Membrane Epithelial membranes Ch 1: Membrane Dynamics – vs. 2 Meanings! Cell membranes and Membranes around organelles Cell membrane structures and functions
Membranes form fluid body compartments
Membranes as barriers and gatekeepers
How products move across membranes
i.e., methods of transport
Distribution of water and solutes in cells & the body
Chemical and electrical imbalances
Membrane permeability and changes
Thickness ~ 8nm Membrane Structure: Protein to Cell Membrane Structure: Fluid Mosaic Model Lipid Ratio varies from cell type to cell type
PLs Ratio for cells with high metabolic activity? Cholesterol Proteins: peripheral (associated) or integral
Membrane Other Phospholipid Behaviors in
Proteins H2O:
Integral Phospholipid bilayer (Membrane- Associated spanning or (peripheral or Micelle intrinsic ) extrinsic) Role in digestion and absorption of fats in GI Can span membrane Loosely bound to tract several times membrane
Either move around or Liposome are kept in place by Enzymes and Larger, bilayer, hollow cytoskeleton proteins structural proteins center with aqueous core Clinical relevance? Allows for cell polarity
11 Passive Transport Movement across Membrane = Diffusion (Def?) – 3 types:
1. simple diffusion Membrane permeability varies for 2. osmosis 3. facilitated diffusion (= mediated transport) different molecules & cell types Active Transport Two movement categories: depends on?? Always protein-mediated – 3 types: Passive and co -transport vesicular transport Active receptor mediated transport
Cytoskeleton Proteins Membrane Spanning Protein anchor membrane proteins
Fig 5-5
Diffusion Process (Passive) Distance – Time Relationship •Uses energy of concentration Time for diffusion to progress to given gradient •Net movement until state of distance ~ to distance squared equilibrium reached (no more conc. gradient) diffusion over 100 m takes 5 sec. •Direct correlation to temperature (why?) (why?) Fig 5-5 •Indirect correlation to molecule diffusion over 200 m takes ?? size •Slower with increasing distance diffusion over 400 m takes ?? •Lipophilic molecules can difuse through the phospholipid bilayer through the phospholipid bilayer diffusion over 800 m takes ??
Diffusion effective only over short distances!
22 Membrane Proteins
Fick’s law of Diffusion (p 135)
surface area x conc. gradient rate of = diffusion membrane resistance x membrane thickness Fig 5-7
depends on size and lipid-solubility of molecule and composition of lipid bilayer
Transporters Protein-Mediated Transport Cell Membrane Regulates Exchange with Environment More selective Many molecules use transporters to Active or Passive cross cell membrane. Why? Examples ? Membrane Proteins Structural Two categories of transporter proteins Enzymes 1. Channel proteins (rapid but not as Receptors selective – for small molecules only, e.g., Transporters (allows Specificity, water and ions) Competition, Saturation p 145) 2. Carrier proteins (slower but very Channel selective – also works for large Gated molecules)
Open Channels vs. Gated 1. Channel Proteins 1. Channel Proteins Channels Channels Gates closed most of the time For small molecules such as ?? = pores Chemically gated channels (controlled by messenger molecule Have gates, but or ligand) Aquaporin; plus > 100 gates are open ion channels most of the time. Voltage gated channels (controlled by electrical state of cell) Also referred to as Selectivity based on “leak channels”. Mechanically gated size & charge of channels (controlled by physical state of cell: temp.; stretching of cell molecule membrane etc.)
All have gate region
Open
Gated
33 Cotransport 2. Carrier Proteins Symport Never form direct connection Molecules are carried between ECF and ICF – 2 in same direction gates! Examples: Glucose + Bind molecules and change and Na conformation Antiport
Used for small organic Molecules are carried molecules (such as?) in opposite direction + + Examples: Na /K Ions may use channels or pump carriers
Rel. slow (1,000 to 1 Mio / sec)
Facilitated Diffusion (as a Active Transport form of carrier mediated transport)
Some characteristics same as simple Movement from low diffusion conc. to high conc. ATP needed
but also: Creates state of dis equilibrium specificity o competition 1 (direct) active transport saturation ATPases or “pumps ” (uniport and antiport)– examples? Figs 5-18/20 o 2 (indirect) active transport Symport and antiport
1o (Direct) Active Transport Mechanism of the Na +/K +- ATPase ATP energy directly fuels transport
+ + start Most important example: Na /K pump = sodium-potassium ATPase (uses up to 30% of cell’s ATP)
Fig 5-16
Establishes Na+ ECF: high [Na +], low [K +] conc. gradient ⇒⇒⇒ ICF: high [K +], low [Na +] Epot. can be harnessed for other cell functions Fig 5-17
44 2o (Indirect) Active Transport Body Fluid Compartments
Indirect ATP use: uses Epot. stored in concentration gradient IC fluid EC fluid (of Na + and K +)
Coupling of Ekin of one molecule with movement Exchange of another molecule much more selective; Interstitial fluid plasma + Example: Na / Glucose Why ? symporter Relatively free exchange
other examples
2 mechanisms for Glucose transport Fig 5-13
Body Fluid Compartments: Competition and Saturation Critical Thinking Question Fig 20 Fig 5-18 Glucose and fructose use same transport protein ECF ICF What properties should a molecule have to be used as marker for one of the fluid compartments?
