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biol 266 > Unit 5: Membrane Transport > Flashcards

Unit 5: Membrane Transport Flashcards

1
Q

What passes through the lipid bilayer easily (+ 4 examples)

A

Small nonpolar molecules (e.g., O2, CO2, N2, Steroid hormones)

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2
Q

Ions like ________ (7 examples) are ______ , but are _________

A

H+, Na+, K+, Ca2+, Cl-, Mg2+, HCO3-

Impermeable through a synthetic lipid bilayer

Permeable to charged molecules (ions)

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3
Q

Small uncharged polar molecules like _______ (3 examples) are______

A

H2O, Ethanol, Glycerol

impermeable through a synthetic lipid bilayer

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4
Q

Large Uncharged polar molecules like _______ (3 examples) are ________, but are __________

A

Amino acids, Glucose, Nucleosides

Impermeable to a synthetic lipid bilayer

Permeable to large uncharged polar molecules

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5
Q

Transfer of water-soluble molecules depends on _______

A

Membrane transport proteins

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6
Q

Each membrane transport protein is ______, which leads to an uneven _______

A

Specific to a particular molecule

Concentration of that molecule to build up on either side of the membrane

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7
Q

Each type of membrane has it’s own characteristic set of

A

transport proteins

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8
Q

What gives the membrane it’s function?

A

Membrane proteins present

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9
Q

Describe the plasma membrane potential.

A

Inside: negative relative charge (high [K+], balanced by nucleic acids and proteins
Inner (cytosolic) leaflet is slightly more -ve

Outside: +ve relative charge (high [Na+], balanced by Cl- ions)
Outer leaflet is slightly more +ve

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10
Q

What contributes to the ion gradient across the plasma membrane

A

Due to specific transporters that move those specific ions

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11
Q

Two ways substances pass through membrane barriers

A
  1. Passive transport ([high] to [low])
  2. Active transport (against concentration gradient, [low] to [high] requires energy)
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12
Q

Passive transport is for what types of molecules?

A

Gases (O2, CO2), hydrophobic molecules and small polar uncharged molecules (H2O, ethanol) can easily dissolve in the lipid bilayer and dissolve in aqueous solution of cytosolic side of membrane

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13
Q

Explain partition coefficient

A

(For non-electrolytes) it is the rate of passive transport/diffusion. Dependent on it’s measure of its ability to partition between aqueous and hydrophobic environments.

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14
Q

A higher partition coefficient will result in

A

A higher speed of diffusion

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15
Q

Two molecules of equal partition coefficient, one is small and one is larger. Which one diffuses faster?

A

The smaller molecule

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16
Q

Direction of transport in passive diffusion is dependent on

A

the concentration gradient only, so molecules move in either direction until reaching equilibrium.

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17
Q

Large polar uncharged molecules (____, _____, and _____) and charged molecules (ions) are ________ in the lipid bilayer

A

Amino acids, nucleotides, sugars

Unable to dissolve

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18
Q

During facilitated diffusion, the passage of polar and charged molecules is ____________ that enable
the transported molecules to cross the membrane without directly ________________.

A

mediated by proteins,
interacting with its hydrophobic interior,

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19
Q

What does facilitated diffusion require and not require?

A

Requires: Membrane proteins + concentration gradient
Does NOT require: Energy (ATP)

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20
Q

Generally describe active transport

A

Moves proteins against their concentration gradient ([low] to [high]).

Requires: Membrane transport protein, coupled with an energy- consuming reaction (ATP hydrolysis).

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21
Q

What does Active transport require?

A

Membrane transport protein (MTP), coupled with ATP-hydrolysis to consume energy

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22
Q

What does the proton pump active transport mechanism in the lysosome do?

A

Generates the low lumenal pH of this lysosome.

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23
Q

What does the sodium/potassium pump of the plasma membrane do?

A

Generates the differences in internal and external Na+ and K+ concentrations.

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24
Q

Three classes of transport proteins

A
  1. ATP powered pumps (primary active transport)
  2. Channel proteins (specific to ions). This is the fastest
  3. Carrier proteins (transporters, going to interact with a solute/ carriers will bind)
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25
Q

Relative speed of transport between the three classes of transport proteins (slowest to fastest)

A

ATP-powered pumps (1-1000 molecules/sec)
Carrier proteins (100-10 000 molecules/sec)
Channel proteins (1E7-1E8 molecules/sec)

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26
Q

ATP-Powered pumps characteristics

A

Couples hydrolysis of ATP to the transport of a molecule against its concentration gradient.

