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Membranes Flashcards

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1
Q

What are the general functions of biological membranes?

A 
Selective permeability
Communication
Recognition of signalling molecules
Signal generation in response to stimuli
Endocytosis
Excytosis
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2
Q

What are the 4 permitted motions of the phospholipid bilayer?

A

Flexion
Rotation
Lateral diffusion
Flip-flop

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3
Q

What are the effects of cholesterol in the phospholipid bilayer?

A

Rigid steroid ring restricts motion of fatty acid chain reducing fluidity at high temperatures
Flexible tail reduce phospholipid packing increasing fluidity at low temperatures

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4
Q

What 2 structures are formed when an amphipathic molecule is put into water?

A

Lipid micelle

Lipid bilayer

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5
Q

What are the functional importance of proteins in membranes?

A

Facilitate diffusion via pumps and transporters
Create ion gradients via ion channels
Affect the specificity of cell responses
Transduce energy

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6
Q

What 3 modes of motion are proteins permitted to do in the bilayer?

A

Rotation
Lateral diffusion
Conformational change

NOT FLIP FLOP

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7
Q

How can proteins in the peripheral membrane be removed?

A

Changes in pH (change their hydrogen bond interactions)

Changes in ionic strength (change their electrostatic interactions)

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8
Q

How can proteins in the integral membrane be removed?

A

Using detergents

Using organic solvents

(Both compete for non-polar interactions)

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9
Q

Where do proteins destined for the cytosol or mitochondria get translated?

A

Free polyribosomes

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10
Q

Where do proteins that are to be secreted via exocytosis translated?

A

Rough ER

Modified and packaged in the Golgi

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11
Q

What are the components of the erythrocyte cytoskeleton?

A 
Band 3
Ankyrin (band 4.9)
Spectrin
Glycophorin A
Band 4.1
Adducin 
Actin
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12
Q

What is the general structure of cholesterol?

A

Polar head group

Rigid steroid ring structure

Non-polar hydrocarbon tail

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13
Q

What does mutation in spectrin cause and what are the resulting diseases?

A

Causes loss of flexibility in red blood cells

Haemolytic anaemias

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14
Q

What are the 2 types of haemolytic anaemias? Describe their pathology.

A

Hereditary spherocytosis - spectrin is depleted by 40-50% due to loss of 1 spectrin allele

Hereditary elliptocytosis - spectrin cannot assemble properly due to defect in spectrin molecule

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15
Q

What is the pathology of duchenne muscular dystrophy?

A

Loss of dystrophin leading to loss of membrane stability so that when the muscle contracts, the membrane falls apart

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16
Q

Which molecules are permeable and impermeable to the lipid bilayer?

A

Permeable - hydrophobic molecules and small, uncharged polar molecules

Impermeable - large uncharged molecules and ions

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17
Q

What are the 3 main fluid compartments in the body, giving an example of each?

A

Intracellular fluidity - cytoplasm

Extracellular interstitial fluid - cerebrospinal fluid, synovial fluid

Intravascular - blood plasma, lymph

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18
Q

Define hypervolemia

A

Excess extracellular fluid causing overhydration

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19
Q

Define isotonic and the other 2 extremities

A

Isotonic - levels of sodium in and out of the cell are equal to osmotic pressure levels

Hypotonic - sodium levels in the cell are low causing inflow of sodium resulting in cell swelling and oedema
Hypertonic - sodium levels in the cell are high causing outflow of sodium resulting in cell shrinkage

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20
Q

Regarding the following ions, which ones are more abundant intracellularly and extracellularly - sodium, chlorine, potassium and calcium

A

Sodium - more extracellularly
Chlorine - more extracellularly
Potassium - more intracellularly
Calcium - more extracellularly

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21
Q

What are the 3 types of transporters?

A

Uniport - moves 1 ion/molecule into the cell
Symport - moves 2 ions/molecules in the same direction
Antiport - moves 2 ions/molecules in different directions

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22
Q

What are some differences between active and passive transport in the cell?

A

Passive - depends on the electrochemical and concentration gradient, energy released exothermically, examples include simple and facilitated diffusion

Active - moves against electrochemical and concentration gradient, uses ATP as fuel, ATPases are good examples

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23
Q

What sets the resting membrane potential of the cell?

A

The passive flow of potassium out of the cell

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24
Q

Regarding cellular activity, describe the pathology of cholera.

