Molecular Basis of Health and Disease Flashcards
1
Q
what are the different systems within the body
A
nervous
respiratory
circulatory
digestive
2
Q
what does the nervous system do
A
allow us to receive and respond to our environment
3
Q
what does the respiratory system do
A
breathe and take up oxygen and expel carbon dioxide
4
Q
what does the circulatory system do
A
deliver oxygen and nutrients throughout the body
5
Q
what does the digestive system do
A
extract energy and nutrients from food
6
Q
what are cells
A
functional units of life
7
Q
describe the structure of cells
A
each cell is a discrete package of material surrounded by plasma membrane
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
9
Q
is the cytoplasm thick
A
no it is watery
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
11
Q
what are some single celled organisms
A
protozoa and bacteria
12
Q
why do cells communicate
A
so they can respond to their environment
13
Q
how is cell communication achieved
A
through a network of signalling pathways essential for coordinated physiological responses
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
15
Q
what can disruption in cell communication pathways lead to
A
disruption of normal physiological processes leading to pathology
16
Q
what do the origins of disease emerge at the level of
A
cell communication pathways
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
18
Q
what are the levels to basis of health and disease
A
molecular
microscopic
macroscopic
environmental
19
Q
what is included in the molecular level of basis of health and disease
A
cell signalling, gene expression, protein expression
20
Q
what can changes in gene expression modify
A
cell behaviour
21
Q
what does the central dogma explain
A
essentially the process of dna becoming proteins through transcription and translation
22
Q
what acts as the structural and functional machinery of our cell
A
proteins
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.
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
25
what do cell communication pathways govern
our movements, thoughts and behaviours
26
what is involved at the microscopic level
cell structure and function
27
what is involved at the macroscopic level
tissues, organs, organ systems and their function
28
what is involved at the environmental level
chronic infection, dysbiosis, diet, physical inactivity, obesity, isolation, chronic stress, disturbed sleep and xenobiotics
29
what is the purpose of the environmental level of the basis of health and disease
look at how the environment can interact with our genes to modify our risk of disease
30
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
- chronic infection
- dysbiosis
- diet
- physical inactivity
- obesity
- isolation
- chronic stress
- disturbed sleep
- xenobiotics
31
what is an example of an environment factor and how it can affect the basis of health and disease
a diet high in carbohydrates will disrupt our glucose metabolic pathways in our cells and predispose us to type two diabetes
32
what is ateology
the cause of pathogenesis
33
what does the molecular basis of disease determine
the molecular factors that underly the causes and progression of diseases
34
what are some general health issues that are heavily related to the oral cavity
chronic kidney disease
diabetes
cardiovascular diseases
autoimmune diseases
35
how do our cells communicate
via signalling pathways
36
what do signalling pathways enable cells to do
detect and respond to changes in the environment and allow cells to coordinate their responses
37
what are ligands
chemical signals that deliver information about the activites of one cell and communicate them to another
38
what are the four categories of cell signalling
paracrine
autocrine
endocrine
close contact
39
what is paracrine signalling
when a cell targets a nearby cell of a different type
40
what is endocrine signalling
when a cell targets a distant cell through the bloodstream
41
what is autocrine signalling
where a cell targets itself or a cell of the same type locally
42
what is an example of contact dependent signalling
signalling across gap junctions
43
what is the main difference between all the ways cells can communicate with each other
the distance the ligand must travel to reach the target cell
44
which cell signalling types occur locally
paracrine and autocrine
45
which form of signalling is used if the ligand remains bound to the surface of the cell rather than being secreted
this would be contact dependent signalling as the two cell surface receptors would have to interact with each other
46
47
what is present on or within cells that recognise and bind ligands
protein receptors
47
what are the ligands in endocrine signalling
hormones
48
how can most signal molecules be described in relation to their affinity for the protein target receptors
most are large and hydrophilicPOLAR and therefore bind to the cell surface receptors rather than entering the cell
49
which ligands can bind to intracellular receptors
small hydrophobic ligands
50
what are receptors
proteins that bind to signalling molecules to initiate the signalling cascade
51
how many receptors are found in each individual cell
hundreds
52
why can hydrophilic ligands not enter the cell
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
53
why are cell surface receptors required - why cant they all be intracellular
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
54
what happens in the absence of a ligand
no response, cell signalling pathway is switched off
55
what happens when a ligand binds to its receptor
it alters the shape or activity of the receptor which triggers a change on the inside of the cell
56
how do cell surface receptors lie on the plasma membrane
they span the membrane, with an extracellular part and an intracellular part
57
what happens when a ligand binds to its extracellular part of the receptor