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27
Q

Channel proteins characteristics

A

Transport ions down concentration gradient ([high] to [low]) via hydrophilic pore in the membrane protein.

Exists in open or closed conformation.

Many ions pass simultaneously when open

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28
Q

Carrier proteins (transporters) characteristics

A

Bind to water-soluble (hydrophilic) molecules on one side of the membrane, delivers them to the other side.

Involves a conformational change in the protein.

Only binds to one/a few molecules at a time.

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29
Q

Channels, pumps and carriers can be subdivided into:

A

a) Uniports
b) Symports
c) Antiports

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30
Q

Explain Uniports

A

Work via passive diffusion

Are selective for one type of molecule

Moves molecules down their concentration gradients ([high] to [low]).

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31
Q

What two subdivisions of transport require coupled transport?

A

b) Symport (transported molecule along with co-transported ion go the same direction)

c) Antiport (transported molecule along with co-transported molecule in the opposite directions)

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32
Q

Four differences between uniport and simple diffusion

A
  1. Rate of substance movement = higher for uniports
  2. Partition co-efficient irrelevant for uniports
  3. Uniport transport limited by the number of uniports in the
    membrane
  4. Transport with a uniport is specific.
33
Q

Why is the partition co-efficient irrelevant for uniports?

A

Because there is no contact with the hydrophobic lipid environment

34
Q

Specificity (Km) is a measure of ________

A

The affinity of an enzyme for its substrate. It is the [Solute] to have 1/2 the transporters bound to the substrate.

35
Q

The lower the Km results in

A

Tighter binding to the E-S complex

36
Q

Describe GLUT1 uniporter example (and steps) and what it maintains:

A

The main uniporter for glucose in erythrocytes (blood cells).

Steps:
1. Glucose enters erythrocyte and rapidly converted to G-1-P
2. Can eventually enter glycolysis

Keeps intracellular [Glucose] low, allows for the continuous import of Glucose.

37
Q

In order to have a transporter move protein from [high] to [low], it requires:

A

Structural changes of binding substrate. To do this, you want to be AT OR ABOVE Km concentration to change conformation.

38
Q

Secondary active transport does not

A

Directly use ATP, but uses the effect of ATP to change the conformation of the porter.

39
Q

Symporter and antiporter mechanism

A

(Secondary active transport)

Uses existing electrochemical gradient (rather than direct ATP hydrolysis) to move one of the molecules against its concentration gradient ([low] to [high]) AND a second molecule down its gradient ([high] to [low]).

40
Q

Examples of secondary active transport

A

Re-uptake of NT released by a Na+ symporter
Epithelial Na+/Glucose symporter

41
Q

Secondary active transport via Symport or antiport binding characteristics:

A

Cooperative binding of the two different molecules – the conformational change necessary to deliver the two molecules to the other side of the membrane only happens if/when both are bound to the transporter.

42
Q

Secondary active transport powering mechanism

A

Let something go down gradient to power in opposition to move solute from out to in and the other in to out.

43
Q

Using _______ electrochemical gradient generated by _______, the Na+/Glu symporter can generate internal _________ 3E4x more than external.

A

Na+
Na+/K+ pump
[Glucose]

44
Q

Describe path of Glucose flux in gut epithelial cells

A

Glu (from digested food) arrives from gut lumen (low [Glu]).
The low extracellular (inside cell) [Na+] is due to the Na+/K+ Pump
Glu symport @ apical domain sends Glu into blood for transport to other tissues.

This is partially mediated by tight junction proteins that restrict membrane protein mvmnt.

45
Q

Classes of ATP powered pumps

A
  1. P-class
  2. V-class
  3. F-class
  4. ABC superfamily
46
Q

P-class ATPase (three examples)

A

Heterotetramer w/ 2 subunits: alpha and beta

beta = phosphorylated during transport
(e.g., Na+/K+ ATPase, Ca2+ ATPase, H+/K+ ATPase)

47
Q

V-class ATPase

A

Multiple subunits
Transport only H+ against gradient
Acidifies lysosome & vacuoles

48
Q

F-class ATPase

A

Multiple subunits (related to V-class)
Only one that: Generates ATP and pumps only H+
Found in: Inner membrane of mitochondria, thylakoid, and bacterial plasma membrane

49
Q

ABC superfamily of ATPase

A

Transport sugars, amino acids, phospholipids, proteins
Responsible for multidrug resistance (pumps anti-cancer drugs out of cells)

50
Q

In its E1 conformation, Na+/K+ ATPase has three ______ and two ________ on the ________ surface of the protein.

