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Cell physiology and pathology Flashcards

1
Q

What are the roles of the plasma membrane?

A

-Physical barrier- Protect and support cell structure
-Selective permeability- regulates exit&entry of ions, nutrients, waste
-Electrochemical gradients- Maintain charge
-Communication- contains receptors- respond to signals

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2
Q

Explain the structure of the plasma membrane.

A

-Mainly phospholipids- hydrophilic parts face outwards, hydrophobic inwards->
Forms lipid bilayer- fluid and dynamic structure with proteins floating through lipids (fluid mosaic model)

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3
Q

What are the functions of the following membrane proteins:
Structural?
Receptor?
Channel?
Transport?
Glycoproteins?

A
  • Structural proteins help to give the cell support and shape.
  • Receptor proteins help cells communicate with their external environment
    via hormones, neurotransmitters etc
  • Channel proteins serve to allow water, ions and proteins to flow passively
    through the bilayer
  • Transport proteins transport molecules across cell membranes
  • Glycoproteins have a carbohydrate chain attached to them. They are
    embedded in the cell membrane and help in cell to cell communications and
    adhesion
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4
Q

How do hydrophobic and hydrophilic substances pass the membrane?

A

Hydrophobic- passive diffusion
Hydrophilic- Transport using protein carriers

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5
Q

What specialised proteins help water cross the membrane?

A

Aquaporins

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6
Q

Explain passive diffusion.

A

High to low conc, no energy required

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7
Q

Explain active transport.

A

Movement from low to high conc using energy (from ATP) against conc gradient using protein carriers/channels

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8
Q

What happens to a cell that is exposed to a hypertonic solution?

A

Shrink due to osmotic water loss, cytoplasmic components become more concentrated

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9
Q

What happens to a cell that is exposed to a hypotonic solution?

A

Swell due to osmotic water influx- cytoplasmic components become more dilute

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10
Q

How do ions cross the membrane and what determines the permeability to ions?

A

Diffuse across via specialised proteins that form “ion channels”
permeability to different ions determined by number of ion channels that are open

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11
Q

How does the NA-K pump work?

A

-Na-K pump is an enzyme that hydrolyses ATP- consumes energy to do work
-Transports Na+ out of cell in exchange for K+
-Energy from ATP used to transport against concentration gradient (Active transport)

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12
Q

What is the concentration of ions like in the cytoplasm compared with then extracellular fluid?

A

[Na+]- low in cytoplasm- high in extracellular fluid
[K+]- high in cytoplasm- low in extracellular fluid

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13
Q

why can it be said that there is a inwardly-directed, chemical driving force on Na+ ?

A

Na-K pump establishes and maintains an inwardly directed conc gradient for Na+
-the conc of Na+ outside the cell is higher than inside the cell so therefore wants to go down the conc gradient (chemical driving force)

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14
Q

why can it be said that there is an inwardly- directed electrical driving force on Na+ ?

A

-All animal cells have a resting potential
-Inside slightly more positive than outside
-Na+ is +ve so attracted to the inside of the cell (electrical driving force)

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15
Q

What is the overall driving force on Na+?

A

Electrochemical

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16
Q

There is always a large electrochemical driving force on Na+, what barrier stops Na+ from entering the cell and how does it overcome this?

A

Plasma membrane has a low permeability to Na+ so has to access a source of potential energy.

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17
Q

What does the large electrochemical force on Na+ provide?

A

-Provides a source of potential energy that allows cells to intake sugars/amino aicds.

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18
Q

What is the chemical and electrical driving force on K+?

A

Chemical=outwardly directed as Na+ pump maintains high internal [K+]
Electrical= inwardly directed as K+ is +ve and cell=-ve

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19
Q

Why is the electrochemical force of K+ smaller than the force on Na+?

A

Because the chemical and electrical driving forces that act on K+ have opposite polarity

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20
Q

What direction is the net electrochemical force that acts on K+?

A

Outwardly directed

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21
Q

How is Ca2+ extruded from the cytoplasm?

A

Ca2+ pump- active transport

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22
Q

Which way is the chemical and electrical gradient directed for Ca2+?

