MCB 5: Transport Across Cell Membranes Flashcards

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1
Q

What is the purpose of a plasma membrane?

A
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2
Q

Why do we need specialised systems for transport across cell membranes?

A
  • the hydrophobic interior of the lipid bilayer creates a barrier for most hydrophobic molecules, including all ions
  • therefore, cells can maintain concentrations of solutes that differ from those in the extracellular fluid, and in intracellular compartments
  • however, cells and organelles need to exchange many hydophilic, water-soluble molecules by transporting them across membranes
  • these molecules are transported by specialised membrane transport proteins, by a process called facilitated transport
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3
Q

What type of molecules are able to cross a pure lipid bilayer and which cannot?

A
  • small, non polar molecules, such as O2 and CO2 dissolve readily in lipid bilayers and diffuse across them without any help
  • small uncharged polar molecules, such as water or ethanol also diffuse across the bilayer
  • larger uncharged polar molecules, such as glucose cross hardly at all
  • charged molecules, including all inorganic ions, cannot cross the lipid bilayer, no matter how small
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4
Q

How is facilitated transport enabled?

A
  • cell membranes contain specialised transport proteins, each of which transports a particular type of molecule
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5
Q

How do transmembrane proteins cross the membrane?

A
  • transmembrane proteins extend through the lipid bilayer
  • part of their polypeptide chains are found on either side of the membrane
  • these proteins cross the membrane with hydrophobic segments of their polypeptide chains, which are known as transmembrane domains
  • they either cross the bilayer as a single alpha-helix, as multiple alpha-helices, or as a different structured formed by a rolled-up beta-sheet (beta-barrel)
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6
Q

How do transmembrane proteins form channels across cell membranes?

A
  • some transmembrane proteins function as channels by forming pores
  • channel proteins form aqueous (water-filled) pores across the lipid bilayer, that allow small, water-soluble molecules to cross the membrane
  • these are formed by transmembrane proteins with several alpha-helices that cross the bilayer a number of times
  • the alpha-helices are arranged so that a central, hydrophilic pore is formed, while hydrophobic parts of the alpha-helices pack side-by-side in a ring that faces the lipids of the membrane
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7
Q

What are the two main classes of specialised membrane transport proteins and what are their similarities?

A
  • transporters
  • channels
  • both types have polypeptide chains that traverse the lipid bilayer multiple tmes
  • they form aqueous channels across the membrane, and allow specific hydrophilic solutes to cross the membranre without coming into direct contact with the hydrophobic interior of the lipid bilayer
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8
Q

What are the characteristics of transporter proteins?

A
  • a transporter transfers only those molecules that fit into a specific binding
  • it undergoes a series of conformational changes to transfer small molecules across the lipid bilayer
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9
Q

What are the characteristics of channels?

A
  • a channel discriminates the molecules it transports mainly on their size and charge
  • when the channel is open, any ion or molecule that is small enough and carries the appropriate charge will pass through
  • channels form pores that extend cross the membrane
  • these pores allow the diffusion of specific inorganic ions (or in some cases, small, polar organic molecules)
  • ion channels exist in open and closed conformations
  • when open, the pores allow specific solutes to pass through them and so cross the membrane
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10
Q

What determines whether molecules move into the cell or out of the cell?

A
  • direction of transport depends on the relative concentration of the molecule on either side of the membrane
  • molecules will spontaneously flow from a region of high concentration to a region of low concentration
  • these movements are passive because they don’t need additional energy
  • if a solute has to be transported from a region of low concentration to a region of high concentration, additional energy is required and this is active transport
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11
Q

What type of transport do channels and transporters carry out?

A

Simple diffusion:

  • small, non-polar molecules can move down the concentration gradient by simple diffusion

Ion Channels:

  • mediate passive transport
  • as long as the ion channel is open, appropriate ions will move down their concentration gradient by passive transport
  • ion channels cannot mediate active transport

Transporters:

  • they can mediate passive transport (known as facilitated diffusion) if the molecules move down their concentration gradient
  • special transporters called pumps can mediate active transport to move a molecule against its concentration gradient
  • requires energy and done by coupling the transport to some other process that provides an input of energy
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12
Q

Briefly describe the ion concentrations in and out of cells

A
  • Na+ is the most common positively charged ion (cation) outside the cell
  • K+ is the most abundant cation inside
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13
Q

How are charges balanced in cells and their surrounding fluids?

A
  • the quantity of positive charge is balanced by an almost equal quantity of negative charge (both inside the cell and in the surrounding fluid)
  • the high concentration of Na+ outside the cell is mainly balanced by Cl-
  • the high concentration fo K+ inside the cell is balanced by different negatively charged organic and inorganic ions (anions)
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14
Q

What is the membrane potential?

