receive. our cells respond to those signals by modifying their pattern of gene expression

A
  • chronic infection
  • dysbiosis
  • diet
  • physical inactivity
  • obesity
  • isolation
  • chronic stress
  • disturbed sleep
  • xenobiotics
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31
Q

what is an example of an environment factor and how it can affect the basis of health and disease

A

a diet high in carbohydrates will disrupt our glucose metabolic pathways in our cells and predispose us to type two diabetes

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32
Q

what is ateology

A

the cause of pathogenesis

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33
Q

what does the molecular basis of disease determine

A

the molecular factors that underly the causes and progression of diseases

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34
Q

what are some general health issues that are heavily related to the oral cavity

A

chronic kidney disease
diabetes
cardiovascular diseases
autoimmune diseases

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35
Q

how do our cells communicate

A

via signalling pathways

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36
Q

what do signalling pathways enable cells to do

A

detect and respond to changes in the environment and allow cells to coordinate their responses

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37
Q

what are ligands

A

chemical signals that deliver information about the activites of one cell and communicate them to another

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38
Q

what are the four categories of cell signalling

A

paracrine
autocrine
endocrine
close contact

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39
Q

what is paracrine signalling

A

when a cell targets a nearby cell of a different type

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40
Q

what is endocrine signalling

A

when a cell targets a distant cell through the bloodstream

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41
Q

what is autocrine signalling

A

where a cell targets itself or a cell of the same type locally

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42
Q

what is an example of contact dependent signalling

A

signalling across gap junctions

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43
Q

what is the main difference between all the ways cells can communicate with each other

A

the distance the ligand must travel to reach the target cell

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44
Q

which cell signalling types occur locally

A

paracrine and autocrine

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45
Q

which form of signalling is used if the ligand remains bound to the surface of the cell rather than being secreted

A

this would be contact dependent signalling as the two cell surface receptors would have to interact with each other

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46
Q
A
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47
Q

what is present on or within cells that recognise and bind ligands

A

protein receptors

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47
Q

what are the ligands in endocrine signalling

A

hormones

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48
Q

how can most signal molecules be described in relation to their affinity for the protein target receptors

A

most are large and hydrophilicPOLAR and therefore bind to the cell surface receptors rather than entering the cell

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49
Q

which ligands can bind to intracellular receptors

A

small hydrophobic ligands

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50
Q

what are receptors

A

proteins that bind to signalling molecules to initiate the signalling cascade

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51
Q

how many receptors are found in each individual cell

A

hundreds

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52
Q

why can hydrophilic ligands not enter the cell

A

the plasma membrane physically prevents them from entering. the membrane is based on a framework of fat based molecules called phospholipids with hydrophilic heads facing outward and hydrophobic tails on the inside. the hydrophobic tails prevent the hydrophilic substances from entering and escaping the cell

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53
Q

why are cell surface receptors required - why cant they all be intracellular

A

most ligands are hydrophilic and cannot enter the cell, so these can bind to the receptors and have their signal transmitted to the inside of the cell by the receptor

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54
Q

what happens in the absence of a ligand

A

no response, cell signalling pathway is switched off

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55
Q

what happens when a ligand binds to its receptor

A

it alters the shape or activity of the receptor which triggers a change on the inside of the cell

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56
Q

how do cell surface receptors lie on the plasma membrane

A

they span the membrane, with an extracellular part and an intracellular part

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57
Q

what happens when a ligand binds to its extracellular part of the receptor

A

conformational change in the activity and shape of the intracellular component of the receptor

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58
Q

how do receptors transmit their signal from the ligand once it has bound

A

change its conformation on the intracellular surface to transmit the signal

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59
Q

what feature of the receptor allows it to transmit the signal into the cell

A

its structure

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60
Q

what happens once there is a conformational change on the inner portion of the receptor

A

a series of biochemical events within the cell is triggered

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61
Q

what are effector proteins

A

the final receiver of the message, and they are proteins that will initiate or effect some sort of response by the cell

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62
Q

what is the final stage of cell communication

A

cell response - the effector proteins might be proteins that are in the cytoplasm of the cell, meaning the cell would be to tell particular enzymes to switch on or off, or the effector protiens could be in the nucleus where it may bring about changes in gene expression

