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YEAR 1 - Physiology and Pharmacology (Anton) > 1. Cellular and Molecular Structure and Function > Flashcards

1. Cellular and Molecular Structure and Function Flashcards

1
Q

Give 4 reasons why membranes are important.

A

1) Form cells by separating cytoplasm from external medium
2) Act as a permeability membrane to maintain ionic gradients
3) Form internal organelles
4) Enable integration of cell-surface receptor proteins

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2
Q

Give some examples of places where membranes are found.

A
  • Plasma membrane
  • ER
  • Golgi apparatus
  • Mitochondria
  • Nuclear envelope
  • Lysosomes
  • Secretory vesicles
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3
Q

Describe how the composition of a cell membrane may be analysed and why.

A
  • RBCs can be used for a pure fraction of a membrane
  • This is because RBCs have few organelles, which may have different membrane compositions
  • So RBCs provide a pure membrane fraction
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4
Q

Why are RBCs ideal for studying cell membranes?

A
  • Large number of cells can be obtained easily
  • Anucleate and lack intracellular organelles
  • Easy to manipulate (so can study both inside and outside of membrane)
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5
Q

Describe how a RBC can be manipulated for membrane study.

A
  • Placed in hypotonic solution to lyse
  • Washed and resealed either right-side-out or inside-out vesicles
  • Outside can now be studied
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6
Q

Describe the general structure of a membrane.

A

Fluid mosaic model where proteins are floating freely in a sea of phospholipid.

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7
Q

Describe the structure of a phospholipid.

A
  • 2 fatty acids
  • Glycerol
  • Phosphate
  • Alcohol (e.g. choline, serine, ethanolamine, etc.)

2 fatty acids attach to glycerol at the tail, while phosphate and alochol form a chain and attach to the glycerol at the top

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8
Q

Draw the structure of a phospholipid.

A
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9
Q

What is the difference between different phospholipids?

A

The variable species at the top of the phosphate head (e.g. choline, serine, ethanolamine). It is an alcohol.

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10
Q

Which part of a phospholipid is hydrophilic and which part is hydrophobic?

A
  • Hydrophilic - Phosphate head
  • Hydrophobic - Fatty acid tail
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11
Q

How many double bonds are there in the fatty acids in a phospholipid?

A

Only one, on one of the fatty acids.

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12
Q

What does the double bond in one fatty acid tail of a phospholipid cause?

A
  • Causes bend in the chain
  • So the phopshlipids can’t pack as tightly
  • So membrane fluidity is increased
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13
Q

What are the principle phospholipids?

A
  • Phospatidylcholine (lecithin)
  • Phosphatidylserine
  • Phosphatidylethanolamine
  • Sphingomyelin
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14
Q

In terms of hydrophobicity/hydrophility, what type of molecule is a phospholipid?

A

Amphipathic - it has both hydrophobic and hydrophilic parts.

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15
Q

Why does a C=C bond in a fatty acid tail in a phospholipid induce a kink?

A

It shows no rotation, and it is cis.

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16
Q

Are all principle phospholipids charged?

A

No, only phosphatidylserine, which has a net negaytive charge.

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17
Q

Describe the order of permeability of difference substance across a lipid bilayer.

A

Most permeable to least permeable:

  • Hydrophobic molecules (O2, N2, CO2)
  • Small, uncharged, polar (H2O, Urea, Glycerol)
  • Large, uncharged, polar (Glucose, Sucrose)
  • Ions (Na+, K+)
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18
Q

What is the term for phospholipids being both hydrophilic and hydrophobic?

A

Amphipathic

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19
Q

What are some pieces of evidence for the bilayer arrangement of phospholipids in cell mambranes?

A

1) Electron microscopy with osmium tetroxide -> Reacts with hydrophilic heads to give a black precipitate
2) Calculations -> E.g. counting the number of phosphilipids in a RBC and calculating the only way they could possibly be arranged in this surface area

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20
Q

What are the two models of neurotransmitter release at a synpase?

A
  • Full fusion -> Everything released
  • Kiss-and-run -> Just touches the membrane and only releases a bit of contents before jumping back
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21
Q

In one word, describe how phospholipids are arranged in a lipid bilayer.

A

Asymmetrically

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22
Q

Describe the charges on a phospholipid bilayer and how this arises.

A
  • Inside is more negative
  • Because all of the phosphatidylserine (PS) is on the inside layer -> This is negatively charged due to its head group
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23
Q

What occurs when a cell membrane loses asymmetry and why?

A
  • Cell death can occur
  • Because phosphatidylserine moves to the outside and can be recognised by phagocytes that destroy the cell
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24
Q

How is lipid assymtery maintained?

A

Phospholipid transfer proteins:

  • Scramblases -> Both directions
  • Flippase -> Outer to inner
  • Floppase -> Inner to outer

The flippase and floppase require ATP to function.

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25
Q

Which way does flippase move phospholipids?

