Lecture 3: Diffusion Flashcards
Biological membrane transport processes regulate
- The composition of body compartments
Transport processes can be used to explain
- Differences in composition between cytoplasm/extracellular fluid (ECF) and cytoplasm/cellular organelles
- How nutrients enter and waste products leave
- Regulation of substances in their absorption/reabsorption
Functions of membranes
- Act as barriers
- Oppose free movement of substances (hence have a resistance)
Movement of material through membranes is always
- Less than in free solution
Types of transport THROUGH membranes
- Simple/passive/non-mediated
- Mediated
Passive/non-mediated processes
- Simple diffusion (no energy required)
- Osmosis (no energy required)
Mediated transport processes
- Facilitated diffusion (no energy required)
- Exchange diffusion (no energy required)
- Active transport/primary active transport
- Secondary active transport
Active transport/primary active transport
- Energy required at site of transport
Secondary active transport
- Energy required but not at site of transport
Examples of transport ACROSS membrane
- Endocytosis (receptor mediated)
- Exocytosis (SNARE mediated)
- Pinocytosis
- Phagocytosis
Pinocytosis
- Cell drinking
- Engulfment of solute
- Transport across membranes, but not through
Pinocytosis found in
- Kidney tubular cells
- Intestinal epithelia
- WBC
- Kupffer cells in liver
- Some malignant cells
Characteristics of pinocytosis
- Variety of substances can induce formation of vesicles
- An active process requiring energy for vesicle formation
Substances that can induce pinocytosis
- Proteins
- Viruses
- Amino acids
- Ions
Substances than cannot induce pinocytosis
- Carbohydrates
- Nucleic acids
Active process requiring energy for vesicle formation during pinocytosis
- Selective aspect is the binding of inducer molecules to cell surface
- Coating protein on cytoplasmic side of membrane
Pinocytosis may involve
- Regions of membrane containing coated pits
- High levels of clathrin protein
Endocytosis can occur in
- Membrane areas lacking coated pits
- Sometimes called receptor mediated endocytosis
Other roles of pinocytosis
- Transport of proteins into embryonic cells
- Transport of B12 (intrinsic factor complex in ileum)
- Transport of some ions
- Absorption of antibodies in infants’ intestine (colostrum from breast milk after birth)
Phagocytosis
- Another example of endocytosis
- Involves particulate/solid matter
Exocytosis (secretion) example
- Nurotransmitter release (eurosecretion) of hypothalamic releasing hormones
- Ca2+ ions are important trigger molecules
SNARE proteins
- SNAP receptor protein
- Found on vesicular (v-SNAREs) and on target (t-SNAREs) membranes
- Calcium interacts with one of the v-SNAREs to permit vesicle to bind to cell membrane
Diffusion definition
- The net movement of a solute from a region of high concentration to an area of low concentration (concentration gradient)
Diffusion occurs due to
- Random thermal motion of atoms and molecules (i.e. Brownian movement)
Diffusion equilibrium is achieved and can be defined as
- A condition in which there is no net movement
- The unidirectional movements are equal
Restrictions to diffusion
- Effective only over short distances
- Mammals require huge efficient cardiovascular/renal/nervous systems to overcome severe limitations imposed by the laws of diffusion
Time for equilibration over distances
- Few microns = seconds
- Few centimeters = days
Diffusion imposes constraints on size of cells because
- Cellular metabolic rate in large cells would be limited by diffusion of nutrients from plasma membrane to interior of cell
Size of mammalian cells with high metabolic rates
- Less than 20 μm in diameter
No metabolically active cell in the body is
- More than 20 μm on average from a capillary bed
The capillary surface of 1gm of brain tissue is
- About 250 cm2
Factors influencing the magnitude of the permeability coefficient (Pm)
- Membrane partition coefficient, bp
- Membrane diffusion coefficient, Dm
- Membrane thickness, Xm
Membrane partition coefficient, bp
- Main determinant of Pm
Membrane diffusion coefficient, Dm
- Vary by less than a factor of 10
Membrane thickness, Xm
- Constant for any given cell
For any given membrane the range in Pm for a variety of molecules can be up to
- Eight orders of magnitude
Other factors that affect Pm
- H bonding between a solute and water
- Addition of one -OH group to solute
- Addition of one -CH3 group to solute
- Halogenation
H bonding between a solute and water
- Lowers bp and Pm
- i.e. reduces solutes lipid solubility
Addition of one -OH group to solute
- Can reduce Pm by 100 fold
Addition of one -CH3 group to solute
- Can increase Pm by up to 10 fold
Halogenation
- Increases Pm
Examples of molecules that can permeate biological membranes
- Gases
- Uncharged particles
- Weak acids or bases in unionized form
- Polar and lipid soluble molecules
- (Rate of transport is directly proportional to the concentration gradient)
Rates of absorption of drugs from GI tract can be enhanced by
- Adding methyl groups
- Halogenation of the drug
Rates of absorption of drugs from GI tract can be slowed by
- Substituting OH groups for the H atoms
All small molecules are
- Highly permeable
The dominant force controlling permeation
- Molecular size
- Where Pm alpha 1/molecular volume
- (only for molecules smaller than glucose)
Glucose has a radius of 0.42
- 0.42 nm
- Pores are passive channels and are ubiquitous
Pores provide
- Diffusional pathways
Small molecules are carried via
- Mediated type of transport
Small molecules like water can squeeze between
- Hydrocarbon tails in lipid bilayer.