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63
Q

what does the nature of cell response to signalling depend on

A

interpretation of the message that is delivered by the ligand

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64
Q

what are the three distinct stages of cell signalling pathways

A

receptor ligation
signal transduction
cell response

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65
Q

how can ligand receptor interactions be described

A

highly specific

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66
Q

what are the three classes of receptors

A

g protein coupled receptors
enzyme linked receptors
ion channel receptors

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67
Q

what are intracellular receptors

A

receptors present within the cell

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68
Q

which receptors will insulin bind to

A

only insulin receptors

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69
Q

which receptors will acetylcholine bind to

A

acetylcholine receptors which are present on the surface of skeletal and cardiac muscle cell, which both have different responses

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70
Q

what are the responses of the acetylcholine receptors on the cardiac muscle cells once acetylcholine has bound

A

reduce the force and rate of contraction

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71
Q

what are the responses of the receptors for acetylcholine on skeletal muscle cells

A

intitiations of the sliding filament contraction

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72
Q

what is an example of receptors that can bind to a few different ligands

A

adrenergic receptors which can bind to both adrenaline and noradrenaline, although noradrenaline only binds to beta adrenergic receptors

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73
Q

how do g protein receptors receive their message

A

via the action of g proteins

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74
Q

how do enzyme coupled receptors receive their message

A

enzymatic activity

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75
Q

how do ion channel receptors receive their message

A

ion channel opening

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76
Q

how are the different cell surface receptors named

A

according to the mechanisms by which they convert the signal into an intracellular signal

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77
Q

what is an example of signalling molecules that can enter the cell and bind to intracellular receptors

A

steroid hormones

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78
Q

describe g protein coupled receptors

A

the largest and most diverse group of membrane receptors that interact with g proteins.
the active g proteins activate cell membrane proteins

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79
Q

how many different g protein coupled receptors are there

A

1000

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80
Q

what proportion of FDA approved drugs target the g protein coupled receptors

A

34%

81
Q

describe the structure of g protein coupled receptors

A

single protein chain that is folded and embedded into the cells plasma membrane. crosses the membrane seven times

82
Q

what do GPCR associate with and bind to in the absence of a ligand

A

GDP

83
Q

when are GPCR bound to GDP

A

in the absence of a ligand

84
Q

give an example of a cell signalling pathway involved g protein coupled receptors

A
  • GPCR bound to GDP
  • adrenaline binds
  • conformational change on the intracellular component
  • intracellular affinity changes from GDP to GTP
  • GTP interacts with adenylyl cyclase to make cyclic AMP using ATP
85
Q

what are GPCR often involved in

A

growth, metabolism and homeostasis

86
Q

describe enzyme coupled receptors

A

these are receptors with intrinsic enzyme activity. when the ligand binds to the extracellular component of these receptors, the enzymatic activity on the intracellular component is activated

87
Q

what is the largest family of enzyme coupled receptors

A

receptor tyrosine kinases

88
Q

which enzymes add phosphate groups to proteins

A

protein kinases

89
Q

which enzymes remove phosphate groups from proteins

A

protein phosphotases

90
Q

describe the cell signalling pathway of tyrosine kinase receptors

A

add phosphate to tyrosine residues and other proteins in the cell when there is a ligand binding event which changes their conformation and can turn the proteins either on or off

91
Q

describe the autocrine signalling of immune cells

A

once immune cells are activated and directed towards the site of damage/infection, they in turn start to produce and release pro-inflammatory mediators, which has the effect to reinforce the activation and pro-inflammatory function of those same immune cells

92
Q

describe ion channel receptors

A

these convert chemical messages into electrical messages, and are ligand and voltage gated

93
Q

what are ion channel receptors important for

A

neuronal and muscular action potentials

94
Q

what is lidocaine

A

an anaesthetic that blocks the activity of a neuronal action potential by binding to and blocking the activity of voltage gated sodium channels to prevent the pain signals being delivered

95
Q

which forms can ion channel receptors come in

A

both ligand and voltage gated

96
Q

describe the function of ligand gated ion channels

A

the activity of the channel is determined by ligand binding. receptors are ligand gated, and when they bind to the ligand they open and ions pour into the cell

97
Q

describe the events when acetylcholine binds to its ligand gated receptor

A

it opens the ion channel and sodium ions enter the cell
the voltage gated ion channels on the sarcoplasmic reticulum detect the influx of sodium and open
the voltage gated receptors allow calcium to come our of the SR and trigger contraction by the sliding filament mechanism

