Transport in Biological Systems PDF

Transport in biological systems - All biological systems are composed of cells. Cells are surrounded by a selective plasma membrane. The plasma membrane regulates the exchange of different substances between the cell and interstitial fluid. Substances (oxygen, carbon dioxi...

Transport in biological systems - All biological systems are composed of cells. Cells are surrounded by a selective plasma membrane. The plasma membrane regulates the exchange of different substances between the cell and interstitial fluid. Substances (oxygen, carbon dioxide, ions, glucose, amino acids, fatty acids, products of metabolism, microelements and vitamins) have different size, shape and molecular weight - Types of transport o Passive transport ▪ Simple diffusion ▪ Facilitated diffusion ▪ Osmosis ▪ Filtration o Active transport (primary active transport) o Coupled transport (secondary active transport) o Endocytosis Passive transport – simple diffusion - Diffusion is a random process of movement of any molecules (solid, liquid, or gas) from one location to another through the random thermal motion - The amount of substance crossing biological membrane in a time is called flux - The net flux between two compartments is always from an area of higher concentration of any substance to an area of lower concentration - Diffusion of a molecule across biological membrane depends upon molecular weight of the substance - Thus, heavier molecules diffuse slower than lighter molecules Ficks Law of Diffusion (Adolf Fick, 1855) - RT – the rate of transport (flux) - (C1-C2) - the concentration gradient across the membrane - S = surface area of diffusion - D = diffusion coefficient - ∆x = distance of diffusion Diffusion coefficient - The stokes-Einstein equation: D=KBT/6πηr = E/6πηr o D = diffusion coefficient o KB = Boltzmann’s constant o T = absolute temperature o r = molecular radius o η = viscosity of the medium - ↑D: ↑E, ↑T, ↓η,↓r - ↓D: ↓E, ↓T, ↑η, ↑r RT = DS △C/△X - ↑RT: ↑D, ↑E, ↑T, ↓η,↓r - ↓RT: ↓D, ↓E, ↓T, ↑η, ↑r Molecules progressively spread in space - For diffusion in one dimension: d1-D √2Dt - For diffusion in two dimensions: d2-D √4Dt - For diffusion in three dimensions: d3-D √6Dt o d = distance of diffusion o D = diffusion coefficient o t = time of diffusion The distance of diffusion is proportional to the square root of time - Diffusion is effective over short distances – nanometers and micrometers o t = d2/6D - Distance change –2 times ---> Diffusion change –4 times - Distance change –10 times ---> Diffusion change –100 times Diffusion constrains in cell physiology  - Diffusion coefficient for small molecules is about 5*10-6 cm2/s - If a distance of diffusion is 10um (0.001cm) o Diffusion time: t = (0.001)2/6D = 0.03sec - If a distance of diffusion is 100um (0.01cm) o Diffusion time: t = (0.01)2/6D = 3.3sec - If a distance of diffusion is 10,000um (1cm) o Diffusion time: t = (1)2/6D = 9.3hrs The typical Time scale of water molecules collisions - d – typical distance between water molecules: 0.2nm - v – typical velocity of a water molecule: 500m/s - v=d/t - t=d/v - t=0.4*10-12 s (about half of a picosecond) Permeability - Substances are also characterized by the permeability coefficient P (cm/s) o P=v (velocity) o P=KD/△x ▪ P = permeability coefficient (cm/s) ▪ K = dimensionless partition coefficient – is the oil/water solubility of a substance ▪ D = diffusion coefficient (cm2/s) ▪ △x = distance of diffusion - Permeability is the speed of diffusion across the unit area of the membrane - T=PS (C1-C2) / RT= PS (C1-C2) - Oxygen, carbon dioxide, water, and anesthetic gases have very high permeability P = KB T/6πηr△x = velocity ↓P: ↑ molecular weight, ↑ size, ↑ polarity, ↑ ionic state, ↑ hydration ↑P: ↓ molecular weight, ↓ size, ↓polarity, ↓ ionic state, ↓ hydration THUS: ↑T, ↑S, ↑△C, ↓η,↓r, ↓△x, ↓MW, ↓P, ↓ionic state, ↓hydration: ↑RT ↓ T, ↓S, ↓△C, ↑η, ↑r, ↑△x, ↑MW, ↑P, ↑ionic state, ↑hydration: ↓RT Some biological Diffusion coefficients (cm2/s) - Small molecules in water = 10-5 - Protein in water = 10-6 - Phospholipid in membrane = 10-8 - Protein in membrane = 10-9 Permeability and molecular size - The bilayer is more permeable to smaller molecules than the large molecules - Heavier molecules diffuse slower than lighter molecules - Transport of small molecules is also restricted - Thus, water molecules pass the phospholipid bilayer 10,000 lower than in bulk Permeability and polarity - The bilayer is more permeable to nonpolar molecules than polar molecules - Propanol/glycerol permeability ratio 103: 1 Permeability and ions  - Bilayer is highly impermeable to ions - Ions associate with water molecules, forming hydration shell - Hydration shell dramatically restricts ion transport across the membrane - O2/OH - permeability ratio 109: 1 Simple diffusion through the membrane and selective channels - Nonpolar (non-ionized) substances (oxygen, carbon dioxide, fatty acids, lipid- soluble hormones) diffuse directly across phospholipid bilayer of biological membranes - Polar (ionized) substances -must pass biological membranes through the selective ion channels, which are typically formed by integral proteins. Most channels are characterized by similar designs. Proteins are configured to create a transmembrane water-filled channel. Water filled pores allow ions to diffuse across the membrane. Simple diffusion and channels - Concept of channels was introduced in 1950s - Channels are integral proteins was established in 1970s - In humans > 400 genes encode channel proteins - Channels are characterized by evolutionary relationship Membrane channels - Channels are formed by integral proteins 1. Selective Ion channels (H+, Na+, K+, Ca2+, Cl-, and HCO3-) 2. Porins (high molecular weight solutes) 3. Aquaporins (water) Three types of selective ion channels 1. Voltage-gated (voltage operated) channels 2. Ligand-sensitive (ligand-operating; chemosensitive) channels 3. Mechanosensitive channel Selective ion channels - Remarkably selective - Negative charge at the channel entrance - Hydrophilic ion channels are formed by integral proteins - Allow passage only of one type of iron (H+, Na+, K+, Ca2+, Cl-, and HCO3-) - Difference in charge and size of ions is small (Na+ = 0.095nm; K+ = 0.133nm)  - Narrow region acts as selectivity filter and contains carboxyl and carbonyl groups - Selective filter for K+ = 0.3nm - Transport rate: 106-108 ions/sec Pores - Less specific - Formed by transmembrane proteins – porins - Often between the similar cells (gap junctions) - Form β-barrel - (water-filled pore) - Larger than ionic channels (1.2nm) - Allow passage of hydrophilic solutes: anions, cations, ATP, cAMP, and IP3 - Size of a pore limits size of a solute (