Do total H 2O; total EC and plasma. Then, how do you figure out ICF and interstitial fluid? Saturation of carrier mediated transport:
Table 5-4 Vesicular Transport
Movement of macromolecules across cell membrane: 1. Phagocytosis (specialized cells only)
2. Endocytosis Pinocytosis Receptor mediated endocytosis (Caveolae) Potocytosis
3. Exocytosis
55 2. Endocytosis 1. Phagocytosis Requires energy Requires energy No pseudopodia - Membrane surface indents
Cell engulfs particle into vesicle via Smaller vesicles pseudopodia formation Nonselective: Pinocytosis for fluids & dissolved E.g.: some WBCs engulf bacteria substances
Vesicles formed are much larger than those Selective: Receptor Mediated Endocytosis via clathrin-coated formed by endocytosis pits - Example: LDL cholesterol and Familial Hypercholesterolemia Phagosome fuses with lysosomes ⇒ ? (see ⇒⇒ Podocytosis via caveolae Fig 5-24 Fig. 5-23)
Receptor Mediated Endocytosis and Membrane Recycling 3. Exocytosis Intracellular vesicle fuses with membrane →→→ Requires energy (ATP) and Ca 2+ Examples: large lipophobic molecule secretion; receptor insertion; waste removal
Fig 5-28
Movement through Epithelia: Transepithelial Transport of Glucose Transepithelial transport 1. Na +/Glucose symporter only found Uses combination of active and passive transport on apical side apical 2. Na +/K +-ATPase only Molecule must found on basolateral cross two side phospholipid bilayers 3. Facilitated diffusion basolateral
Apical and basolateral cell membranes have different proteins : Na +- glucose transporter on apical membrane Na +/K +-ATPase only on basolateral membrane Fig 5-26 Concept check: Apply Ouabain to either side of cell, what happens?
66 Distribution of Solutes in Transcytosis Body Endocytosis →→→ vesicular transport →→→ exocytosis Depends on selective permeability of cell Moves large proteins intact membrane transport mechanisms available Examples: Water is in osmotic equilibrium (free Absorption of maternal movement across membranes) antibodies from breast milk Ions and most solutes are in chemical disequilibrium (e.g., Na-K ATPase Movement of proteins Pump) across capillary endothelium Electrical disequilibrium between ECF and ICF Fig 5-33
Distribution of Solutes in Body Fluid Compartments Compare to Fig. 5-29 Compare to Fig 5-33 Osmosis Movement of water down its concentration gradient. Opposes movement Osmotic of water pressure across membrane
Water moves freely in body until osmotic equilibrium is reached
Convert Molarity to Molarity vs. Osmolarity Osmolarity
In chemistry: In Physiology Osmolarity = # of particles / L of solution
Mole / L Important is not # of 1 M glucose = 1 OsM glucose molecules / L but Avogadro’s # / L 1 M NaCl = 2 OsM NaCl # of particles / L: osmol/L or OsM 1 M MgCl 2 = 3 OsM MgCl 2 Why? Osmolarity of human body ~ 300 mOsM Osmolarity takes into account
dissociation (solubility) of molecules Compare isosmotic, hyperosmotic, hyposmotic (p in solution 156) Osmolality = OsM/Kg of sol’n
77 Tonicity Penetrating vs. Nonpenetrating Solutes
Physiological term describing how Penetrating solute: can enter cell cell volume changes if cell placed in (glucose, urea) the solution Nonpenetrating solutes: cannot enter Always comparative. Has no units. cell (sucrose, NaCl*)
Isotonic sol’n = No change in cell Determine relative conc. of Hypertonic sol’n = cell shrinks nonpenetrating solutes in solution Hypotonic = cell expands and in cell to determine tonicity. Water will move to dilute nonpenetrating solutes Depends not just on osmolarity but Penetrating solutes will distribute to equilibrium on nature of solutes and permeability of membrane Fig 5-30
Osmolarity and Tonicity IV Fluid Therapy Comparison 2 different purposes:
Get fluid into dehydrated cells or
Keep fluid in extra-cellular compartment
A is isosmotic to B A is hypotonic to B
Compare to Fig 5-35
Ch 5: Membrane Dynamics, Part 2 Electrical Disequilibrium and
Resting Membrane Potential Cell membrane structures and functions (pp.156-163) will be covered at the Membranes form fluid body compartments beginning of Ch 8 Membranes as barriers and gatekeepers How products move across membranes
i.e., methods of transport
Vesicular
Transepithelial
Osmosis
Distribution of water and solutes in cells & the body
Chemical and electrical imbalances
Resting Membrane Potential
Membrane permeability and changes
88 Membrane Dynamics, Part 1 Review Vesicular Transport
Law of Mass Balance Movement of macromolecules across
Ins = outs cell membrane: 1. Phagocytosis (specialized cells Diffusion only) Too slow for many processes Facilitated Diffusion 2. Endocytosis Pinocytosis Carrier proteins Receptor mediated endocytosis Protein-mediated (Caveolae) Potocytosis Transport Very selective 3. Exocytosis Active Transport uses ATP + + Na -K ATPase pump
