1 - Membrane Transport Flashcards
What is osmosis?
The movement of water across a SELECTIVELY permeable membrane
What direction will water flow across a selectively permeable membrane?
Water will move from high concentration of water to low concentration of water
What does semi-permeable mean?
Water (the solvent) can diffuse through a membrane that is impermeable to the solute
What is necessary for a membrane to be permeable to water?
It must contain aquaporins
What determines the rate of osmosis?
The number of aquaporin channels
When then number of aquaporin channels increases, the rate of osmosis increases
What is simple diffusion?
The movement of a substance from an area of high concentration of that substance to an area of low concentration of that substance
What types of particles can pass through a membrane by simple diffusion?
- Gasses such as O2 and CO2
- Small, uncharged polar molecules
What does simple diffusion only work for those types of molecules?
Because of the hydrophobic core of the phospholipid bilayer, it is mostly impermeable to water-soluble molecules and ions
What is another name for facilitated diffusion?
Carrier-mediated
What is facilitated diffusion?
Protein-mediated transport of a SINGLE type of molecule, such as glucose or other small hydrophilic molecules, down a concentration gradient across a cellular membrane
What are uniporters?
Proteins that transport only one substance
Example: Facilitated transport of glucose
What 8 factors control SIMPLE diffusion through a membrane?
1 - Lipid solubility 2 - Molecular size 3 - Cell membrane thickness 4 - Concentration gradient 5 - Membrane surface area 6 - Composition of lipid bilayer 7 - Temperature 8 - Pressure difference across the membrane (special cases)
How does lipid solubility control SIMPLE diffusion through a membrane?
Increased lipid solubility is associated with an increased permeability of the lipid bilayer
How do you know the lipid solubility of a substance?
The lipid solubility of a substance can be indicated by the oil-water partition coefficient of the substance
How does the molecular size of the diffusing substance control SIMPLE diffusion through a membrane?
As molecular size (molecular radius OR molecular weight) of the diffusing substance increases, the rate of diffusion decreases
How does the cell membrane thickness control the SIMPLE diffusion through a membrane?
The rate of diffusion decreases as the thickness of the membrane increases
How does pneumonia change the rate of SIMPLE diffusion through a membrane?
Pneumonia has a disease process that increases the diffusion distances (makes the membrane thickness greater), which decreases the rate of diffusion
How does the concentration gradient control the SIMPLE diffusion through a membrane?
The greater the difference in concentration, the faster the rate of net diffusion
Substances ALWAYS diffuse down their concentration gradient
How does the membrane surface area control the SIMPLE diffusion through a membrane?
The larger the surface area, the larger the rate of net diffusion
How does temperature control the SIMPLE diffusion through a membrane?
In general, substances diffuse more rapidly as the temperature is raised
How does the pressure difference across the membrane control the SIMPLE diffusion through a membrane?
Hydrostatic pressure differences are important for transport through capillary walls and will be discussed later in renal
What 4 factors control diffusion through pores or channels in the membrane?
1 - Permeability
2 - Selectivity
3 - Concentration gradient
4 - Aquaporins
How does permeability control diffusion through pores or channels in the membrane?
Number of channels, percentage of open channels, etc.
How does selectivity control diffusion through pores or channels in the membrane?
The physical structure of the channel and the distribution of charges in the channel can control which ions can move through the channel
How does the concentration gradient control diffusion through pores or channels in the membrane?
Electrochemical concentration gradient in the case of ions
How do aquaporins (AQPS) control diffusion through pores or channels in the membrane?
The permeability of aquaporins may be modulated by various factors including pH
Water movement through aquaporins can be regulated by insertion or removal of the proteins from the cell membrane
Describe the role of aquaporins (AQPS)
Aquaporins are proteins that form water channels through the cell membrane
The rate of osmosis increases when the number of water channel aquaporins in the membrane is increased
What 3 factors influence the rate of FACILITATED diffusion through uniporters?
1 - Number of transporters
2 - Concentration gradient
3 - Substance affinity for transporter
How does the number of transporters influence the rate of FACILITATED diffusion through uniporters?