conformational change in the activity and shape of the intracellular component of the receptor
58
how do receptors transmit their signal from the ligand once it has bound
change its conformation on the intracellular surface to transmit the signal
59
what feature of the receptor allows it to transmit the signal into the cell
its structure
60
what happens once there is a conformational change on the inner portion of the receptor
a series of biochemical events within the cell is triggered
61
what are effector proteins
the final receiver of the message, and they are proteins that will initiate or effect some sort of response by the cell
62
what is the final stage of cell communication
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
63
what does the nature of cell response to signalling depend on
interpretation of the message that is delivered by the ligand
64
what are the three distinct stages of cell signalling pathways
receptor ligation
signal transduction
cell response
65
how can ligand receptor interactions be described
highly specific
66
what are the three classes of receptors
g protein coupled receptors
enzyme linked receptors
ion channel receptors
67
what are intracellular receptors
receptors present within the cell
68
which receptors will insulin bind to
only insulin receptors
69
which receptors will acetylcholine bind to
acetylcholine receptors which are present on the surface of skeletal and cardiac muscle cell, which both have different responses
70
what are the responses of the acetylcholine receptors on the cardiac muscle cells once acetylcholine has bound
reduce the force and rate of contraction
71
what are the responses of the receptors for acetylcholine on skeletal muscle cells
intitiations of the sliding filament contraction
72
what is an example of receptors that can bind to a few different ligands
adrenergic receptors which can bind to both adrenaline and noradrenaline, although noradrenaline only binds to beta adrenergic receptors
73
how do g protein receptors receive their message
via the action of g proteins
74
how do enzyme coupled receptors receive their message
enzymatic activity
75
how do ion channel receptors receive their message
ion channel opening
76
how are the different cell surface receptors named
according to the mechanisms by which they convert the signal into an intracellular signal
77
what is an example of signalling molecules that can enter the cell and bind to intracellular receptors
steroid hormones
78
describe g protein coupled receptors
the largest and most diverse group of membrane receptors that interact with g proteins.
the active g proteins activate cell membrane proteins
79
how many different g protein coupled receptors are there
1000
80
what proportion of FDA approved drugs target the g protein coupled receptors
34%
81
describe the structure of g protein coupled receptors
single protein chain that is folded and embedded into the cells plasma membrane. crosses the membrane seven times
82
what do GPCR associate with and bind to in the absence of a ligand
GDP
83
when are GPCR bound to GDP
in the absence of a ligand
84
give an example of a cell signalling pathway involved g protein coupled receptors
- 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
what are GPCR often involved in
growth, metabolism and homeostasis
86
describe enzyme coupled receptors
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
what is the largest family of enzyme coupled receptors
receptor tyrosine kinases
88
which enzymes add phosphate groups to proteins
protein kinases
89
which enzymes remove phosphate groups from proteins
protein phosphotases
90
describe the cell signalling pathway of tyrosine kinase receptors
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
describe the autocrine signalling of immune cells
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
describe ion channel receptors
these convert chemical messages into electrical messages, and are ligand and voltage gated
93
what are ion channel receptors important for
neuronal and muscular action potentials
94
what is lidocaine
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
which forms can ion channel receptors come in
both ligand and voltage gated
96
describe the function of ligand gated ion channels
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
describe the events when acetylcholine binds to its ligand gated receptor
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
what effect does receptor ligation have on the intracellular domain
it causes it to change shape
99
what are the sets of biochemical reactions that take place in the cell actually called
signal transduction cascades
100
what are second messengers
small non protein molecules
101
what does phosphorylation do to proteins
modifies its activity
102
how are action potentials mediated
ion influx
103
what is a common second messenger
cyclic AMP
104
how is cAMP formed
it is converted from ATP by active adenylyl cyclase
105
what does cAMP function to do
activate protein kinase A
106
what is the effect of cAMP
changes in gene expression via the activation of transcription factors
107
what can initiate the production of cAMP
activation of g protein coupled receptors which then trigger through GTP the activation of another cell membrane protein called adenylyl cyclase
108
what can cAMP generate
hundreds of molecules of cyclic AMP which can then activate protein kinase A which phosphorylates multiple protein substrates
109
describe the journey protein kinase A follows once activated
travels from the cytoplasm into the nucleus to activate transcriptional regulators that function to regulate the pattern of gene expression within the cell
110
what are the steps to a phosphorylation cascade
one kinase phosphorylates the next one to continue the message onward and spread it to other signalling pathways
111
how can phosphorylation cascades be intitiated
directly from the cell surface receptor.
