Transport Across Membrane

1. Transport Across Membrane • Most of the substances that move across membranes are dissolved ions and small organic molecules- Solutes • Not macromolecules and fluids • Ions • Na+, K+, Ca2+, Cl-, H+ • Organic molecules • metabolites: sugars, amino acids, nucleotides • 20% of gene in E. coli- Transport

2. A membrane’s molecular organization results in selective permeability • A steady traffic of small molecules and ions moves across the plasma membrane in both directions. • For example, sugars, amino acids, and other nutrients enter a muscle cell and metabolic waste products leave. • The cell absorbs oxygen and expels carbon dioxide. • It also regulates concentrations of inorganic ions, like Na+, K+, Ca2+, and Cl-, by shuttling them across the membrane. • However, substances do not move across the barrier indiscriminately; membranes are selectively permeable.

3. Transport Across Membranes: Overcoming the Permeability Barrier  • Cells and Transport Processes • Simple Diffusion: Unassisted Movement Down the Gradient • Facilitated Diffusion: Protein-Mediated Movement Down the Gradient • Active Transport: Protein-Mediated Movement Up the Gradient • Examples of Active Transport

4. Cells and Transport Processes • Solutes cross membranes by simple diffusion, facilitated diffusion, and active transport • The movement of a solute across a membrane is determined by its concentration gradient or its electrochemical potential • The erythrocyte plasma membrane provides examples of transport mechanisms

5. Solutes cross membranes by simple diffusion, facilitated diffusion, and active transport • Simple Diffusion • O2, CO2, ethanol • Facilitated Diffusion (Transport protein required) • A gradient of concentration, charge, or both (glucose) • Active Transport (Transport protein required) • Na+, K+, Ca2+, Cl-, H+

6. The movement of a solute across a membrane is determined by its concentration gradient or its electrochemical potential • Concentration gradient • Electrochemical potential (the movement of ion) • Combined effect：concentration gradient and the charge gradient • Ion • Membrane potential (Vm) caused by active transport • Most cells have a negatively membrane potential. • Ion gradient can create an electrical voltage, or membrane potential • Across the membrane that makes one side of the membrane negative and the other side positive.

7. Permeability of a molecule through a membrane depends on the interaction of that molecule with the hydrophobic core of the membrane. • Hydrophobic molecules, like hydrocarbons, CO2, and O2, can dissolve in the lipid bilayer and cross easily. • Ions and polar molecules:hard to cross membrane. • This includes small molecules, like water, and larger critical molecules, like glucose and other sugars. • Ions, whether atoms or molecules, and their surrounding shell of water also have difficulties penetrating the hydrophobic region. • Proteins can assist and regulate the transport of ions and polar molecules.

8. Specific ions and polar molecules can cross the lipid bilayer by passing through transport proteins that span the membrane. • Some transport proteins have a hydrophilic channel that certain molecules or ions can use as a tunnel through the membrane. • Others bind to these molecules and carry their passengers across the membrane physically. • Each transport protein is specific as to the substances that it will translocate (move). • For example, the glucose transport protein in the liver will carry glucose from the blood to the cytoplasm, but not fructose, its structural isomer.

9. Transport Across Membranes: Overcoming the Permeability Barrier • Cells and Transport Processes • Simple Diffusion: Unassisted Movement Down the Gradient • Facilitated Diffusion: Protein-Mediated Movement Down the Gradient • Active Transport: Protein-Mediated Movement Up the Gradient • Examples of Active Transport 

10. Simple Diffusion: Unassisted Movement Down the Gradient • Diffusion always moves solutes toward equilibrium • Osmosis is the diffusion of water across a differentially permeable membrane • Simple diffusion is limited to small, nonpolar molecule • The rate of simple diffusion is directly proportional to the concentration gradient

11. Passive transport is diffusion across a membrane • Diffusion is the tendency of molecules of any substance to spread out in the available space • Diffusion is driven by the intrinsic kinetic energy (thermal motion or heat) of molecules. • Movements of individual molecules are random. • However, movement of a population of molecules may be directional.