A

high-affinity Na+ binding sites,
low-affinity K+ binding sites,
cytosolic-facing

51
Q

In Na+/K+ ATPase…
Due to the high _________ of E1 conformation, 3 Na+ ions bind to the Na+ binding sites despite the _______. Despite the high ______, K+ ions are _____________ binding sites. ATP also binds to its site on the ______ side.

A

Na+ binding affinity,
Low intracellular [Na+],
High intracellular [K+],
Unable to bind to the low-affinity K+,
Cytoplasmic

52
Q

In E1 conformation [Solute] ______ Km favours binding, [Solute] ____ Km favours release.

A

Above
Below

53
Q

In Na+/K+ ATPase E1 conformation, [Na+] much higher ________. So a Km that would _______ would be one that is higher.

A

Outside of the cell
Favour release of Na+

54
Q

Na+/K+ ATPase: E1 to E2 conformational change mechanism

A
  1. Na+ and ATP bind on cytosolic side (which has low [Na+] and high [K+])
  2. Bound ATP is hydrolyzed to ADP.
  3. Liberated phosphate transferred to a specific Asp residue on Na+/K+ ATPase, forming a high-energy acyl phosphate bond. ADP is released
  4. Triggers conformational change E1 to E2 ~ high K+ binding affinity and lower Na+ affinity, changes Km.
55
Q

During the E1-E2 transition, the 3 bound Na+ ions become accessible to the _____. Transition E1 to E2 conformation also generates two ______ and three ______ on the______ face. The Na+ ions will ______ and the K+ ions _______ with their high affinity sites.

A

exterior face of the membrane
high-affinity K+ sites
low-affinity Na+ sites
extracellular
Dissociate
Associate (bind)

56
Q

Na+/K+ ATPase: E2 to E1 conformational change mechanism

A
  1. 3 Na+ ions dissociate and and 2 K+ ions associate (bind) on the exterior of the membrane (which has high [Na+] and low [K+])
  2. 3 Na+ released and triggers dephosphorylation.
  3. Liberated phosphate transferred to a specific Asp residue on Na+/K+ ATPase, forming a high-energy acyl phosphate bond. ADP is released
  4. Aspartyl-phosphate bond in E2 = hydrolyzed, ~ E2 to E1 (high Na+ binding affinity and lower K+ affinity, changes Km).
57
Q

During the E2-E1 transition, the _________. The K+ sites revert to _________ sites, thus ______. The transporter is now available for another round of ion transport.

A

2 bound K+ ions become accessible to the cytosolic face,
Low affinity,
Releasing the K+ into the cytosol

58
Q

Explain the Ca2+ ATPase example:

A

Has high affinity Ca2+ binding sites in E1 conformation. Phosphorylation by ATP ~ conformational change that exposes the Ca2+ to the exterior face and lowers the Ca2+ affinity, releasing the ions into the cell exterior. Dephosphorylation regenerates the E1 conformation.

59
Q

Ca2+ ATPase is important in Muscle cells for _____, Nerve cells for ______, Fertilized oocyte to ______, and liver cells for _______.

A

contraction,
NT release,
Start development,
Glycogen breakdown

60
Q

Ca2+ ATPase is important in interface between Smooth ER lumen and Cytosol because:

A

After burst of Ca2+, from the Smooth ER lumen (high [Ca2+]) into the cytosol (low [Ca2+]) needs to move the ion back against its concentration gradient ( [low] to [high]) back to the Smooth ER, which is where Ca2+ tends to be stored.

61
Q

ABC transporters general information and an example:

A

Many members, 2 domains.
ATP hydrolysis opens an ion channel
Ex: CFTR protein

62
Q

Unlike Na/K ATPase, CFTR is simply an….. And what is this process called?

A

Ion channel using ATP to open. Then the Cl- ions move down their concentration gradient ([high] to [low]).

