Questions and Answers
Which of the following transporters has a low affinity for glucose?
In which tissues is GLUT1 abundant and GLUT4 scarce?
What is the primary function of GLUT2 in pancreatic ß-cells?
What is the effect of insulin on GLUT4?
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What is the primary mechanism of ion channel gating?
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What is the effect of insulin on glucose uptake in muscle and adipose tissue?
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What is the primary distinguishing feature of small-molecule transfer across membranes by active transport?
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Which of the following molecules can freely cross the membrane by simple diffusion?
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What is the role of the Na+/K+-ATPase membrane pump?
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Which type of transport requires a membrane protein, such as an ion channel?
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What is the relationship between the Partition Coefficient of a solute and its rate of diffusion?
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What is the function of the GLUT family of glucose transporters?
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What is the significance of the Km in transporter affinity?
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What is the primary difference between facilitated diffusion and active transport?
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Which of the following is an example of secondary active transport?
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What is the term for the selective permeability of membranes to certain molecules?
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What is the primary function of the Na+/K+ pump in nerve cells?
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What type of transport occurs when two solutes move in the same direction across a membrane?
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What is the result of inhibiting the Na+/K+ pump in heart muscle cells?
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What is the function of the CFTR protein in cells responsible for producing mucus, sweat, saliva, and tears?
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What is the purpose of oral rehydration therapy in treating cholera?
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What type of transport is facilitated by the Na+/K+ pump?
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What is the result of the Na+/Ca2+ cotransporter in muscle cells?
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What is the role of the phosphorylation step in the Na+/K+ pump?
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What is the effect of digitoxin on the Na+/K+ pump?
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What is the mechanism by which SGLUT transports glucose into cells?
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Study Notes
Membrane Transport
- Membranes are selective permeability barriers, blocking the passage of almost all hydrophilic molecules into cells and organelles.
- Small uncharged or hydrophobic molecules can freely cross the membrane by simple diffusion along their concentration gradients.
- Charged polar molecules require specialist proteins (pumps, transporters, pores) to allow them to cross the membrane.
Molecules Crossing Membranes
- Hydrophobic molecules that can freely cross the membrane include O2, N2, CO2, benzene, and short-chain fatty acids.
- Small uncharged polar molecules that can cross the membrane include H2O, urea, and glycerol.
- Large uncharged polar molecules that cannot cross the membrane include glucose, sucrose, and ions like H+, Na+, Mg2+, HCO3-, K+, Ca2+, and Cl-.
- Charged polar molecules that cannot cross the membrane include amino acids and ATP.
Mechanisms of Transport
- Passive transport: solutes move down a concentration gradient, crossing the membrane.
- Facilitated diffusion: solutes move down a concentration gradient, crossing the membrane with the help of a transport protein.
- Gated ion channels: ion channels that allow facilitated diffusion, selective for different ions, open or close in response to a stimulus.
- Primary active transport: solutes move against a concentration gradient, requiring energy from ATP hydrolysis.
- Secondary active transport: solutes move against a concentration gradient, using energy from the electrochemical gradient established by primary active transport.
Passive Transport
- Solutes move down a concentration gradient, crossing the membrane.
- At equilibrium, the concentration inside the cell equals the concentration outside the cell.
- The rate of diffusion depends on the partition coefficient of the solute.
- Solutes that are more hydrophobic have a higher partition coefficient and equilibrate more quickly.
Facilitated Diffusion
- Solutes move down a concentration gradient, crossing the membrane with the help of a transport protein.
- Examples include Cl-/HCO3- channel in erythrocytes, aquaporin (water channel), and GLUT glucose transporters.
- The kinetics of transport for passive transport and facilitated diffusion show that Jmax (rate of uptake) is dependent on the external concentration.
Transporter Affinity
- Transporter affinity for solutes is given by the Km (Michaelis constant).
- A lower Km indicates a higher affinity for the solute.
Glucose Transporters (GLUT)
- A family of related glucose transporters with different locations and functions.
- GLUT1: ubiquitous, low Km (high affinity), mediates constitutive glucose uptake in many tissues.
- GLUT2: liver, pancreatic β-cells, high Km (low affinity), large Jmax (high capacity), transports glucose into hepatocytes and β-cells.
- GLUT3: neurons, low Km (high affinity).
- GLUT4: muscle, adipocytes, Km similar to fed-state blood glucose concentration, regulated by insulin.
Insulin-Stimulated Glucose Uptake
- Insulin stimulates glucose uptake in muscle and adipose tissue by increasing the amount of GLUT4 in the plasma membrane.
- Insulin triggers the movement of vesicles containing GLUT4 to the plasma membrane, increasing the uptake of glucose into the cell.
Gated Ion Channels
- Ion channels that allow facilitated diffusion, selective for different ions, open or close in response to a stimulus.
- Examples include ligand-gated channels (e.g., acetylcholine receptor) and voltage-gated channels (e.g., Na+ and K+ channels in axons involved in nerve transmission).
Active Transport
- Solutes move against a concentration gradient, requiring energy from ATP hydrolysis.
- Primary active transport: ATP hydrolysis directly causes the movement of solutes (uniport).
- Example: Na+/K+ pump (Na+/K+ ATPase) in plasma membrane.
Na+/K+ Pump (Na+/K+ ATPase)
- A tetramer (α2β2) that pumps Na+ out of the cell and K+ into the cell, establishing an electrochemical gradient.
- The pump consists of an open cytoplasmic access, phosphorylation from ATP at the cytoplasmic site, conformational change, and hydrolysis of the phosphate group.
Co-Transport Systems
- A pre-established gradient is used to drive transport of solutes across the membrane against a gradient.
- ATP hydrolysis is used to establish the primary gradient.
- Symport: transport of two solutes in the same direction.
- Antiport: transport of two solutes in opposite directions.
Na+/Glucose Cotransporter (SGLUT)
- A symport that uses the Na+ gradient established by the Na+/K+ pump to drive the uptake of glucose into cells.
- Secondary active transport.
Clinical Considerations
- Digitoxin: inhibits Na+/K+ pump, leading to increased [Na+] and [Ca2+] inside heart muscle, and increased contraction.
- Ouabain: inhibits Na+/K+ pump, leading to increased [Na+] and [Ca2+] inside heart muscle, and increased contraction.
- Cystic fibrosis: caused by mutations in the cystic fibrosis transmembrane conductance regulator protein (CFTR), leading to reduced chloride transport and thick mucus production.
- Cholera treatment: oral rehydration therapy includes high glucose concentration to drive Na+ uptake into cells via SGLUT, reducing electrolyte and fluid secretion.
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Description
Learn about the mechanisms of small-molecule transport across membranes, including passive diffusion, facilitated transport, and active transport. Understand the structure and function of the Na+/K+-ATPase membrane pump.