A

inward (even larger than Na+)
->again plasma membrane normally very impermeable to Ca2+

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23
Q

What has to happen before Na+/Ca2+ enter the cell?

A

Activation of receptors allow Na/Ca2+ to cross the membrane and therefore generate a cellular response

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24
Q

What are the three stages of signal transduction?

A
  1. An extracellular signal molecule activates a membrane receptor
  2. Intracellular molecules become transduced via a certain pathway
    3.Activates a cellular response
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25
In signal transduction what is classes as the "first messenger" and what forms the "second messenger system"?
Extracellular signal molecule= first messenger Intracellular molecules form the second messenger system
26
What are transducers?
Membrane proteins
27
What are some examples of first messengers?
Amines, Peptides & Proteins, Steroids, Other small molecules e.g. amino acids, ions, gases.
28
What are the 4 main classes of receptors?
1. Ligand-gated ion channels 2. G-protein coupled receptors 3.Enzyme-linked receptors 4.Nuclear receptors
29
How does the binding of acetyl choline to an Ionotropic receptor lead to a response?
-Acetylcholine binds to the receptor causing a channel to open and Na+ to enter -Binds nicotin -Electrical event (inward Na+ current) triggers response -Calcium may also enter from this channel causing muscle contraction
30
What type of receptor is the y-amino buytyric acid (GABA)A receptor? What ions is it selective for?
Ionotropic- inhibitory receptor selective to cl- ions
31
What does metabotropic mean?
Indirectly linked with ion channels on the plasma membrane through signal transduction pathways
32
What are some examples of ionotropic receptors?
Nicotinic receptor GABA receptor
33
What are Ionotropic receptors?
Form an ion channel pore
34
What is an example of a metabotropic receptor?
Muscarinic
35
What are the ligand-gated ion receptors that acetylcholine can bind to?
Nicotinic and Muscarinic
36
What are the 3 polypeptide chains that G proteins consist of?
Alpha, Beta, Gamma
37
Why could you effectively say G proteins contain a BY subunit?
The B and Y subunits bind tightly to each other ... effectively forms a single BY subunit
38
What are the two compounds that the alpha subunit of a G-protein coupled receptor can bind to and why?
GTP or GDP because the alpha subunit contains a guanine nucleotide
39
What is the affinity for BY like for a-GDP and a-GTP?
a-GDP has a high affinity for BY (Resting conditions) a-GTP has low affinity for BY- a-subunit can hydrolyse GTP
40
Explain the G protein cycle. Use example of adrenaline.
1. Unstimulated cell 2.Adrenaline binding to the B-adrenoceptor 3.Allows B-adrenoceptor/G protein interaction 4.Allows GDP/GTP exchange 5.Allows a subunit liberation 6.Free subunit activates adenyl cyclase 7.Unbinding of adrenaline/GTP hydrolysis
41
What physiological responses are mediated by cAMP/PKA?
Kidney collecting duct- activated by vasopressin and stimulates water retention Vascular smooth muscle and Cardiac muscle- activated by adrenaline and promotes relaxation/increase heart rate Liver- activated by glucagone and promotes release of glucose in the blood
42
How is signal transduction terminated?
cAMP hydrolysed by phosphodiesterase (PDE) When hormone removed, PDE rapidly clear cAMP from cell Protein reassembles into tetramer and are inactivated PDEs are inhibited by caffeine, interfere with "switch off" mechanism so prolongs a cellular response as prevents PDE from removing cAMP
43
Explain Desensitization of a receptor.
1. Protein phosphorylation leads to cellular response 2. PKA phosphorylates B-adrenoceptor Kinase(B-ARK) and increases activity 3.B-ARK phosphorylates B-adrenoceptor and reduces affinity for adrenaline 4. Reduced affinity leads to reduced cellular response despite sustained stimulation Stops continuous action of receptor
44
Which of the two molecules can activate GPCRS? Adrenaline, Ach, cAMP, PKA.
Adrenaline, Ach
44
What can oppose the effects of PKA?
Protein phosphatases can remove the phosphate added by PKA to inactivate the protein
45
How many transmembrane domains do G-coupled protein receptors have?