This process is called GATING

63
Q

Health issues with K+/H+ ATPase

A

This membrane transporter is found in parietal cells of the stomach ~ acidic environment.

Drugs targeting: PPI’s.

Acidity also neutralized by basic anions in Tums.

64
Q

Health issues with Na+/K+ ATPase:

A

Inhibition by poison “ouabain”, which alters Na+ gradient and indirectly affects the Na+/Ca2+ exchanger that pumps Ca2+ out of the cells ~ elevated intracellular [Ca2+].

Calcium is an important mediator of muscle contraction so this affects the heart contractions.

65
Q

CFTR (cystic fibrosis transmembrane conductance regulator) general info:

A

Member of ABC superfamily.
It’s not a pump, it’s a transporter of Cl-, coupled to both ATP hydrolysis and ATP binding.

66
Q

CFTR (cystic fibrosis transmembrane conductance regulator) health issues:

A

In lung epithelial cells, water flows out in response to the outward movement of ions, hydrating the mucus layer.

This layer captures bacteria and is easily washed away from the airways.

When CFTR is non-functional, the mucus layer thickens and bacteria accumulate ~ chronic infections.

67
Q

(delta)F508 mutation in CFTR:

A

Deletion of Phe-508.

Protein does not fold at body temperature (37°C) but it does fold and is functional at lower temperature.

VX-809 (small molecule) in clinical trials, binds to CFTR ~ prevents destruction.

68
Q

Advantage of (delta) F508 heterozygosity

A

Protects from cholera & typhoid fever.

Why? The linear protein is inserted in the ER, as the ER is responsible for quality control folding of protein. w/ Phe-508 missing, that ER protein judges it not ready ~ doesn’t pass ER quality control.

It IS functional, though. So if it bypasses the ER quality control system it would be able to be released and functional (perhaps because it is not fully unfolded)

69
Q

Two properties distinguish ion channels from a simple pore in the membrane:

A
  1. Selectivity: Some ions pass, some don’t (depends on diameter, ion shape and charges that line the channel)
  2. Gating: Channels intermittently open, opening in response to a stimulus for short time.
70
Q

Unlike transporters, in ion channels:

A

A conformational change is NOT needed for each ion. More than 1E6 ions can pass through the channel per second (VERY FAST)

71
Q

Three types of Ion channel gating (+1)

A
  1. Voltage-gated: Responds to changes in electric potential across membrane (depolarization opens, repolarization closes)

z2. Ligand-gated: Responds to binding of extracellular ligand first before opening (e.g., NT)

  1. Mechanically-gated: Responds to mechanical force
  2. (+1) CFTR: using ATP to open
72
Q

Na+ ion channels contribute to nerve impulses by:

A

Membrane potential (approx -60mV) from high [Na+] outside of membrane.

When signal input, VGNa+C’s depolarize membrane b/c Na+ will pass +ve charge down [gradient]

@ +40mV, electrical driving force for Na+ is = 0 ~ inactivated state of channels and cannot be stimulated for a time period after.

73
Q

What ensures that the signal moves away one direction from the initial state?

A

Na+ channels close at +40mV when Na+ driving force is = 0 and channels assume inactivated state (3rd conformation), there is a refractory period (absolute and relative) where they can’t fire again.

74
Q

Three conformations of VGNa+ C’s

A
  1. Closed (at rest)
    *AP arrives
  2. Open (membrane depolarized): Na+ floods in
    *Refractory period
  3. Inactivated doesn’t allow Na+ to pass out
    *Recovery and membrane repolarized.
75
Q

Nerve membrane potential is restored by:

A

VG K+ C’s opening AFTER the VG Na+ C’s have opened. Na+ ions flow out.

76
Q

VG K+ C’s do what job effectively

A

Repolarize the membrane potential quickly. If it were just Na+ channels, it would repolarize very slowly.

77
Q

Explain what happens at the synaptic terminals of AP’s in Neuron:

A

Ca2+ channels activated.
Influx of Ca2+ ~ vesicles release of NT in synaptic cleft.

NT’s that fail to bind to postsynaptic R is either: Degraded, or Uptaken by presynaptic membrane.

78
Q

Ionotropic postsynaptic receptors:

A

Receptor is on the ion channel (e.g., ACh receptor)

79
Q

Metabotropic receptors:

A

Receptor is not an ion channel, but signals to the ion channel via an effector protein

biol 266 (9 decks)

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