VS2: Cellular homeostasis (1) Flashcards
What are the two types of proteins that mediate transmembrane transport?
Channel protiens
Carrier protiens
What is the main difference in how channel and carrier proteins work?
Channel proteins form a hole in the membrane, allowing molecules to move through
Carrier proteins undergo a transformational change to allow molecules across
What are the similarities and differences between facilitated and simple diffusion?
Similarities
- Both are passive (i.e. move solutes down an electrochemical gradient from high concentration to low concentration)
Differences
- Facilitated diffusion can be saturated, whereas simple diffusion depends linearly on solute concentration
- Facilitated diffusion is more temperature-dependent because it is protein-dependent
What is the permeability coefficient?
The rate of transport of water
Is water generally considered to be membrane-permeable or -impermeable?
Generally membrane-permeable
Where in the body is there low H2O permeability?
Ascending loop of Henle (especially the thick limb)
Where in the body is there a high H2O permeability?
Red blood cells, renal proximal-tubule cells
On what does the water permeability of membranes depend?
-
Lipid composition
- Unsaturated phospholipids increase membrane fluidity ∴ more permeable to water
- Sterol content (e.g. cholesterol) decreases membrane fluidity ∴ less permeable to water
- This explains why artificial lipid bilayers have varying permeabilities
- Water pores (aquaporins)
What are aquaporins?
Transmembrane proteins that allow water to pass through their pore
What is the structure of an aquaporin?
- Transmembrane protein
- Consists of four subunits ∴ tetrameric protein
- Each subunit has six α-helical transmembrane regions arranged in a ring, forming a transmembrane pore
What is the transport rate of an aquaporin?
Up to 109 molecules/sec
How many pores does each aquaporin have, and what is the diameter of these pores?
4 pores per aquaporin
2.8 Å
What is the diameter of a water molecule? How is this relevant?
Approx. 2.75Å
The diameter of a pore in an aquaporin is 2.8Å so a water molecule fits perfectly through the pore
How many subtypes of aquaporin are there? Are they all only permeable to water?
12
No – others can be permeable to small molecules such as glycerol (aquaglyceroporins)
How can pH modulate the permeability of an aquaporin?
A change in pH alters the ionic states of amino acids in an aquaporin, causing a small conformational change
How is the direction of movement of ions through ion channels determined?
By the electrochemical gradient
By what can ion channels be gated? What is the name for these types of ion channels?
- Membrane voltage – voltage-gated channels
- Extracellular/intracellular messengers – ligand-gated channels
- Mechanical stress – sensory channels/mechanosensitive channels
How do solute carriers work?
- A solute binds to the solute carrier on one side of the membrane
- The protein undergoes a conformational change
- The solute is released on the other side of the membrane
- The protein undergoes another conformational change and returns to its original shape
What are the names for solute carriers that transport glucose?
GLUT1 – GLUT4
What are the similarities and differences between channels and carriers?
Similarities
- Both are passive (do not require ATP)
Differences
- Carriers undergo a conformational change for each molecule they transport, whereas channels only change conformation when opening/closing
What drives passive transport?
The concentration gradient
What is active transport and what drives it?
The movement of a solute against a concentration gradient, driven by energy (ATP)
What are the two forms of active transport?
Primary and secondary
What is primary active transport?
Active transport using hydrolysis of ATP to generate energy for transport, e.g. ATP-dependent transporters (pumps)
What are the three subtypes of ATPase ion transporters?
-
P-type (pump)
- e.g. Na+/K+-ATPase
- V-type (vesicular)
- F-type
How do P-type ATPase ion transporters work?
ATP hydrolysis leads to phosphorylation causing a conformational change
Where are V-type ATPase ion transporters found?
Synaptic vesicles and cytoplasm
How do F-type ATPSase ion transporters work?
They use proton gradients for ATP synthesis in mitochondria
How many domains are there in Na+/K+-ATPase and what are they?
Four:
- N – nucleotide-binding (ATP-binding) domain
- P – phosphorylation domain
- A – actuator domain
- M – transmembrane domain
How does Na+/K+-ATPase work?
- Resting state: 3 Na+ ions bind from the intracellular space
- ATP binds, causing a conformational change
- 3 Na+ ions are released into the extracellular space
- 2 K+ ions bind from the extracellular space
- Na+/K+-ATPase returns to the resting state, releasing 2 K+ ions into the intracellular space
What are the common features of ABC transporters?
- ATP-binding cassette
- Usually homodimer (2 identical subunits)
- Each subunit consists of:
- transmembrane domain
- nucleotide-binding domain
What is the mode of action of ABC transporters?
- Open dimer has high ligand affinity so ligand binds
- Ligand binding increases ATP affinity so ATP binds to two subunits
- Conformational change reduces ligand affinity so ligand released
- ATP is hydrolysed and released, so transporter returns to open configuration
What is co-transport? Give an example.
The movement of two or more solutes in one transport cycle of the same carrier
e.g. Na+/K+-ATPase
What are the two types of co-transport? Define them and give an example of each.
-
Symport
- Both solutes are transported in the same direction
- e.g. Na+ and glucose
-
Antiport
- Solutes are transported in opposite directions
- e.g. Na+/K+-ATPase
What is secondary active transport?
The energy from the movement of solute A down its electrochemical gradient drives the co-transport of solute B against its electrochemical gradient
Is this symport or antiport? What is the energy source?
Symport
Energy source = Na+ gradient
Is this symport or antiport? What is the energy source?
Symport
Energy source = Na+ gradient
Is this symport or antiport? What is the energy source?
Symport
Energy souce = Na+ gradient
Is this symport or antiport? What is the energy source?
Symport
Energy source = K+ gradient
Is this symport or antiport? What is the energy source?
Antiport
Energy source = Na+ gradient
Is this symport or antiport? What is the energy source?
Antiport
Energy source = Na+ gradient
Is this symport or antiport? What is the energy source?
Antiport
Energy source = Cl– gradient
What is the transport mode and rate of a water channel?
Pore (gated)
Up to 109 molecules per second
What is the transport mode and rate of an ion channel?
Gated
106 – 108 molecules per second
What is the transport mode and rate of a solute carrier?
Cycle
102 – 104 molecules per second
What is the transport mode and rate of an ATP-dependent channel?
Cycle
102–104 molecules per second
