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BB10005 COPY > Cell membranes > Flashcards

Cell membranes Flashcards

1
Q

What is the primary functions of a membrane?

A
  1. Membranes are barriers/ define boundaries
  2. Receive information- receptors on cell surfaces
  3. Important and export of molecules
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2
Q

What are the barrier functions of membranes?

A
  1. Preventing the loss of required metabolites
  2. protecting against unwanted outside molecules
  3. storing electrical chemical energy and energy production
  4. electrical signalling.
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3
Q

What are some of the functions of proteins in membranes?

A
  1. Selective permeability
  2. maintaining ionic composition on either side
  3. maintaining cytoplasmic pH- 7.2-7.4
  4. controlling cytoplasmic osmotic pressure
  5. sensing the environment
  6. anchoring cytoskeletal structures
  7. mediating cell/cell and cell extracellular matrix interactions
  8. carrying out membrane requiring enzymatic reaction.s
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4
Q

What are aquaporins?

A
  1. Specialised channels for water to flow through the cell membrane.
  2. Help control cytoplasmic osmotic pressure
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5
Q

What percentage of total membranes does the plasma membrane make up in a cell?

A

2%.

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6
Q

Lipids are amphipathic. What does this mean?

A

They have a hydrophobic portion and a hydrophilic portion.

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7
Q

What is the energetically favoured structure of phospholipid bilayers?

A
  1. To form sealed compartments (liposome) rather than a planar bilayer as there are no hydrophobic edges in contact with water.
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8
Q

What are glycerophospholipids?

A
  1. They are based on 3 carbon glycerol
  2. 2-carbon ester linked to fatty acid
  3. One linked to phosphate
  4. Ester linkages but sometimes different
  5. Diversity as X group different- thing attached to phosphate-gives different names
  6. Head groups have different properties
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9
Q

What is the phophatidyl group?

A

Phospholipids that incoorporate choline as a head group.

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10
Q

What other types of molecules are found in membranes?

A
  1. Glycolipids- sphingolipids
  2. Sterols- cholesterol
  3. Phospholipids- glycerophospholipids, sphingolipids
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11
Q

What does it mean that lipid bilayers are fluid?

A
  1. Rotate freely
  2. Flip flop-
  3. It is not energetically favorable for a polar head group to ‘flip’ from one leaflet to the other as this requires a polar molecule moving through a hydrophobic environment.
  4. not energetically favourable so probably need proteins
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12
Q

Why is membrane fluidity important?

A
  1. It provides the compromise between rigid, ordered structure and completely fluid non-viscous liquid
  2. It allows for interactions to take place in the membrane. e.g makes it possible for groups of membrane proteins to assemble at particular sites within the membrane.
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13
Q

What was an early experiment that showed membrane fluidity?

A
  1. Two cells labelled different were fused together artifically.
  2. Originally the different labellings remained separate however they ended up being mixed together.
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14
Q

What factors affect membrane fluidity?

A
  1. Temperature
  2. cholesterol
  3. saturation of acyl chains
  4. length of acyl chains.
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15
Q

How can a c=c double bond influence membrane fluidity?

A
  1. It produces a kink in the acyl chain which leads to packing defects.
  2. van de Waals interactions- solid interactions between lipids in membrane if saturated
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16
Q

What is cholesterols effect on fluidity of the membrane?

A
  1. It decreases the bilayer fluidity

2. improve the packing properties.

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17
Q

What is lipid asymmetry?

A
  1. The idea that the two bilayers of the membrane are asymmetrical and have different compositions.
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18
Q

What are the two halves of the lipid bilayer called?

A
  1. The two leaflets.
  2. Cytoplasmic leaflet- faces cytoplasm- negatively charged lipids usually only found here e.g. phosphatidylcholine
  3. Extracellular leaflet- glycolipids only found here
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19
Q

Why are there so many different lipids?

A
  1. They have important effects of biological properties, fluidity, curvature and fusion properties.
  2. They can act as signalling molecules,
  3. Take part in cell interactions
  4. Can effect the activity of membrane proteins.
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20
Q

What molecules can and cannot pass through lipid bilayers?

A
  1. Small hydrophobic molecules pass through
  2. Small uncharged, polar molecules can pass through, 3. larger uncharged polar molecules cannot
  3. ions also cannot pass through the membrane.
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21
Q

What different types of membrane proteins are there?

A
  1. Integral membrane proteins
  2. peripheral membrane proteins
  3. lipid anchored membrane proteins.
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22
Q

What are the differences between the types of membrane proteins?