- Transport occurs via a limited number of uniporter molecules
- This means there is a maximum rate (Vmax) that depends on the number of uniporters in the membrane
Vmax is achieved when the concentration gradient across the membrane is very large and each uniporter is working at the maximal rate
How does the concentration gradient influence the rate of FACILITATED diffusion through uniporters?
Since the transport direction through uniporters is reversible, the direction of transport will change if the direction of the concentration gradient changes
How does the substance affinity for the transporter influence the rate of FACILITATED diffusion through uniporters?
Km is a measure of the affinity a transporter and substance have for each other (it is a transporter-substance constant)
How do you measure Km?
Km is measure by HALF of the concentration of a substrate at which the transporter is function at HALF its maximal capacity
What are the limitations of uniporters in FACILITATED diffusion?
- Uniporters CANNOT transport uncharged substances against the concentration gradient
- Uniporters CANNOT transport ions against electro chemical potential gradients
What is the difference between facilitated diffusion and active transport in terms of the carrier molecule?
Facilitated - requires a carrier protein
Active - requires a special carrier molecule
What is the difference between facilitated diffusion and active transport in terms of the rate of transport
Facilitated - speed depends on concentration gradient and the maximum rate is limited by the number of channels
Active - will also have a determined rate maximum
What is the difference between facilitated diffusion and active transport in terms of the specificity
Facilitated - transport of a substrate is specific based on the type of molecule (it is limited to a single type or a single group of closely related molecules)
Active - transport of a substrate is specific based on the chemical properties of the substrate and the sterospecificity
What is the difference between facilitated diffusion and active transport in terms of the competition
Facilitated - does NOT demonstrate competition between different molecules because it is specific for only one
Active - demonstrates both competitive and non-competitive inhibition
What is the difference between facilitated diffusion and active transport in terms of the energy requirement
Facilitated - does NOT require energy
Active - requires energy, which is acquired through the hydrolysis of ATP or another high every phosphate compound
What is the difference between facilitated diffusion and active transport in terms of the transport of uncharged substances?
Facilitated - cannot transport uncharged substances against the concentration gradient
Active - can transport uncharged substances against a concentration gradient
What is the difference between facilitated diffusion and active transport in terms of the transport of ions
Facilitated - cannot transport ions against an electrochemical potential gradient
Active - can transport ions against an electrochemical potential gradient
What does uniport mean?
A carrier transports only one substance
Example: facilitated transport (or carrier-mediated diffusion) of glucose
What does carrier-mediated transport mean?
Requires that two or more substances be moved through the membrane together
What does symport mean?
Two or more substances transported in the SAME direction (AKA co-transprot)
What does antiport mean?
Two or more transported substances move in OPPOSITE directions though a membrane
What are ABC transporters?
ATP binding cassettes
ABC transporters are utilized in primary ACTIVE transport and all have a common ATP-binding domain (the cassette).
How do ABC transporters get energy for active transport?
Some ABC proteins (but not all) hydrolyze ATP to provide energy for solute transport.
What is the function of the ABC proteins that do NOT hydrolyze ATP for energy?
- Some do not hydrolyze ATP but the ATP regulates the ABC protein function
- Some ABC proteins actually act as an ion channel or regulate ion channels or transporters
What are two examples of ABC proteins that are clinically relevant?
CFTR protein
MRD protein
Describe the clinical relevance of the CFTR protein
- CFTR (cystic fibrosis transmembrane conductance regulator) is a member of the ABC superfamily
- CFTR functions as a low-conductance Cl-channel and a regulator of other channels
- Opening and closing of the channel is controlled by the binding of ATP to the CFTR
- Mutations in the gene for CFTR causes cystic fibrosis
What are MDR protiens?
Multi-drug resistance proteins
Describe the clinical relevance of MDR proteins
- When these ABC transporters are overexpressed in tumors, they cause resistance to cnacer drug therapy
- The cancer drug is transported out of the cancer cell before it can kill the cell
Describe endocytosis
The plasma membrane invaginates, or folds inward, forming a vesicle that brings substances into the cell
Describe exocytosis
Material inside the cell is packaged into vesicles which are then excreted from the cell into the extracellular medium
What are some examples of clinically relevant exocytosis?