A

The cholera toxin (CTx) enters the cell through receptor mediated endocytosis - adds an ADP-ribose to alpha subunit of Gs protein - prevents deactivation of the protein - feeds into the increased activity of protein kinase A - an enzyme that increases the activity of the CFTR transport channel leading to more amounts of chlorine leaving the cells causing more water to leave the cell also which results in diarrhoea and dehydration

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25
What is the mechanism of the sodium pump?
An antiport that uses active transport 3 sodium molecules out, 2 potassium molecules in Drive secondary active transport which controls pH inside cell, regulates cell volume, absorbs sodium in epithelia and takes up nutrients
26
Why is high intracellular calcium toxic to cells?
High intracellular calcium activated enzymatic pathways which can break down the cell membrane, DNA, ATP and other proteins causing irreversible cell damage
27
Describe the mechanism of the sodium calcium exchanger (NCX)
A sodium and calcium antiport that acts as a secondary active transport 1 calcium ion out, 3 sodium ions in Removes most intracellular calcium
28
On a cellular basis, what can happen when there is lack of oxygen?
ATP can’t be produced because oxidative phosphorylation needs oxygen - lack of ATP results in lack of active transport - sodium pump are unable to function - results in higher of concentration of intracellular sodium - NCX transporter switches directions to compensate for increased intracellular sodium - leads to increase in intracellular calcium which is toxic to cells
29
Describe the mechanism of the plasma membrane calcium ATPase (PMCA)
A calcium uniport that uses active transport to move calcium out of the cell
30
Describe the mechanism of SERCA
Sarcoplasmic reticulum calcium ATPase - a calcium and hydrogen antiport that uses active transport, for every calcium that enters the cell, 1 hydrogen molecule is released
31
How do cells control their cellular pH?
Use of buffers and acid and base extruders
32
What is the mechanism of an acid extruder and give an example of one
They make the cell less acidic by moving hydrogen out of the cell Examples: sodium hydrogen exchanger (NHE) and sodium bicarbonate cotransporter
33
What is the mechanism of a base extruder and give an example of one
Makes the cell more acidic by moving bicarbonate out of the cell Example: anion exchanger - band 3 aka chlorine bicarbonate exchanger
34
How much water is in the average human and how is it shared?
~40 - 42 litres ~ 28L is in the intracellular compartment ~ 14L is in the extracellular compartment
35
What are the types of resuscitation fluids that can be used in a clinical context?
``` Colloids Crystalloids Physiological fluids Glucose solution Mixture of fluids Blood ```
36
What is a resting membrane potential?
The electric potential of the cell that exists as a result of ions moving into and out of the cell membrane
37
What type of cells have the largest resting potentials and why? What are the value of the potentials?
Cardiac and skeletal muscle cells have the largest membrane resting potentials of ~ 80-90 mV because they have chloride channels which causes chlorine to leak into the cell
38
What is the resting membrane potential of nerve cells?
~ 50 - 75 mV
39
What is the definition of an ion channel?
A protein that enables specific ions to cross cell membranes
40
Influx of which ions cause depolarisation?
Sodium and calcium
41
Influx of which ions cause hyperpolarisation?
Potassium and chlorine
42
What are the 3 types of gated channels?
Ligand, voltage and mechanical
43
What are the 4 types of synaptic transmission?
Nerve cell - nerve cell Nerve cell - muscle cell Nerve cell - gland cell Sensory cell - nerve cell
44
What are some examples of specialised membranes?
``` Placenta Kidney tubules Intestinal villi Meninges of the brain Mitochondria ```
45
What is neonatal abstinence syndrome?
When a baby suffers from withdrawal symptoms after birth due to exposure to illicit or prescription drugs via placental transfer
46
What is an action potential?
A change in cell membrane potential that is initiated by a stimulus causing a threshold level to be reached
47
What influences the magnitude of the action potential?
Concentration of sodium in extracellular fluid
48
What is the difference between absolute and relative refractory period?
Absolute - period following an action potential when it is impossible to stimulate another action potential Relative - period immediately following an action potential when it is possible but difficult to stimulate another action potential
49
What are the 3 states of ion channels?
Open Closed Inactivated
50
What is a graded potential?
Change in membrane potential that varies in size instead of being an all or nothing response
51
How do local anaesthetics work?
Bind temporarily to voltage-gated sodium channels to prevent generation and conduction of action potentials
52
What 2 factors affect the propagation of action potentials in nerve cells?
Diameter of the axon | Myelination
53
Describe the sequence of actions once an action potential has been reached
Action potential reached - sodium voltage gated channels are opened in the axon hillock - depolarisation occurs - sodium spreads further down the axon initiating action potential along the axon - potassium channels open in axon hillock - repolarisation - sodium ions are unable to trigger another action potential in area of axon (absolute refractory period) - occurs further down the cell too (signal propagation)
54
What is the pathology of multiple sclerosis?
An autoimmune disease that leads to breakdown/damage of myelin sheath surrounding the nerves in the CNS resulting in decreased conduction velocity
55
What are the 2 types of synapses? Describe them
Chemical | Electrical
56
What are the differences between the muscarinic and nicotinic receptors?
Muscarinic - metabotropic receptors that use g-proteins Nicotinic - ligand gated ionotropic receptors that depolarise the cell by allowing positively charged ions to enter