A
  1. a) Integral span the entire bilayer and have domains of protein which are on both sides of the membrane
    b) Portions which are cytoplasmic and others which are non cytoplasmic
  2. a) peripheral lie on the outer surface
    b) Can be removed with high salt wash, lipid associated
    c) Interact with head groups of lipids via non-covalent interactions
    d) Protein associated- interact with integral membrane proteins
  3. a) lipid anchored are attached via a lipid molecule.
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23
Q

What are the four different types of R group?

A
  1. Nonpolar aliphatic R groups
  2. Aromatic R groups
  3. Polar uncharged R groups
  4. Charged R groups.
  5. Learn which are which
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24
Q

What R groups are most suited to the hydrophobic environment of the lipid bilayer?

A

Nonpolar side chains are most suited.

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25
Q

Which amino acids contain nonpolar aliphatic R groups?

A

Glycine, alanine, valine, leucine, methionine and isoleucine.

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26
Q

What joins amino acids together?

A

Peptide bonds.

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27
Q

What is released when two amino acids are joined together?

A

A water molecule.

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28
Q

How is the problem of the polar peptide bonds not being energetically favoured in the hydrophobic core overcome?

A
  1. The polar nature of peptide bonds is not energetically favourable in the hydrophobic core of the lipid bilayer.
  2. So hide R groups
  3. Hydrogen bonding between the partial negative charge in the carbonyl oxygen and the partial positive charge of the amide hydrogen in a regular pattern neutralises the negative charge.
  4. Side chains of amino acids contacting the hydrophobic core of the bilayer are preferentially non-polar
  5. The peptide backbone should be hydrogen bonded (in some secondary structure) to prevent unfavourable interactions with the lipid bilayer
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29
Q

What groups are involved in the formation of a peptide bond?

A

The amino group of one amino acid and the carboxyl group of another.

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30
Q

What is another secondary structure with a regular pattern of hydrogen bonding?

A

The formation of a beta sheet- minority of membrane proteins

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31
Q

What is the average total width of the lipid bilayer?

A
  1. 50 angstroms= 5nm
  2. Head group 10 A each
  3. Tails altogether 30 A
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32
Q

How many amino acids are required to span the bilayer in an alpha helical conformation?

A
  1. One residue= 1.5 A
  2. To span hydrophobic core of membrane (30 Å)
  3. Need ~20 residues
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33
Q

How many amino acids are required to span the bilayer in an extended conformation?

A
  1. One residue= 3.5 A
  2. To span hydrophobic core of membrane (30 Å)
  3. Need ~ 8-9 residues.
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34
Q

How can membrane protein structure be predicted from the sequence?

A

Hydrophobicity analysis.

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35
Q

Give examples of some of the hydrophobicity scales?

A
  1. Kyte
  2. Doolittle
  3. Engelmann
  4. Steitz.
36
Q

What are some of the functions of membrane proteins?

A

Transporters, linkers, receptors and enzymes.

37
Q

What is the difference between carrier proteins and ion channels?

A
  1. Carrier proteins allow solutes to cross by passive or active transport
  2. Ion channels are selective and gated and have a continuous ‘channel’ through the membrane through which ions can travel.
38
Q

What happens when substrates bind to membrane proteins?

A

There is a conformational change that results in the substrate being released on the other side of the membrane.

39
Q

What are the three types of transport across the membrane?

A
  1. Uniport- Single molecules type
  2. symport
  3. antiport.
40
Q

What is coupled transport?

A

The transport of 2 different types of molecules that are interdependent on one another for transport.

41
Q

What is symport?

A

Transport of two different molecules in the same direction.

42
Q

What is antiport?

A

The transport of two different molecules in the opposite direction.

43
Q

Give an example of a passive facilitative transporter and how it works

A
  1. GLUT1, a glucose transporter.
  2. Molecules moves across the membrane without the expenditure of energy by the transport protein
  3. Down concentration gradient
  4. High concentration outside cell- increases likeliness of binding
  5. Conformational change
44
Q

What is an example of a symporter and how does it work?

A
  1. Lactose permease
  2. Transport lactose from low concentration to high concentration inside cell
  3. Co-transporting proton
  4. E.coli- actively pumps protons to outside cell
  5. Lactose and protons- cause conformational change
  6. Proton leaves as low concentration inside cell
  7. Lactose can’t bind now as no proton- so is released inside cell despite higher concentration
  8. Requires energy to pump protons outside cell- secondary active transport
45
Q

What is membrane potential?

A

The charge difference between the two sides of the membrane.

46
Q

What makes up an electrochemical gradient?