112
what do the intracellular biochemical reactions do
amplify the signal and deliver the signal to effector proteins
113
how many intracellular signal transduction molecules are activated by one receptor
hundreds
114
what does cell communication ultimately lead to
regulation of cell responses
115
what can the final target molecule be if not an effector protein
transcription factor that binds DNA to regulate gene transcription
116
how do cells change their behaviour
regulating protein translation
117
what are each of our cells programmed to respond to
a specific set of cell signals
118
what are diseases involved in the breakdown of
cellular communication
119
what are the different ways that cellular communication can be broken down
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
can multiple breakdowns occur in a single disease
yes. a disruption in one signalling pathway can have consequences for other pathways.
121
what can damage to neurons prevent
the signal reaching its target cells
122
what do cells have tight controls of
whether they will differentiate or not
123
describe type one diabetes
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
what is the normal pathway for insulin signalling
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
what does uptake of glucose help to maintain
levels of glucose in the blood within homeostatic limits
126
what happens if the pathway for insulin is switched off
the cells cant receive the glucose and there is accumulation of glucose in the blood which is bad for the cardiovascular system
127
what is the treatment option for type one diabetes
insulin replacement therapy to restore the function of the pathway to maintain blood glucose within its healthy limits. not a cure
128
describe type two diabetes
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
what is the treatment option for type 2 diabetes
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
how do eptihelial cells trigger an immune response
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
what are the similarities between type one and type two diabetes
the same pathway is affected, and the disease outcome is the same whereby high levels of glucose accumulate in the blood
132
what are the differences between type one and type two diabetes
their moleculer basis is different and requires different treatment - there is no insulin signal in type one and no response in type two
133
describe the molecular basis of therapeutics
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
what does autocrine signalling reinforce
activation signals of responding immune cells and their pro inflammatory function
135
what do intercalated discs contain
gap junctions which allow signalling molecules to move betwen adjacent cells
136
what must be present to allow signalling molecules to move between adjacent cells
gap junctions
137
what do individual haploids secrete when they are ready to mate
a peptide mating factor which signals cells of the opposite mating type to stop proliferating and prepare to mate
138
how do yeast cells communicate with one another for mating
by secreting a few kinds of small peptides.
139
what are some examples of signal molecules
proteins
small peptides
amino acids
nucleotides
steroids
retinoids
fatty acid derivatives
nitric oxide
carbon monoxide
140
how do target cells respond
by means of a specific protein called a receptor, which binds to the signal molecule and intitiates a response in the target cell.
141
at which concentations to extracellular signalling molecules act at
very low concentrations
142
what must be signal molecule be in order to enter the cell and bind to its receptor
sufficiently small and hydrophobic
143
what is contact dependent signalling
this is when some signal moleceules remain bound to the surface and influence only the cells that contact it
144
when is contact dependent signalling important
during development and in immune responses
145
what must the secreted molecules in paracrine signalling do
not diffuse too far
146
what can happen to ensure paracrine signalling molecules do not diffuse too far
- be rapidly taken up by neighboring target cells
- destroyed by extracellular enzymes
- immobilised by the extracellular matrix
147
why is endocrine signalling relatively slow
it relies on diffusion and blood flow
148
why must hormones be able to act at low concentrations
they are diluted in the bloodstream and interstitial fluid
149
why are neurotransmitters able to achieve high concentrations
they are diluted much less
150
the neurotransmitter ligands have a relatively low affinity for their ligand. what does this mean
the neurotransmitters can dissociate rapidly from the receptor to terminate a response
151
does changes in gene expression take more or less time compared to changes in the proteins of the cell
more time
152
how do gap junctions allow for the movement of intracellular signalling molecules between adjacent cells
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
can proteins and nucleic acids diffuse through gap junctions
no
154
what are the different ways a cell could respond to a combination of signals
differentiation, multiplying, performing some specialised functions like contraction or secretion
155
what are intracellular signalling molecules
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
how does nitric oxide behave as a signal molecule
regulates smooth muscle contraction.