12. The diffusion of a substance across a biological membrane is passive transport because it requires no energy from the cell to make it happen. • The concentration gradient represents potential energy and drives diffusion. • However, because membranes are selectively permeable, the interactions of the molecules with the membrane play a role in the diffusion rate. • Diffusion of molecules with limited permeability through the lipid bilayer may be assisted by transport proteins.

13. Osmosis is the diffusion of water across a differentially permeable membrane • Osmosis is the passive transport of water • Differences in the relative concentration of dissolved materials in two solutions can lead to the movement of ions from one to the other. • The solution with the higher concentration of solutes is hypertonic. • The solution with the lower concentration of solutes is hypotonic. • These are comparative terms. • Tap water is hypertonic compared to distilled water but hypotonic when compared to sea water. • Solutions with equal solute concentrations are isotonic.

14. Imagine that two sugar solutions differing in concentration are separated by a membrane that will allow water through, but not sugar. • The hypertonic solution has a lower water concentration than the hypotonic solution. • More of the water molecules in the hypertonic solution are bound up in hydration shells around the sugar molecules, leaving fewer unbound water molecules.

15. Cell survival depends on balancing water uptake and loss • An animal cell immersed in an isotonic environment no net movement of water across its plasma membrane. • Water flows across the membrane, but at the same rate in both directions. • The volume of the cell is stable.

16. For a cell living in an isotonic environment (for example, many marine invertebrates) osmosis is not a problem. • Similarly, the cells of most land animals are bathed in an extracellular fluid that is isotonic to the cells. • Organisms without rigid walls have osmotic problems in either a hypertonic or hypotonic environment and must have adaptations for osmoregulation to maintain their internal environment.

17. Simple Diffusion is Limited to Small, Nonpolar Molecules • Solute size • Lipid bilayers are more permeable to small molecules than to larger molecules • Water, O2, CO2 • Solute polarity • Permeable to nonpolar molecules and less permeable to polar molecules • Solute charge • Highly impermeable to ions that is very important to cells • Cell must maintain an ion gradient across its membrane in order to function

18. Transport Across Membranes: Overcoming the Permeability Barrier • Cells and Transport Processes • Simple Diffusion: Unassisted Movement Down the Gradient • Facilitated Diffusion: Protein-Mediated Movement Down the Gradient • Active Transport: Protein-Mediated Movement Up the Gradient • Examples of Active Transport 

19. Specific proteins facilitate passive transport of water and selected solutes: • Many polar molecules and ions that are normally impeded (阻擋) by the lipid bilayer of the membrane diffuse passively with the help of transport proteins that span the membrane. • The passive movement of molecules down its concentration gradient via a transportprotein is called facilitated diffusion.

20. Facilitated Diffusion: Protein-Mediated Movement Down the Gradient • Carrier proteins and channel proteins facilitate diffusion by different mechanism. • Carrier proteins alternate between two conformation states • Carrier proteins are analogous to enzymes in their specificity and kinetics • Carrier proteins transport either one or two solutes • The erythrocyte glucose transporter and anion exchange protein are examples of carrier proteins • Channel protein facilitate diffusion by forming hydrophilic transmembrane channel.

21. Carrier proteins and channel proteins facilitate diffusion by different mechanism • Two classes of proteins involved facilitate diffusion • Carrier Proteins (transporters or permeases ) • bind to the solute molecules • with change in the conformation of the protein • move the polar or charged molecules in or out of the cell through the hydrophobic membrane • Channel Proteins • form hydrophilic channel through the membrane • without any change in the conformation of the protein • molecular weight-up to 600 Da • ion channel • The transport rate: channel protein > carrier protein

22. Transport proteins have much in common with enzymes. • They may have specific binding sites for the solute. • Transport proteins can become saturated when they are translocating passengers as fast as they can. • Transport proteins can be inhibited by molecules that resemble the normal “substrate.”