A

The concentration gradient and the membrane potential.

47
Q

What are examples of active transport?

A

The glucose sodium symporter and the Na/K ATPase antiport.

48
Q

please do the extra reading lol

A

transporter thing

49
Q

What is Nexium?

A
  1. One of the biggest selling prescription drugs that is effective against heartburn and stomach ulcers
  2. It inhibits the stomachs H+/K+ ATPase.
50
Q

What is patch clamp recording?

A
  1. One way of measuring ion channels is by a method called patch clamp
  2. A small area of membrane (hopefully containing channel proteins is removed from a membrane and seals the end of a glass capillary.
  3. Patch clamp recording can be used to measure ion channel activity.
  4. A small area of membrane seals the end of a capillary.
  5. Current only flows when ion channels are open.
51
Q

How does patch clamp recording work?

A

Current can only flow through when the ion channels are open, which can be used to measure ion channel activity.

52
Q

What is gating?

A

When the opening and closing of ion channels is dependent on a stimulus.

  1. Voltage gated, respond to voltage differences across membranes
  2. Ligand gated, the acetylcholine receptor
  3. Mechanically gated in auditory cells
53
Q

What is the mechanism for signalling in neurones?

A
  1. The form of the signal carried by neurons is always the same. Changing electrical potential across the plasma membrane
  2. Ion channels are responsible for this signalling
  3. A stimulus that causes sufficient depolarisation of the plasma membrane causes voltage gated Na+ channels to open
  4. Na+ enters the cell depolarises the membrane further causing more Na+ channels to open. This is self perpetuating
  5. Channels then become inactivated or else the membrane would permanently be depolarised
54
Q

How does the propagation of action potentials only occur in one direction?

A
  1. Action potential influences neighbouring regions of plasma membrane and therefore there is a wave of depolarisation.
  2. The action potential only moves in one direction as behind it channels have been inactivated.
  3. Membrane patches that have been depolarised return to their resting state
  4. The ion channels in front (to the right) of the wave of depolarisation ‘sense’ the local change in membrane potential and open.
  5. Those ion channels behind are inactivated, so cannot re-open until the membrane has re-polarised and another stimulus that causes the membrane to de-polarise once more to/or beyond threshold potential is received.
55
Q

What happens at nerve terminals?

A
  1. When the action potential reaches nerve terminal voltage gated Ca2+ channels open
  2. Ca2+ enters the cell
  3. This causes fusion of vesicles with the plasma membrane and the release of neurotransmitters
56
Q

What is an example of an inherited disease caused by defects in ion channels and what is the result of this disease?

A
  1. Cystic fibrosis caused by defects in a chloride channel
  2. Leads to lung congestion and infections
  3. Unclear why a defect in the channel leads to disease
57
Q

What are three types of cell surface receptors?

A
  1. Ion channel linked
  2. G-protein linked
  3. enzyme linked.
58
Q

What are G protein coupled receptors?

A
  1. They are 7 transmembrane spanning receptors that have a huge potential as drug targets.
  2. They have a G protein attached to them that can cause downstream effects when the receptor is activated.
  3. The binding of the ligand causes conformational changes.
  4. C-elegans (worm) genome appears to have >1000 GPCR genes (5% of genome)
  5. Estimates are that we (humans) have approx. 800 GPCRs
  6. Huge potential as drug targets
  7. More than a quarter of all prescription drugs bind to GPCRs
59
Q

What is an example of an enzyme receptor?

A
  1. Insulin receptor
  2. Enzyme linked receptors are receptors that have enzymatic activity altered (often stimulated), upon binding of a ligand.
  3. The insulin receptor, upon insulin binding, becomes active and can add phosphate molecules to tyrosine residues in proteins.
  4. The insulin receptor is thus classed as a tyrosine kinase.
  5. A kinase adds phosphate groups, a phosphatase removes phosphate groups.
60
Q

What amino acids contain aromatic R groups?

A

Phenylalanine, tyrosine, tryptophan.

61
Q

What amino acids contain polar, uncharged R groups?

A

Serine, threonine, cysteine, proline, asparagine and glutamine.

62
Q

What amino acids contain charged R groups?

A

Lysine, arginine, histidine, aspartate and glutamate.

63
Q

How is an antiparallel beta sheet formed?

A

Adjacent beta strands run in opposite directions - every other side chain extends above or below the sheet.

64
Q

What length of the lipid bilayer is made up of the hydrophobic tails?

A

30 angstroms.

65
Q

What is the total width of the lipid bilayer?

A

50 angstroms.