98
Q

what effect does receptor ligation have on the intracellular domain

A

it causes it to change shape

99
Q

what are the sets of biochemical reactions that take place in the cell actually called

A

signal transduction cascades

100
Q

what are second messengers

A

small non protein molecules

101
Q

what does phosphorylation do to proteins

A

modifies its activity

102
Q

how are action potentials mediated

A

ion influx

103
Q

what is a common second messenger

A

cyclic AMP

104
Q

how is cAMP formed

A

it is converted from ATP by active adenylyl cyclase

105
Q

what does cAMP function to do

A

activate protein kinase A

106
Q

what is the effect of cAMP

A

changes in gene expression via the activation of transcription factors

107
Q

what can initiate the production of cAMP

A

activation of g protein coupled receptors which then trigger through GTP the activation of another cell membrane protein called adenylyl cyclase

108
Q

what can cAMP generate

A

hundreds of molecules of cyclic AMP which can then activate protein kinase A which phosphorylates multiple protein substrates

109
Q

describe the journey protein kinase A follows once activated

A

travels from the cytoplasm into the nucleus to activate transcriptional regulators that function to regulate the pattern of gene expression within the cell

110
Q

what are the steps to a phosphorylation cascade

A

one kinase phosphorylates the next one to continue the message onward and spread it to other signalling pathways

111
Q

how can phosphorylation cascades be intitiated

A

directly from the cell surface receptor.

112
Q

what do the intracellular biochemical reactions do

A

amplify the signal and deliver the signal to effector proteins

113
Q

how many intracellular signal transduction molecules are activated by one receptor

A

hundreds

114
Q

what does cell communication ultimately lead to

A

regulation of cell responses

115
Q

what can the final target molecule be if not an effector protein

A

transcription factor that binds DNA to regulate gene transcription

116
Q

how do cells change their behaviour

A

regulating protein translation

117
Q

what are each of our cells programmed to respond to

A

a specific set of cell signals

118
Q

what are diseases involved in the breakdown of

A

cellular communication

119
Q

what are the different ways that cellular communication can be broken down

A

loss of the signal
failure to respond to a signal
failure of a signal to reach the target cell
over or under expression of the signal

120
Q

can multiple breakdowns occur in a single disease

A

yes. a disruption in one signalling pathway can have consequences for other pathways.

121
Q

what can damage to neurons prevent

A

the signal reaching its target cells

122
Q

what do cells have tight controls of

A

whether they will differentiate or not

123
Q

describe type one diabetes

A

the signal is lost.
immune system attacks and destroys the beta cells in the pancreas responsible for producing insulin, which leads to no uptake of glucose into the cells, and an accumulation of glucose in the bloodstream

124
Q

what is the normal pathway for insulin signalling

A

food enters the body
broken down
sugar enters bloodstream
sugar stimulates cells in the pancreas to release insulin
insulin travels through the blood to other cells in the body and signals them to take up sugar
glucose receptors in the pancreas detect the rising levels of glucose and respond via insulin release
when insulin binds the cells may begin to take up glucose from the blood

125
Q

what does uptake of glucose help to maintain

A

levels of glucose in the blood within homeostatic limits

126
Q

what happens if the pathway for insulin is switched off

A

the cells cant receive the glucose and there is accumulation of glucose in the blood which is bad for the cardiovascular system

127
Q

what is the treatment option for type one diabetes

A

insulin replacement therapy to restore the function of the pathway to maintain blood glucose within its healthy limits. not a cure

128
Q

describe type two diabetes

A

the target cells ignore the signal and is associated with poor diet.
the pancreas still releases insulin when there are higher levels of glucose detected in the blood. if eating is frequent and the blood glucose is high for a prolonged period of time, the pathway can become desensitised to sustained signalling and switch off
the cells are full of glucose and dont want any more so they just turn off and the glucose will accumulate in the blood at high levels

129
Q

what is the treatment option for type 2 diabetes

A

diet and exercise can help to regulate blood glucose
when the cell wants to turn off its insulin receptor, it uses tyrosine phosphotase to dephosphorylate the receptors and prevent the signal being transduced. metformin can be used to inhibit the tyrosine phosphotase and stop it from turning the receptor off to restore the function of the pathway. this helps to increase insulin receptor expression and get more insulin expression on the cell