7
46
What are the different types of G-protein coupled receptors? and what do they do regarding AC?
G-protein alpha s- stimulate adenylyl cyclase(AC) alpha i- inhibit AC Gq- don't couple to AC
47
Which G protein coupled receptor do B-adrenoreceptors and a2 adrenoreceptors couple to?
B-adrenoreceptors couple to Gs a2 adrenoreceptors couple to Gi
48
What enzyme are Gq proteins linked to?
Phospholipase C
49
What does Gq underline the autonomic effects of? Why?
Acetylcholine and Histamine H1 (Muscle contractions) Response due to the increased internal Ca2+
50
How do Gq proteins generate a response when activated?
-Activated by ligand (e.g. acetylcholine/histamine) -Stimulates phospholipid C which cleaves a PIP2 phospholipid from the cell membrane -Breaks PIP2 into diacylglycerol (DAG) and IP3 -DAG hydrophobic so remains in membrane and recruits protein kinase C (PKC) -IP3 is water soluble so can go into the cell to receptors on the ER which causes the release of stored Ca2+ -Ca2+ binds to Calmodulin (CAM) and forms a Ca2+-CAM complex -This activates CAM kinases and causes muscle contraction
51
Which G protein causes blood pressure to increase and how?
Gq protein because binds to the a1-adrenoreceptor via Gq-PLC-IP3, causing vasoconstriction
52
Which G protein causes blood pressure to decrease and how?
Gs binds to B2-adrenoreceptors via Gs-cAMP-PKA Causes vasodilation
53
How many types of muscarinic receptors are there and what do they do?
5 sub types underline autonomic effects of acetylcholine Inhibitory affect of adrenaline in the heart as acetylcholine is released and binds to Gi protein (Gi coupled receptor)
54
What receptor is coupled with Gi protein?
M2 muscarinic receptor
55
What is the difference between enzyme-linked receptors and G-coupled protein receptors?
The structure is different (2 transmembrane domain) and they bind to different enzymes
56
What are the 4 type of enzyme linked receptors?
A. Receptor guanylyl cyclases B. Receptor serine/threonine kinase C. Receptor tyrosine-kinase D. Receptor tyrosine phosphatase
57
Which enzyme does Receptor Guanylyl Cyclase and what does it do?
Guanylyl Cyclase convert GTP to cGMP activates kinases
58
What is the mechanism of signalling for receptor guanylyl cyclase? and give an example of the response.
1. Binding of ligand changes the receptor causes dimerization and activation 2. Guanylyl cyclase activity of receptor generates cGMP 3. Increased conc of cGMP activates signalling molecules 4. Response e.g. relax vascular smooth muscles causing vasodilation
59
What is the mechanism for receptor serine/threonine kinases?
-First messenger binds to receptor type II -Receptor type I binds forms a ternary complex with type II and first messenger -Type II phosphorylates Type I, activating Ser-Thr kinases activity -Phosphorylates target proteins Response- cell proliferation
60
Explain mechanism of signalling for Tyrosine Kinases. (RTK)
-Binding of insulin (ligand) causes receptor to dimerise -Activate tyrosine kinase -RTKs phosphorylates multiple tyrosines on other RTK -Recruit intracellular signalling molecules to create response Response- insulin mediated glucose uptake, decrease level of glucose in blood
61
Explain the mechanism of tyrosine phosphatase.
1. Ligand binds to receptor causes a change that activates enzyme tyrosine phosphatase 2.Target proteins dephosphorylated by tyrosine phosphatase activity 3. Causes regulation of downstream cell-signalling events Response- maturation of lymphocytes
62
Why is receptor tyrosine phosphatase different to the other enzyme linked receptors?
Only 1 transmembrane domain and dephosphorylates target.
63
Which receptor requires a ternary complex to be formed to activate the catalytic activity of the enzyme?
Receptor Serine-Threonine Kinase
64
Which receptor is the insulin receptor an example of?
Receptor Tyrosine Kinase
65
What are the differences between cell surface receptors and intracellular (nuclear) receptors?
Cell surface- Cannot cross membrane, located outside of cell, for hydrophilic signalling molecules activate wide variety of intracellular "signal transduction" pathways, including gene regulation Intracellular- Signalling molecule- Cross plasma membrane, Inside cell, Hydrophobic signalling molecules act as transcription molecules in nucleus to regulate gene transcription