57
Where can electrical synapses be found?
``` Cardiac muscle Purkinje fibres Brain stem Retina Bladder Uterus ```
58
What is the pathology of myasthenia gravis?
An autoimmune disease caused by antibodies that target nicotinic acetylcholine receptors on post synaptic membranes of skeletal muscle leading to their loss of function, resulting in patients suffering from profound muscle weakness and fatigue
59
What is a ligand?
Any molecule that binds specifically to a receptor site, resulting in activation of the receptor
60
What is the structure of nicotinic acetylcholine receptors?
Different subunits each with 4 transmembrane domains
61
What are clathrin coated pits?
Regions of the cell membrane specialised in receptor-mediated endocytosis
62
What are G proteins?
A family of proteins that bind with guanine nucleotides to transducer energy produced by agonists binding to and activating receptors
63
What is the basic structure of a g-protein coupled receptor?
Single polypeptide chain 7-transmembrane spanning regions Extracellular N terminal Intracellular C terminal
64
Give some examples of some g-protein coupled receptors?
Beta-adrenoceptors Dopamine receptors Histamine receptors
65
How do G proteins bind to g-protein coupled receptors and what happens post binding?
Once a ligand/molecule binds to 1 of the 2 binding sites on the GPCRs, the C terminal region inside the cell will couple with the g-protein resulting in a conformational change in the C terminal
66
Describe the process of a ligand/agonist binding to a GPCR
Ligand/agonist binds to 1 of the 2 binding domains of the GPCR - GDP phosphorylates and becomes GTP - GTP binds to the alpha subunit of the GPCR - alpha subunit separates from the beta and gamma subunit taking the GTP with it - the alpha subunit and beta-gamma subunit can then go ahead to interact with effector proteins independently
67
Describe the physiology of morphine
A string painkiller that works to reduce calcium influx into pre-synaptic membranes in the CNS and PNS by inhibiting voltage-operated calcium channels (VOCC) which results in reduction of neurotransmitter release therefore reducing pain
68
In respect to affinity and efficacy, describe agonists and antagonists
Agonists have affinity and intrinsic efficacy Antagonists have affinity but no efficacy
69
What is Kd and what do the values mean?
Kd - a measure of a receptor’s affinity High Kd means low affinity Low Kd means high affinity Kd is also the concentration of the ligand required to occupy 50% of the available receptors
70
What is EC50?
The effective concentration of a receptor that will give 50% of the maximum response
71
What 3 things are needed for drugs to work at maximum effect?
Affinity to the receptor Intrinsic efficacy Specificity to work on the right receptor
72
What is a partial agonist? What are they used for?
Agonists that have affinity but only partial efficacy at the receptor Used for pain relief and recreational use
73
What happens to receptor numbers at low activity and high activity?
At low activity, they increase in number to increase activity At high activity, they decrease in number to decrease activity
74
What is a spare receptor?
Receptors can be classified as spare when the maximum response can be achieved without occupying all the receptors
75
What is the efficacy of a drug?
A measure of how good a drug is at producing a specific response
76
What 3 mechanisms do antagonists use? Describe them
Reversible competitive antagonism - reversible binding of an antagonist to the orthosteric site of a receptor Irreversible competitive antagonism - irreversible binding of the antagonist to the orthosteric site of a receptor (irreversible bc the antagonist dissociates slowly or not at all) Non-competitive antagonism - antagonist binds to the allosteric site of the receptor
77
What is IC50?
The inhibitory concentration of an antagonist which gives you 50% inhibition of the receptor
78
What is naloxone?
A high affinity competitive antagonist that can be used to treat drug overdoses like heroin
79
What is the oral bioavailability of a drug?
Proportion of a drug given orally that reaches circulation unchanged
80
What are the 2 classes of drugs and what do they mean?
Class 1 - drugs that can be used at a lower dose than the number of albumin binding sites Class 2 - drugs that have to be used at a greater dose than the number of binding sites
81
Where do drug metabolism and e creation predominantly occur?
Metabolism - predominantly in the liver, can also be in the kidneys, lungs and blood Excretion - renal excretion
82
What is 1st order and zero order kinetics of drugs? Give some examples of drugs that following the types of kinetics
1st order - rate of drug elimination increases as drug concentration increases (most drugs use this type) Zero order - rate of drug elimination is a constant amount (e.g. heparin, warfarin and aspirin)
83
How is epinephrine made?
Phenylalanine hydroxylated to tyrosine - tyrosine is hydroxylated to DOPA - DOPA is decarboxylated to dopamine - dopamine is made into norepinephrine - norepinephrine transferased to epinephrine
84
By what 2 mechanisms can noradrenaline be removed?
Termination - re-uptake into the presynaptic terminal by a sodium dependent, high affinity transporter Metabolism - in presynaptic terminal, noradrenaline that has not been taken up into vesicles can be metabolised by 2 enzymes: monoamine oxidase and COMT
85
Give an example of a drug that acts on adrenergic nerve terminal
Alpha-methyl-tyrosine Alpha-methyl-DOPA CarbiDOPA
86
What are opioids and what are they used for?
Proteins that act on opioid receptors in the brain and spinal cord leading to increased potassium leaving the cell causing hyperpolarization resulting in reduced pain
87
What can repeated exposure to drugs cause?
``` Desensitisation Tachyphylaxis Resistance Dependence Tolerance ```
88
What is the BNF?
British National Formulary - contains a comprehensive list of all drugs licensed in the U.K.

Membranes (1 decks)

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