130
Q

how do eptihelial cells trigger an immune response

A

receptors on the cell surface can detect cell damage and microbial products.
cell responds by activating transcription factor NFkB which activates transcription of genes encoding pro inflammatory mediators like cytokines and antimicrobial peptides.
these mediators are released by the cells into the extracellular enviroment where they communicate the damage or infection to immune cells
these respond by infiltrating the tissue and clearing the infection

131
Q

what are the similarities between type one and type two diabetes

A

the same pathway is affected, and the disease outcome is the same whereby high levels of glucose accumulate in the blood

132
Q

what are the differences between type one and type two diabetes

A

their moleculer basis is different and requires different treatment - there is no insulin signal in type one and no response in type two

133
Q

describe the molecular basis of therapeutics

A

drugs must interact chemically with a target to induce a therapeutic effect and this is done by binding proteins in the cell membrane to induce a cellular response

134
Q

what does autocrine signalling reinforce

A

activation signals of responding immune cells and their pro inflammatory function

135
Q

what do intercalated discs contain

A

gap junctions which allow signalling molecules to move betwen adjacent cells

136
Q

what must be present to allow signalling molecules to move between adjacent cells

A

gap junctions

137
Q

what do individual haploids secrete when they are ready to mate

A

a peptide mating factor which signals cells of the opposite mating type to stop proliferating and prepare to mate

138
Q

how do yeast cells communicate with one another for mating

A

by secreting a few kinds of small peptides.

139
Q

what are some examples of signal molecules

A

proteins
small peptides
amino acids
nucleotides
steroids
retinoids
fatty acid derivatives
nitric oxide
carbon monoxide

140
Q

how do target cells respond

A

by means of a specific protein called a receptor, which binds to the signal molecule and intitiates a response in the target cell.

141
Q

at which concentations to extracellular signalling molecules act at

A

very low concentrations

142
Q

what must be signal molecule be in order to enter the cell and bind to its receptor

A

sufficiently small and hydrophobic

143
Q

what is contact dependent signalling

A

this is when some signal moleceules remain bound to the surface and influence only the cells that contact it

144
Q

when is contact dependent signalling important

A

during development and in immune responses

145
Q

what must the secreted molecules in paracrine signalling do

A

not diffuse too far

146
Q

what can happen to ensure paracrine signalling molecules do not diffuse too far

A
  • be rapidly taken up by neighboring target cells
  • destroyed by extracellular enzymes
  • immobilised by the extracellular matrix
147
Q

why is endocrine signalling relatively slow

A

it relies on diffusion and blood flow

148
Q

why must hormones be able to act at low concentrations

A

they are diluted in the bloodstream and interstitial fluid

149
Q

why are neurotransmitters able to achieve high concentrations

A

they are diluted much less

150
Q

the neurotransmitter ligands have a relatively low affinity for their ligand. what does this mean

A

the neurotransmitters can dissociate rapidly from the receptor to terminate a response

151
Q

does changes in gene expression take more or less time compared to changes in the proteins of the cell

A

more time

152
Q

how do gap junctions allow for the movement of intracellular signalling molecules between adjacent cells

A

they directly connect the cytoplasms of joint cells via narrow water filled channels to allow the exchange of small intracellular signalling molecules like calcium or cyclic AMP, but not proteins or nucleic acids

153
Q

can proteins and nucleic acids diffuse through gap junctions

A

no

154
Q

what are the different ways a cell could respond to a combination of signals

A

differentiation, multiplying, performing some specialised functions like contraction or secretion

155
Q

what are intracellular signalling molecules

A

those that are small and hydrophobic and can readily pass across the target cell’s plasma membrane to directly regulate the activity of a specific intracellular protein

156
Q

how does nitric oxide behave as a signal molecule

A

regulates smooth muscle contraction.