A
  • the membrane potential is created by small differences in the concentration of inorganic ions across the cell membrane
  • while electrical charges inside and outside cells are generally balanced, tiny excesses of positive or negative charge occur near the plasma membrane
  • these electrical imbalances create a voltage difference across the plasma membrane (membrane potential)
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15
Q

Why do most cells have a negative membrane potential?

A
  • most cells have more negative charge inside the cells compared to outside the cell
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16
Q

What influences passive transport in electrically charged molecules (inorganic molecules or small organic molecules with a charge)?

A
  • as well as the concentration gradient, the membrane potential also influences passive transport in electrically charged molecules
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17
Q

How does the membrane potential generally affect electrically charged molecules

A
  • the membrane potential exerts a force on any molecule with an electrical charge
  • as the cytosolic side of a cell usually has negative membrane potential relative to the extracellular side, so the membrane potential tend to pull positively charged solutes into the cell and drive negatively charged ones out
  • it also opposes the outward flow of positively charged ions
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18
Q

What is the definition of a solute’s electrochemical gradient?

A
  • the solute’s electrochemical gradient is the net force driving a charged molecule across a cell membrane
  • the net force is comprised of two forces: one due to the concentration gradient and the other due to the membrane potential
19
Q

Does Na+ tend to enter or leave the cell?

A
  • Na+ tends to enter the cell, if given the opportunity
  • generally, Na+ has a higher concentration outside the cell than inside
  • here, the concentration gradient and the membrane potential work together to increase the driving force for Na+ to enter the cell
20
Q

Why is there only little movement of K+ across the membrane even if its channels are open?

A
  • K+ has a much higher concentration inside the cell than outside
  • here the membrane potential and the concentration gradients act in opposite directions, resulting in a small electrochemical gradient across the membrane
  • so there is very little movement of K+ across the membrane
21
Q

Describe some characteristics of transporters

A
  • transporters are responsible for the movement of most small, water-soluble, organic molecules and some inorganic ions across cell membranes
  • each transporter is highly selective
  • they exist on the plasma membrane and the membranes of all intracellular organelles
22
Q

Briefly describe plasma membrane transporters, mitochondrial transporters and lysosomal transporters

A

Plasma membrane transporters:

  • plasma membrane contains transporters that import nutrients into the cell, such as nucleotides, sugars and amino acids

Mitochondrial transporters:

  • the inner mitochondrial membrane contains transporters for importing the pyruvate that mitochondria need to generate ATP, as well as transporters for exporting ATP once it is synthesised

Lysosomal transporters:

  • the lysosomal membrane contains a transporter that imports H+ to make the inside of the lysosome more acidic and other transporters that move digestion products out of the lysosome into the cytosol
23
Q

What are co-transporters

A
  • transporters that carry multiple solutes
24
Q

What is a uniport?

A
  • a transporter that only carries one type of solute, selectively bringing it from one side of the membrane to the other
25
Q

What is a symport?

A
  • a co-transporter that carries two types of solutes moving in the same direction across the membrane
  • usually, one solute is carried down its concentration gradient (from high to low)
  • the energy released by the movement of the solute drives the movement of the other solute, against its concentration gradient (from low to high)
26
Q

Describe the antiport

A
  • a co-transporter that moves solutes in opposite directions across the membrane
  • one of the solutes is transported down its concentration gradient, from high to low concentration, which fuels the transport of the other solute, against its concentration gradient
27
Q

Which transporter is which?

A
28
Q

Describe how glucose transporters work and their brief structure then describe how glucose binds after a meal and when blood glucose concentrations are low

A
  • glucose transporters have a polypeptide chain that crosses the membrane 12 times
  • each transporter can adopt several conformation, and it switches randomly between them
  • because glucose is not charged, the membrane potential does not affect it
  • so the direction in which it is transported is determined by its concentration gradient alone
29
Q

Describe the steps of glucose transport

A
  1. Glucose binds to the externally exposed binding site on the transporter
    - each type of transporter transfers the solute across the lipid bilayer by undergoing reversible conformational changes that alternately expose the solute binding site first on one side of the membrane and then on the other
    - but never on both sides at the same time
    - in this case, the binding site is exposed on the outside of the cell
  2. Occluded state
    - the conformation change of the transporter goes through an intermediate state, the occluded state
    - in this state, the transporter’s glucose binding sites are not accessible from either side
  3. Release of glucose
    - after the conformational change, the binding site for glucose is exposed on the inside of the cell
    - glucose is released into the cell
30
Q

What transporters are used for active transport?