2. Endocytosis 1. Phagocytosis
Requires energy Requires energy Cell engulfs particle into vesicle via pseudopod No pseudopodia - Membrane surface formation indents
E.g.: some WBCs engulf Smaller vesicles bacteria
Vesicles formed are much Nonselective: Pinocytosis for fluids & larger than those formed by dissolved substances endocytosis Selective: Phagosome fuses with Receptor Mediated Endocytosis via clathrin- Fig 5-24 lysosomes ⇒⇒⇒ ? (see Fig. 5-23 ) coated pits - Example: LDL cholesterol and Familial Hypercholesterolemia
Potocytosis via caveolae
Receptor Mediated Endocytosis and 3. Exocytosis Membrane Recycling •Intracellular vesicle fuses with membrane →→→ •Requires energy (ATP) and Ca 2+ •Uses: •large lipophobic molecule secretion; • receptor insertion; •waste removal
Fig 5-28
99 Movement through Epithelia: Transepithelial Transport of Glucose Transepithelial Transport 1. Na +/Glucose symporter only Uses combination of active and passive transport found on apical side
2. Na +/K +-ATPase Molecule must only found on cross two basolateral side phospholipid bilayers 3. Facilitated diffusion
Apical and basolateral cell membranes have different proteins : Na +- glucose transporter on apical membrane Na +/K +-ATPase only on basolateral membrane Fig 5-26
Transcytosis Distribution of Solutes in Body Endocytosis →→→ vesicular transport →→→ exocytosis Depends on Moves large proteins intact selective permeability of cell membrane Examples: transport mechanisms available Absorption of maternal antibodies from Water is in osmotic equilibrium (free breast milk movement across membranes) Ions and most solutes are in chemical Movement of proteins disequilibrium (e.g., Na-K ATPase across capillary Pump) endothelium Electrical disequilibrium between ECF Fig 5-33 and ICF
Distribution of Solutes in Body Fluid Compartments Compare to Fig. 5-29 Compare to Fig 5-33 Osmosis Movement of water down its concentration gradient. Opposes Osmotic movement of water pressure across membrane
Water moves freely in body until osmotic equilibrium is reached
1010 Convert Molarity to Molarity vs. Osmolarity Osmolarity
In chemistry: In Physiology Osmolarity = # of particles / L of solution Mole / L Important is not # of
Avogadro’s # / L molecules / L but 1 M glucose = 1 OsM glucose
# of particles / L: osmol/L 1 M NaCl = 2 OsM NaCl or OsM 1 M MgCl 2 = 3 OsM MgCl 2 Why? Osmolarity takes into account Osmolarity of human body ~ 300 mOsM dissociation (solubility) of molecules in solution Compare isosmotic, hyperosmotic, Osmolality = OsM/Kg of sol’n hyposmotic (p 156)
Tonicity Penetrating vs. Nonpenetrating Solutes
Penetrating solute: can enter cell Physiological term describing (glucose, urea) how cell volume changes if cell Nonpenetrating solutes: cannot enter placed in the solution cell (sucrose, NaCl*) Always comparative. Has no Determine relative conc. of units. nonpenetrating solutes in solution Isotonic sol’n = No change in cell and in cell to determine tonicity. Hypertonic sol’n = cell shrinks Water will move to dilute nonpenetrating solutes Penetrating solutes will distribute to equilibrium Hypotonic = cell expands
Depends not just on osmolarity but on nature of solutes and Fig 5-30 permeability of membrane
Osmolarity and Tonicity IV Fluid Therapy Comparison
2 different purposes:
Get fluid into dehydrated cells or
Keep fluid in extra-cellular compartment
A is isosmotic to B A is hypotonic to B
Compare to Fig 5-35
1111 Electrical Disequilibrium and Resting Membrane Potential (pp.156-163) will be covered at the beginning of Ch 8
Which of the following is a way for solutes in a Which of the following defines the aqueous solution to move from an area of high term specificity? solute concentration to an area of low solute concentration? A. movement of molecules by the use of vesicles
B. the energy required to move molecules
A. Facilitated diffusion C. a group of carrier proteins operating at their maximum rate B. Osmosis D. carrier transport of a group of closely C. Active transport related molecules D. A and B E. none of these E. None of these
Water will always move from ______situations to ______Which of the following pairs of molecular situations. characteristics favors diffusion through the cell membrane?
A. Hyperosmotic, hyposmotic A. Large, polar
B. Hyposmotic, hyperosmotic B. Large, non-polar
C. Hyposmotic, isosmotic C. Small, polar
D. Hyperosmotic, isosmotic D. Small, non-polar
1212 Which of the following is a way for solutes in a aqueous solution to move from an area of high solute concentration to an area of low solute concentration?
A. Facilitated diffusion
B. Osmosis
C. Active transport
D. A and B
E. None of these
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