157
Q

how do acetylcholine and nitric oxide coincide

A

acetylcholine is released by autonomic nerves in the walls of the blood vessel and cause smooth muscle cells in the vessel to relax. can induce nearby endothelial cells to make and release nitric oxide which signals the underlying smooth muscle cells to relax

158
Q

what are some examples of intracellular signalling molecules

A

steroid hormones
thyroid hormones
retinoids
vitamin D

159
Q

what happens when intracellular signalling molecules bind to their receptor proteins

A

they activate the receptors which bind to DNA to regulate the transcription of specific genes

160
Q

what are some examples of steroid hormones

A

cortisol and steroid sex hormones

161
Q

what are steroid hormones made of

A

cholesterol

162
Q

where is cortisol produced

A

in the cortex of adrenal glands

163
Q

what does cortisol do

A

influences the metabolism of many types of cells

164
Q

what are thyroid hormones made from

A

the amino acid tyrosine

165
Q

what are retinoids made from

A

vitamin A

166
Q

how do hydrophobic and hydrophilic signal molecules differ

A

in the length of time they persist in the bloodstream or tissue fluids

167
Q

do hydrophilic hormones remain in the blood for a long time

A

no they are removed or broke down within minutes of entering

168
Q

how long do steroid hormones remain in the blood

A

hours

169
Q

how long do thyroid hormone remain in the blood

A

days

170
Q

are the effects of hydrophilic or hydrophobic signalling molecules longer

A

hydrophobic

171
Q

how does ligand binding in the intracellular receptors cause a response

A

inactive receptors are bound to inhibitory protein complexes and ligand binding alters their conformation, causing the inhibitory complex to dissociate
ligand binding causes the receptor to bind to coactivator proteins that induce gene transcription

172
Q

when can an intracellular receptor activate a gene

A

when there is the right combination of other gene regulatory proteins which are cell type specific

173
Q

what are g proteins

A

trimeric gtp binding proteins

174
Q

how many times do enzyme coupled receptors pass the membrane

A

once

175
Q

how many second messengers are produced in response to receptor activation

A

large numbers are produced and they rapidly diffuse away from their source to broadcast the signal to other parts of the cell

176
Q

what are some different intracellular signalling proteins

A

relay proteins
messenger proteins
adaptor proteins
amplifier proteins
transducer proteins
bifurcation proteins
integrator proteins
latent gene regulatory proteins

177
Q

what do messenger proteins do

A

carry the signal from one part of the cell to another such as from the cytosol to the nucleus

178
Q

what do relay proteins do

A

pass the message to the next signalling component in the chain

179
Q

what do adaptor proteins do

A

link one signalling protein to another without conveyed a signal themselves

180
Q

what do amplifier proteins do

A

increase the signal received by produceign large amounts of small itracellular mediators or by activating large numbers of downstream intracellular signalling proteins. ie cause a signalling cascade. usually enzymes or ion channels

181
Q

what are transducer proteins

A

proteins that convert the signal into a different form

182
Q

what do birfurcation proteins do

A

they spread the signal from one signalling pathway to another

183
Q

what do integrator proteins do

A

receive signals from two or more signalling pathways and integrate them before relayed the signal onward

184
Q

what are latent gene regulatory proteins

A

proteins that are activated at the cell surface by activated receptors and then migrate to the nucleus to stimulate gene transcription

185
Q

what do many intracellular signalling proteins behave as

A

molecular switches, which switch from an inactive state to an active one on receipt of a signal.

186
Q

what are the two main types of protein kinases

A

serine/ threonine kinases
tyrosine kinase

187
Q

what do serine kinases do

A

phosphorylate proteins on serine

188
Q

what do tyrosine kinases do

A

phosphorylate proteins on tyrosine

189
Q

what are GTP binding proteins

A

another class of molecular swithces which switch between an active state when the GTP is bound and an inactive state when the GDP is bound

190
Q

what are examples of GTP binding proteins

A

g proteins and monomeric GTP binding proteins

191
Q

what are scaffold proteins

A

proteins that acheive specifity by organising groups of interacting signalling proteins into signalling complexes. the scaffold guides the interactions between successive components in a complex and the signal can be relayed with precision speed and efficiency

192
Q

what is the link between concentration of hormone and concentration of activated receptor hormone complexes

A

the increase in A increases B

193
Q

do the effects of extracellular signals on target cells disappear alongside the signal

A

no they can persist long agter

194
Q

how is centralised control exerted

A

by endocrine signalling and by synaptic signalling

195
Q

what is an example of paracrine signalling

A

nerve impulses at a synapse

196
Q

what is an example of autocrine signalling

A

cancer proliferation

197
Q

what is an example of endocrine signalling

A

estrogen

198
Q

what is an example of juxtacrine signalling

A

adjacent epithelial cells

199
Q
A

Molecules and Cells (13 decks)

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