Osmosis (special case of diffusion)
- Net movement of water from a dilute solution (higher water potential) to concentrated solution (lower water potential) across a semi-permeable membrane
Osmolality
- Measure of the number of particles in a solution
- Not their size or weight
Osmolality can be determined by
- Using a property of the solution that depends on the solute concentration (colligative properties of the solution)
Colligative properties of the solution affecting osmolality include changes in
- Boiling/freezing point
- Vapor pressure
- Absolute osmotic pressure
Osmotic pressure is defined as
- The hydrostatic pressure required to stop water movement across a semipermeable membrane
- Occurring because of an osmotic gradient (osmotic flow)
While the solute distribution in fluid compartments is specific, their total concentration
- Is similar
- Therefore, no great osmotic difference exists between the compartments
Diffusion occurs between compartments due to
- Solute imbalances
- Determined by properties related to the solute particle and the barrier across which it is diffusing
Functions of a membrane
- Structural (attach cell to ECM and adjacent cells)
- Detect chemical signals
- Signal transduction
- Act as barriers
- Compartmentalization
Membrane transport processes regulate
- Composition of body compartments
- (Intra- vs Extracellular)
- (Cytosolic vs intra-organelle)
Transport ACROSS not through a membrane
- Endocytosis (entry/engulfment)
- Exocytosis (exit or secretion)
Endocytosis (entry/engulfment)
- Phago- (solid)
- Pino- (liquid)
- Energy consumed
- Can involve activation of inducer molecules that trigger the process (hence, receptor-mediated endocytosis)
Exocytosis (exit or secretion)
- Requires interaction of SNARE proteins
- Calcium also needed
Diffusion definition
- The net movement of a solute from a region of high concentration to a region of low concentration
- Movement is said to occur downhill
- Random elastic collisions are the motive force
Diffusion equilibrium characteristics
- Solute concentration are equal throughout the solution
- Does not require outside energy in order to be maintained
- No NET movement of particles within solution
Diffusion limitations
- Very efficient over short distances (µm)
- Cell Size
- Distance from supply routes
- Evolution of delivery systems to keep diffusion distances short
Influences on Pm
- Partition coefficient, bp
- Membrane Diffusion coefficient, Dm
- Membrane thickness, Xm
Influences that lower Pm
- H-bonding between solute and solvent
- Hydroxylation
Influences that increase Pm
- Methylation
- Halogenation
Osmosis (special case of diffusion of water)
- Same principles apply as for solute diffusion
- Movement FROM a region of high [H2O] TO a region of low [H2O]
Concentration of pure water
- 55.5 M
- Therefore any solution will have a lower [H2O] than pure water
Osmolarity v Osmolality
- Determined simply by total number of particles in a solution
Osmolarity & Osmolality
- Effect on water movement can be “temporary”
- Tonicity: determined by the number of impermeant particles in a solution
- Tonicity has permanent effect on water distribution
Body compartments
- 66% body weight is water
- 55% in women; ~75% in newborn
- 66% intracellular (ICF)
- 33% extracellular (ECF)
- 75% ECF water is outside blood vessels (interstitial)
- 25% ECF water is inside blood vessels (plasma)
Total intra and extracellular ionic concentration is similar, but
- Many specific ionic concentration differences exist between the compartments
Osmosis of water follows
- Same principles as diffusion of solutes
Most body water is
- Intracellular
Total ionic concentration inside cells is
- Similar to that outside cells