66
What are hormones classed as? What are the two types?
First messengers Lipophilic or hydrophilic
67
Explain the structure and mech of action of lipophilic hormones?
-Lipid soluble- chemically derived from cholesterol -Relatively small- pass through plasma membrane -Enter target cells- bind to intracellular receptor- activate genes produce new proteins -Slower acting that hydrophilic hormones
68
Explain structure and mech of action of hydrophilic hormones.
-Water soluble- derived from amino acids -Binds to receptors on target cell membranes- activates signal transduction- produces second messenger -Activate existing enzymes- small amount result in significant cellular change -Faster action than lipophilic hormones
69
Explain the simple pathway of a hormone activating a nuclear receptor.
Lipophilic hormone enters cell and activates a nuclear receptor Activates genes Synthesise new proteins or enzymes Cell responds
70
What are some example ligands for intracellular-nuclear receptors?
Steroid hormones e.g Androgens, Estrogens and progesterone Corticosteroids(adrenal gland) Glucocorticoids (adrenal- stimulate glucose production) Mineralocorticoids (adrenal- kidney balance water and regulate salt) Other- Thyroid, Vitamin D3, Retinoic acid
71
What are the two types of intracellular receptors? which ones are which
Cytoplasmic and nuclear Cytoplasmic- GR, MR Nuclear- ER, PR,TR,RAR
72
Explain the structure of a nuclear receptors and the different domains.
A/B & E- transactivation domain (ligand binding domain- causes change to DNA to initiate transcription) C- DNA-binding/dimerization (Allow dimerization of receptors and binding to DNA) D- Nuclear localization domain (Allow receptor to enter the nucleus to maintain nuclear localization)
73
Which domain of a nuclear receptor allows initiation of transcription?
Transactivation domain
74
Explain the mechanism of an intracellular cytoplasmic receptor activation.
1. Receptor located in cytoplasm 2. Ligand enters cell and causes receptor activation 3. Ligand binds which dislodges regulatory/repressor protein(which is bound to the receptor) 4-Ligand-receptor complex enters nucleus and binds to specific DNA sequence (in promoter region) 5.Gene transcribed and translated to produce protein. Or gene expression is inhibited.
75
Explain mechanism of nuclear receptor activation.
1. Lipid-soluble hormones diffuse through plasma membrane and bind to nuclear receptor 2. Hormone-receptor complex binds to hormone response element of DNA, acting as transcription factor. 3. Binding of hormone receptor complex to DNA stimulates synthesis of mRNA 4. mRNA leaves nucleus passes into cytoplasm and binds to ribosomes, directs synthesis of specific proteins 5. Newly synthesised proteins stimulate cell response to lipid-soluble hormones
76
Which receptor takes longer to produce a response, a cytoplasmic or nuclear?
Nuclear- ligand has further distance to travel
77
How does the transcription-activating domain activate gene expression?
Steroid hormone binds to intracellular receptor Inhibitor is released to expose DNA binding site on receptor Receptor binds to DNA and activates gene expression
78
What is an example of a steroid signalling hormone and what is its function? Which channel does it activate?
Aldosterone- stimulates Na+ retention if dietary Na+ is reduced Epithelial Na+ channel (ENAC)- in collecting duct- kidney
79
Why is the expression of in ENAC channels low in normal people?
Express a protein called Nedd4-2 which binds to ENAC causing the channel to be internalised which limits the rate of Na recovery so Na+ can be lost in the urine
80
How does the release of aldosterone lead to the retention of Na+?
Aldosterone enters cell- crosses cell membrane then binds to the cytoplasmic receptor, enters nucleus, binds to DNA, promote gene expression. (general mechanism) This induces expression of a protein kinase that sensitizes SGK1. This then phosphorylates protein Nedd4-2 which can then leave the cell and prevent proteins binding to ENAC ENAC remains in membrane and results in increased Na+ retention.

Pharmacology (4 decks)

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