23. The erythrocyte glucose transporter and anion exchange protein are examples of carrier proteins • The glucose transporter: A uniport carrier • The erythrocyte anion exchange protein: An antiport carrier

24. Channel Protein Facilitate Diffusion by Forming Hydrophilic Transmembrane Channel • Most ion channel are gated • Necessary for maintaining the proper salt balance in the cells • Lung cells：cystic fibrosis transmembrane conductance regulator (CFTR) • Maintain the proper Cl- concentration in lung

25. Channel Protein Facilitate Diffusion by Forming Hydrophilic Transmembrane Channel • Ion channels: Transmembrane proteins that allow rapid passage of specific ions • K+, Na+, Ca2+, Cl- • Most ion channel are gated- 三種因子控制gate的開與閉 • Voltage-gated channels- membrane potential • Ligand-gated channels- binding of specific substances • Mechanosensitive channels- mechanical forces • Porins: Transmembrane proteins that allow rapid passage of various solutes • in outer membrane of mitochondria, chloroplasts and bacteria • Aquaporins Transmembrane channel that allow rapid passage of water • erythrocytes, kidney (reabsorb water), central vacuolar

26. Transport Across Membranes: Overcoming the Permeability Barrier • Cells and Transport Processes • Simple Diffusion: Unassisted Movement Down the Gradient • Facilitated Diffusion: Protein-Mediated Movement Down the Gradient • Active Transport: Protein-Mediated Movement Up the Gradient • Examples of Active Transport 

27. Active Transport: Protein-Mediated Movement Up the Gradient • The Coupling of active transport to an energy source may be direct or indirect • Direct active transport depends on four types of transport ATPases • Indirect active transport is driven by ion gradients

28. Active transport is the pumping of solutes against their gradients • This active transport requires the cell to expend its own metabolic energy. • Three major functions: • uptake the essential nutrients from the environment • remove the substance (such as secretory products and waste) away from cell or organelle • maintain constant, nonequilibrium intracellular concentration of inorganic ion, K+, Na+, Ca2+ and H+

29. Active transport always moves solutes away from thermodynamic equilibrium • Require an input energy - ATP • Active transport is performed by specific proteins embedded in the membranes. • ATP supplies the energy for most active transport. • Often, ATP powers active transport by shifting a phosphate group from ATP (forming ADP) to the transport protein. • This may induce a conformational change in the transport protein that translocates the solute across the membrane.

30. The sodium-potassium pump actively maintains the gradient of sodium (Na+) and potassium ions (K+) across the membrane. • An important distinction between active transport and simple or facilitated diffusion: The direction of transport • Simple and facilitated diffusion: nondirectionality • Active transport: directionality- unidirectional (vectorial )process

31. In cotransport, a membrane protein couples the transport of two solutes • A single ATP-powered pump that transports one solute can indirectly drive the active transport of several other solutes through cotransport via a different protein. • As the solute that has been actively transported diffuses back passively through a transport protein, its movement can be coupled with the active transport of another substance against its concentration gradient.

32. Four Types of Transport ATPase • Most p-type ATPase are located in the plasma membrane • Maintaining an ion gradient across the membrane • V-type ATPase • Pump protons into organells, vacuoles, vesicles, lysosome, endosome, and Glgi • F-type ATPase found in bacteria, mitochondria an chloroplasts • Proton transport：use H+ gradient to drive ATP synthesis. • ABC-type ATPase • Antitumor drugs：plasma membrane • Multidrug resistance transport protein

33. ABC-Type ATPase • Four domains • Two are highly hydrophobic and are embedded in the membrane • ABC transporters are of considerable medical interest because some of them pump antibiotics or other drug out of the cells, thereby making the cell resistant to the drug. • Multidrug resistance (MDR) transport protein

34. Transport Across Membranes: Overcoming the Permeability Barrier • Cells and Transport Processes • Simple Diffusion: Unassisted Movement Down the Gradient • Facilitated Diffusion: Protein-Mediated Movement Down the Gradient • Active Transport: Protein-Mediated Movement Up the Gradient • Examples of Active Transport • The Energetics of Transport • On to Nerve Cells 

35. Examples of Active Transport • Direct active transport: The Na+/K+ pump maintains electrochemical ion gradients • Indirect active transport: Sodium symport drives the uptake of glucose • The bacteriorhodopsin proton pump uses light energy to transport protons

36. Exocytosis and endocytosis transport large molecules • Small molecules and water enter or leave the cell through the lipid bilayer or by transport proteins. • Large molecules, such as polysaccharides and proteins, cross the membrane via vesicles.