157
how do acetylcholine and nitric oxide coincide
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
what are some examples of intracellular signalling molecules
steroid hormones
thyroid hormones
retinoids
vitamin D
159
what happens when intracellular signalling molecules bind to their receptor proteins
they activate the receptors which bind to DNA to regulate the transcription of specific genes
160
what are some examples of steroid hormones
cortisol and steroid sex hormones
161
what are steroid hormones made of
cholesterol
162
where is cortisol produced
in the cortex of adrenal glands
163
what does cortisol do
influences the metabolism of many types of cells
164
what are thyroid hormones made from
the amino acid tyrosine
165
what are retinoids made from
vitamin A
166
how do hydrophobic and hydrophilic signal molecules differ
in the length of time they persist in the bloodstream or tissue fluids
167
do hydrophilic hormones remain in the blood for a long time
no they are removed or broke down within minutes of entering
168
how long do steroid hormones remain in the blood
hours
169
how long do thyroid hormone remain in the blood
days
170
are the effects of hydrophilic or hydrophobic signalling molecules longer
hydrophobic
171
how does ligand binding in the intracellular receptors cause a response
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
when can an intracellular receptor activate a gene
when there is the right combination of other gene regulatory proteins which are cell type specific
173
what are g proteins
trimeric gtp binding proteins
174
how many times do enzyme coupled receptors pass the membrane
once
175
how many second messengers are produced in response to receptor activation
large numbers are produced and they rapidly diffuse away from their source to broadcast the signal to other parts of the cell
176
what are some different intracellular signalling proteins
relay proteins
messenger proteins
adaptor proteins
amplifier proteins
transducer proteins
bifurcation proteins
integrator proteins
latent gene regulatory proteins
177
what do messenger proteins do
carry the signal from one part of the cell to another such as from the cytosol to the nucleus
178
what do relay proteins do
pass the message to the next signalling component in the chain
179
what do adaptor proteins do
link one signalling protein to another without conveyed a signal themselves
180
what do amplifier proteins do
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
what are transducer proteins
proteins that convert the signal into a different form
182
what do birfurcation proteins do
they spread the signal from one signalling pathway to another
183
what do integrator proteins do
receive signals from two or more signalling pathways and integrate them before relayed the signal onward
184
what are latent gene regulatory proteins
proteins that are activated at the cell surface by activated receptors and then migrate to the nucleus to stimulate gene transcription
185
what do many intracellular signalling proteins behave as
molecular switches, which switch from an inactive state to an active one on receipt of a signal.
186
what are the two main types of protein kinases
serine/ threonine kinases
tyrosine kinase
187
what do serine kinases do
phosphorylate proteins on serine
188
what do tyrosine kinases do
phosphorylate proteins on tyrosine
189
what are GTP binding proteins
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
what are examples of GTP binding proteins
g proteins and monomeric GTP binding proteins
191
what are scaffold proteins
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
what is the link between concentration of hormone and concentration of activated receptor hormone complexes
the increase in A increases B
193
do the effects of extracellular signals on target cells disappear alongside the signal
no they can persist long agter
194
how is centralised control exerted
by endocrine signalling and by synaptic signalling
195
what is an example of paracrine signalling
nerve impulses at a synapse
196
what is an example of autocrine signalling
cancer proliferation
197
what is an example of endocrine signalling
estrogen
198
what is an example of juxtacrine signalling
adjacent epithelial cells
199