A
  • cells use transmembrane transporters that function as pumps
  • these carry out active transport in three ways:
  • coupled transporters: use the energy stored in concentration gradients (or electrochemical gradients) to couple the uphill transport of one solute across the membrane to the downhill transport of another.
  • ATP-driven pumps: couple uphill transport to the hydrolysis of ATP.
  • Light-driven pumps: couple uphill transport to an input of energy from light.
31
Q

Describe how couple pumps carry out active transport

A
  • these pumps link the transport of one molecule against its chemical gradient to the downhill transport of another molecule
32
Q

Describe how ATP-driven pumps carry out active transport

A
  • ATP-driven pumps hydrolyse ATP to drive uphill transport
  • e.g. the yellow molecule will be transported out of the cell against its electrochemical gradient and the energy needed for this comes from ATP hydrolysis
33
Q

Describe how light-driven pumps carry out active transport

A
  • light-driven pumps are mostly found in bacteria
  • they use energy from sunlight to drive uphill transport
34
Q

What is the difference between primary and secondary active transporters

A
35
Q

What is one of the most important pumps in our body?

A
  • the ATP-driven Na+ pump, also known as the Na+/K+ ATPase
  • it plays a central role in the energy cycle of all animal cells
  • it is responsible for 30% or more of a cell’s total ATP consumption
  • the pump uses the energy obtained from ATP hydrolysis to transport Na+ out of the cell while it carries K+ into the cell
36
Q

Use the diagram to help summarise the sodium-potassium pump

A
  • in the cytosol, the sodium ion concentration is kept low relative to the extracellular fluid
  • conversely, potassium ion concentration in the cytosol is kept high
  • sodium ions enter binding sites on the cytosolic side of the pump
  • there are three sodium binding sites on this pump
  • ATP is cleaved to provide energy to pumps sodium against its concentration gradient
  • ATP transfers a phosphate group to the pump in a high energy linkage
  • phosphorylation causes a dramatic change in the pump’s conformation, so that the sodium ions become exposed and released outside the cell
  • this action also exposes two binding sites for potassium ions in the pump
  • binding the potassium ions triggers the release of the phosphate group and the return of the pump to its initial conformation
  • the potassium is then released inside the cell and the cycle repeats
  • each complete cycle takes about 10ms
37
Q

What are ion channels?

A
  • channel proteins that have a narrow central pore that can open and close very quickly
  • each channel is highly selective for a particular inorganic ion
38
Q

What determines the ion selectivity of an ion channel?

A
  • the diameter and shape of the pore
  • the distribution of charged amino acids that line the pore
39
Q

Observe this diagram of an ion channel and pick up the key points

  • this is a bacterial K+ channel
  • has four subunits (green)
A
  • in blue: the pore
  • open into a chamber that sites in the middle of the membrane
  • in aqueous solutions, each ion is surrounded by a small shell of water molecules
  • which have to be shed (removed) for the ion to pass through the pore
  • ions have to move one by one through the narrowest part of the channel
  • the channel is very narrow in places, forcing the ion into contact with the channel wall
  • ensuring only those ions that have an appropriate size and charge are able to pass
  • in this case, the channel is filled with polar groups that form transient bonds with K+ ions
  • once the ion has passed through the channel, a water shell forms again around the ion
40
Q

What are the characteristics of ion channels?

What makes it different from transporters?

A
  • ion channels only open briefly:
  • In order to be able to control the flow of ions, ion channels cannot be open all the time. In fact, they only open briefly, then close again.
  • In the drawing (first) you can see how a typical ion channel fluctuates between the closed and open states.
  • The diagram shows a cross-section across the membrane. You should be able to see that the pore is only formed in the open conformation. No ions can flow through the channel in the closed conformation, as there is no pore formed.
  • Most ion channels are gated, which means that a specific stimulus triggers them to switch between a closed and an open state.
  • unlike transporters, they do not need to undergo conformational changes with each ion, so a large number can pass through the channels
  • More than a million ions can pass through an open ion channel each second, which is 1000 times greater than the fastest known rate of transfer for any transporter.
  • However, unlike transporters, channels cannot couple ion flow to an energy source
  • Ion channels simply make the membrane transiently permeable to selected inorganic ions.
41
Q

What types of stimuli open ion channels?

A

Ion channel types:

  • voltage-gated:
  • pore opening is controlled by a change in voltage difference across the membrane
  • so, influenced by change in membrane potential
  • ligand-gated channels (extracellular ligand):
  • controlled by binding some molecule (the ligand) to the extracellular part of the channel
  • ligand-gated channels (intracellular ligand):
  • controlled by binding of some molecule to the intracellular part of the channel
  • mechanically-gated channels:
  • opening is controlled by a mechanical force applied to the channel
  • allow us to hear
42
Q

What are two ways water can move across cells?

A
  • osmosis:
  • since water molecules are small and not charged, they can move directly across the lipid bilayer, but very slowly
  • aquaporins:
  • some cell types have specialised channels for water transport
  • diffuses rapidly
  • work similarly to the way ions pass through ion channels
  • watch vid in e-module for more detail
43
Q

Describe osmosis

A
44
Q

Descirbe what aquaporins are and their structure

A