66
Q

In an extended conformation what is the length of one residue?

A

3.5 angstroms.

67
Q

Describe the structure of alpha helix?

A
  1. Peptide bond 1 H-bonded to peptide bond 4, 2 to 5 – 3 peptide bonds away
  2. 3.6 residues per turn (5.4 Å) = 1.5 Å/residue
  3. In a fully extended conformation 3.5 Å /residue
  4. Side chains point out from helix
  5. Majority
68
Q

What are porins?

A

Beta barrel membrane proteins that cross a cell membrane and act as a pore through which molecules can diffuse.

69
Q

What are carrier proteins needed for and describe their structure

A
  1. To transport nearly all small organic molecules, such as nucleotides, sugars and amino acids.
  2. Carrier proteins are thought to have specific solute binding sites (ie glucose binding site)
  3. Switch between different conformations which are open to the two sides of the membrane (Alternative access model).
  4. There is no continuous channel through the membrane.
70
Q

What is another example of a symporter?

A

The glucose-sodium symporter.

71
Q

What is required for symporters to work?

A

An ion gradient that is generated by active transport.

72
Q

What type of electrochemical gradient will result in the most movement across the membrane?

A
  1. A very large concentration gradient and a very large membrane potential
  2. very positive on the outside and negative on the inside.
73
Q

What is secondary active transport?

A
  1. The idea that the membrane potential in the symporter has to be generated using active transport.
74
Q

What other sources of energy can be used to drive pumps?

A

Light energy - bacteriorhodopsin uses light energy to pump protons across a membrane.

75
Q

What is the difference between a kinase and a phosphatase?

A

A kinase adds phosphate groups whereas a phosphatase removes phosphate groups.

76
Q

What is an example of a membrane protein that has another function not previously mentioned?

A
  1. Linkers
  2. Cell-Cell contacts
  3. Cell-extracellular matrix adhesion (Integrins)
77
Q

Why are intracellular membranes needed? Give an example?

A
  1. Lysosome-
  2. degrade proteins and sugars so needs to be kept separate
  3. Acid hydrolases- enzymes which degrade macromolecules
  4. Work at Ph- 5
78
Q

What happens if a membrane is punctured

A
  1. Natural to reseal so hydrophobic parts not exposed to aqueous environment
79
Q

What is a sphingolipid

A
  1. Long chain of carbons- sphingosine
  2. Fatty acid linked by amino linkage to sphingosine
  3. Can have different head groups attached
  4. If Phosphate – phospholipids
  5. If Sugar- glycolipids
80
Q

How does temperature affect the fluidity of the membrane

A
  1. Not such a problem for humans as thermoregulation
  2. E. coli- change structure of lipids as can’t control temperature
  3. At high temp- grow lipids that are saturated
  4. Low temp- unsaturated
81
Q

What percentage of protein coding genes encode membrane proteins

A
  1. 20-30% of all ORFs (protein coding genes) in genomes are predicted to encode membrane proteins
  2. Larger genomes contain a larger fraction than smaller ones
  3. The structures of around 300 membrane proteins are known at high resolution.
82
Q

Describe how to predict membrane structure using hydrophobicity

A
  1. Each individual amino acid has a hydrophobicity value
  2. Integral membrane proteins may span the membrane many times
  3. Use an average over a number of amino acids (usually 15-20)
  4. Average hydrophobicity of a stretch of amino acids (15-20) is calculated
  5. It is plotted against the position of the window (stretch is shifted by one amino acid for each position)
  6. Troughs- show transmembrane regions- as show hydrophobicity
83
Q

Describe the glucose sodium symporter

A
  1. This requires a sodium gradient across the membrane (ie high sodium outside the cell) in order to co-transport glucose against it’s concentration gradient.
  2. This is sometimes called secondary active transport as the sodium gradient (although a form of stored energy) has to be generated by active transport (ie by the Na/K ATPase)
84
Q

Describe the Na/K ATPase transporter

A
  1. Na/K ATPase is an antiporter.
  2. It transports (pumps) 3 Na ions out of the cell and 2 K ions into the cell for each ATP that is hydrolysed.
  3. ATP is the fuel/energy source for the pump.
  4. The pumping of Na ions out of the cell generates a Na gradient across the membrane.
85
Q

What is the resting potential and threshold potential and what happens at each

A
  1. When the membrane is at resting potential (-60 mV) a voltage gated ion channel is closed.
  2. Upon depolarisation to threshold potential (-40 mV) the ion channel opens (this depolarises the membrane further (+40 mV) and influences neighbouring ion channels).

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