- Release of neurotransmitters at a synapse
- Release of hormones by endocrine cells
What are the 5 types of endocytosis?
1 - Phagocytosis 2 - Pinocytosis 3 - Fluid-phase endocytosis 4 - Receptor-mediated endocytosis 5 - Caveolae endocytosis
What is phagocytosis?
A type of endocytosis described as “cell eating” - it is only done by specialized cells such as macrophages and neutrophils
What is pinocytosis?
A type of endocytosis described as “cell drinking” - ALL cells perform pinocytosis
What is fluid-phase endocytosis?
This is the random uptake of materials that are dissolved in the extracellular fluid that surrounds a cell
Are the materials imported into the cell by fluid-phase endocytosis bound to receptors?
NO - the import consists of random materials in the extracellular fluid
Do all types of fluid-phase endocytosis involve the utilization of the protein clathrin?
No, but some types do
Describe the steps of fluid-phase endocytosis with the utilization of clathrin
- A clathrin cage assembles on the cytoplasmic side of the membrane
- The clathrin cage is attached to the membrane via interactions with adaptin proteins
- Adaptin proteins are adheared to the cytoplasmic tail domains of certain transmembrane polypeptides
- The adherent membrane invaginates into the clathrin cage, forming a coated pit
- Once the clathrin cage is completed, the closed vesicle detaches from the cell membrane
Does the formation of the clathrin cage require energy?
No - the formation of the clathrin cage is spontaneous and energetically favorable
I thought endocytosis required energy though… Which stage of this process requires ATP?
Once the vesicle has detached from the cell membrane, the clathrin cage is removed through the actions of special cytoplasmic enzymes that use the energy of ATP to disassemble the clathrin cage
Is the fluid-phase endocytosis an efficient way to transport a specific substance into the cell?
No - very inefficient because of the randomness of the selection for import
How much target substance is brought into the cell via fluid-phase endocytosis?
Not much… Most target substances are at a low concentration in the extracellular fluid and not much fluid is brought into the cell via a vesicle
What is receptor-mediated endocytosis?
This method of endocytosis can concentrate specific receptor proteins to the site of endocytosis for selective import into the cell
How do the receptors form at the site of endocytosis?
The receptor proteins have cytoplasmic tails that bind to adaptins that in turn associate with clathrin
How do the receptors work?
- At the clathrin cages for coated pits, the receptor proteins are included in the selection of membrane that becomes the endocytotic vessel
- Thus the substance bound to the receptor is transported into the cell
Do the receptor proteins bind to the adaptin before or after they have found their substrate?
It depends on the receptor…
- Some receptor proteins bind to their adaptins whether or not they have bound to their ligand
- Some receptors only interact with their adaptins when the receptor is in the bound state
Why is the receptor-mediated method of endocytosis clinically important?
- Receptor-mediated endocytosis is important for the transport of low-density lipoprotiens and associated cholesterol into the cells
What happens when individuals lack LDL receptors or have defective LDL receptors?
They have high levels of cholesterol-laden LDL in their blood - this predisposes these people to developing atherosclerosis and heart disease
What is caveolae endocytosis?
A similar process to clathrin-mediated endocytosis, but the process uses caveolae and caveolin as the coated protein
What are caveolae?
Well defined invaginations in the plasma membrane (diameter of about 100 nm), which are considered to be a special type of “lipid raft”
How is the caveolae composition different from other lipid rafts?
These lipid rafts are stabilized by the protein caveolin
What is the major role of caveolae?
The uptake of material into cells via caveolae-mediated endocytosis
Why is clathrin important for fluid-mediated and receptor-mediated endocytosis?
Clatherin cages and coated pits are energetically favorable and form readily, meaning that they initiate the process of endocytosis in both fluid-phase endocytosis and receptor-mediated endocytosis