A

Outer to inner

(REMEMBER: FlIppase = Inwards)

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26
Q

Which way does floppase move phospholipids?

A

Inner to outer

(REMEMBER: FlOppase = Outwards)

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27
Q

What is the purpose of lipid asymmetry?

A
  1. Different proteins function better when surrounded by different phospholipids -> Asymmetric protein distribution could lead to asymmetric lipid distribution
  2. Localises proteins through protein-lipid binding
  3. Lipids on the inner side of the plasma membrane are used to derive signalling molecules that function in the cytoplasm
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28
Q

What are the different types of protein in a cell membrane?

A

Examples:

  • Channels
  • Carriers
  • Receptor proteins
  • Cell-adhesion proteins -> Enable cells to attach to ECM
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29
Q

What are the two ways in which a protein may associate with the plasma membrane?

A
  • Integral -> Permanently within the membrane by adding a fatty acid chain or anchor
  • Peripheral -> Temporarily bound by non-covalent linkage
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30
Q

Do proteins and lipids move within the membrane or are they static?

A

They move within the membrane.

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31
Q

Describe an experiment to demonstrate that the plasma membrane is fluid.

A
  • Mouse cell and human cell are fused into a heterokaryon (cell containing genetically different nuclei)
  • Different antibodies are prepared for the proteins from each cell
  • The heterokaryon is incubated for 40 minutes
  • The membrane proteins can be seen to have moved around and mixed with each other
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32
Q

Describe how the movement of a protein in an organism can be studied.

A
  • The gene for the protein can be modified by inserting a sequence that codes for a Green Fluorescent Protein (GFP)
  • When the protein is produced, it is tagged with a green fluorescent marker that can be
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33
Q

Give some examples of when cells might not want the proteins in the plasma membrane to move.

A
  • Post-synaptic membrane receptors
  • Polarised cells such as epithelial cells of the gut
34
Q

How can the movement of proteins in the plasma membrane be restricted?

A
  • Scaffolding proteins
  • Lipid rafts (controversial existence)
35
Q

Give an example of scaffolding proteins.

A

Ankyrin is a scaffolding protein that links integral membrane proteins to the cell cytoskeleton.

36
Q

Give the clinical relevance of protein localisation within the membrane.

A

Heart failure:

  • In healthy cardiac myocytes, calcium channels are arranged in a regular pattern
  • But this structure can be disturbed by heart failure
37
Q

Describe some examples of the lateral heterogenity of membranes.

A
  • Lipid rafts -> Sections of the membrane with a high concentration of cholesterol and glycosphingolipids -> Examples include small invaginations called caveolae
  • Multiprotein complexes -> A form of quaternary structure where several proteins associate non-covalently
  • Signalling domains -> Allow communication from outside of the cell to inside it
38
Q

Give some examples of the functions of integral cell membrane proteins.

A
  • Receptors
  • Transporters
  • Enzymes
  • Adhesion molecules (e.g. for adhesion to ECM and other cells)
39
Q

What type of cell membrane protein do receptors tend to be?

A

Transmembrane

40
Q

Give two examples of adhesion molecules within a cell membrane.

A
  • Integrins -> For attachment to the ECM
  • Cadherins -> For attachment to other cells
41
Q

What type of molecule is cholesterol?

A

An unsaturated alcohol (sterol).

42
Q

What is the function of cholesterol within the cell membrane?

A
  • It affects the fluidity of the membrane -> Allowing for association of components
  • At high temperatures, it stabilizes the membrane and raises its melting point
  • At low temperatures it intercalates between the phospholipids and prevents them from clustering together and stiffening
43
Q

Give some examples of the functions of peripheral (extrinsic) cell membrane proteins.

A
  • Components of the cytoskeleton that hold membrane components in place
44
Q

What are some functions of glycoproteins and glycolipids in cell membranes?

A

They predominantly act as cell markers. They may also have a role in cell membrane stability.

45
Q

Potassium Sodium Chloride Phosphate Calcium Hydrogencarbonate Protein Magnesium

Describe which cations and anions have higher concentration intracellularly and extracellularly.

A

Higher intracellularly:

  • Potassium
  • Phosphate
  • Protein
  • Magnesium
  • Hydrogen

Higher extracellularly:

  • Sodium
  • Chloride (NOTE: Varies a lot intracellularly)
  • Calcium
  • Hydrogencarbonate
46
Q

Give the main ways in which transport across membranes can occur.

A
  • Vesicles
  • Through the lipid bilayer
  • Proteins -> Channels, Carriers, Pumps
47
Q

Give the order of the permeability of different species across a lipid bilayer.

A

From most to least permeable:

  • Small, non-polar
  • Small, uncharged, polar
  • Large, uncharged, polar
  • Ions
48
Q

If a species can move across a cell membrane by diffusing through the cell membrane, can it still be transported by proteins too?

A

Yes

49
Q

What is solute partitioning?

A

Partitioning is the distribution of a solute between two immiscible solvents (such as aqueous and organic phases).

50
Q

Give the equation that describes the process of partitioning during diffusion across a lipid bilayer in a cell membrane.

A

[solute]lipid = [solute]water x alipid solubility coefficient

51
Q

What does Fick’s Law describe?

A

The rate at which a solute will dissolve across a cell lipid bilayer.

52
Q

State Fick’s Law.

A

J = D x A x (ΔC/Δx)

Where:

  • J = Diffusion flux
  • D = Diffusion coefficient -> Depends on molecular weight and temperature
  • A = Surface area
  • ΔC = Concentration difference
  • Δx = Membrane thickness
53
Q

What is electrodiffusion?

A

The diffusion of ions due to the charge gradient across a membrane.

54
Q

What is the tonicity of a solution?

A

The osmotic force exerted by the solution.

55
Q

What is the normal body fluid osmotic potential?

A

300mOsm/L

56
Q

What increases the water permeability of membranes?

A

Aquaporins

57
Q

What are channels?

A
  • Aqeuous-filled pores
  • Allow the (often selective) transport of ions and some osmolytes across the membrane by passive diffusion
58
Q

Name the different types of channel.

A

Always open:

  • Leak

Gated:

  • Voltage-gated
  • Ligand-gated
  • G-protein-coupled
  • Stretch-activated
59
Q

What makes transport proteins (channels and carriers) specific?

A

There is an interaction between the solute and the transport protein.

60
Q

Give some examples of voltage-gated channels.

A
  • Voltage-gated sodium channel
  • Voltage-gated potassium channel
  • Voltage-gated calcium channel
61
Q

Give some examples of ligand-gated channels.

A
  • ACh receptor
62
Q

Describe simply the functioning of G-protein coupled receptors.

A
  • Ligand binds to receptor
  • This causes the release of a G-protein
  • This either directly or via an effector protein causes a change in the channel
63
Q

How does transport via carriers differ from channels?

A

Transport via carriers is:

  • Slower
  • More sensitive to temperature
  • Saturable (with Vmax and Km)
64
Q

What are gap junctions and what is their structure?

A
  • Non-selective channels between cells that allow intercellular electrical and chemical communication
  • Formed of two aligned connexons (each made of 6 connexins)
65
Q

What is active transport?

A

The movement of substances against their electrochemical gradients.

66
Q

Describe the change that occurs when a carrier moves a substance across the membrane.

A

The binding of the ligand causes a cyclical conformational change that releases the ligand on the other side.

67
Q

What are the types of carrier?

A
  • Primary active -> Use energy from ATP to move substances against their electrochemical gradient
  • Secondary active -> Use the energy from an electrochemical gradient set up by another primary active transporter to move substances against their electrochemical gradient
  • Facilitated diffusion -> Speed up the equilibriation of substances, but cannot move them against electrochemical gradients
68
Q

Do membrane transporter include channels?

A

NO, transporters do not include channels.

69
Q

Give an example of primary active transporters.

A
  • Na+/K+-ATPase
  • Ca2+-ATPase
  • H+/K+-ATPase (used to acidify the stomach)
70
Q

Give an example of secondary active transporters.

A
  • Na+/Ca2+ exchanger
  • Sodium-glucose symporter
71
Q

Draw the action of a sodium-potassium pump.

A
72
Q

Give an example of a facilitated diffusion passive carrier.

A
  • GLUT transporter
  • AE1 (‘chloride shift’)
73
Q

What are the different types of secondary active transporter? Give an example of each.

A
  • Symporter -> Move substances in the same direction (e.g. Sodium-glucose and sodium-amino acid)
  • Antiporter -> Move substances in opposite directions (e.g. Sodium-calcium and sodium-hydrogen)
74
Q

Describe the arrangement of transporters in epithelial cells.

A
  • Epithelial cells are polarised.
  • In the small intestine, the membrane on each side contains different transporters.
75
Q

State the extracellular and intracellular concentrations for sodium ions.

A
  • Intracellular = 140mM
  • Extracellular = 5-15mM
76
Q

State the extracellular and intracellular concentrations for potassium ions.

A
  • Extracellular = 4mM
  • Intracellular = 140mM
77
Q

State the extracellular and intracellular concentrations for calcium ions.

A
  • Extracellular = 2.4mM
  • Intracellular = 0.1 micromolar
78
Q

State the extracellular and intracellular concentrations for chloride ions.

A
  • Extracellular = 100mM
  • Inracellular = Less than extracellular, but varies a lot
79
Q

State the extracellular and intracellular concentrations for bicarbonate ions.

A
  • Extracellular = 25mM
  • Intracellular = 10-20mM
80
Q

State the extracellular and intracellular concentrations for hydrogen ions.

A
  • Extracellular = 40nM
  • Intracellular = 50-100nM

YEAR 1 - Physiology and Pharmacology (Anton) (13 decks)

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