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Note Set 9 1 November 14, 2000 TRANSPORT ACROSS MEMBRANES Cell or organelle is not wholly closed or wholly open to surroundings Interior must be protected from certain toxic cmpds, metabolites must be taken in, products are sometimes removed, waste products need to be removed, thousands of substances involved Three categories: Passive Facilitated Active The Thermodynamics of Transport G = RT ln C2 C1 Free energy change, ∆ G, for transporting 1 mol of substance from region where concentration is C1 to region where concentration is C2 If C2 < C1 then ∆ G is negative Favorable As more is transferred (between two finite compartments) C1 decreases and C2 increases until C2 =C1 Then ∆ G = 0 and system is at equilibrium Unless other factors involved, this is ultimate state, will eventually be same concentration on each side "Kinetic" way to see this result: 1 Note Set 9 2 November 14, 2000 If molecules wandering into membrane at random, number entering from each side is proportional to concentration on that side When concentrations are equal, rates of transport/movement in both directions is the same, and there is no net transport in either direction The rate of transport, J (moles/cm2/sec, is proportional to the difference between C2 and C1 J = -KD1 (C2 - C1)/l C1 and C2 in mol/cm3 l = thickness of membrane (cm) D1 is the diffusion coeeficient (cm2/sec) K is the partition coefficient, a ratio of the solubilities in lipid and water Symplified by use of a term P (cm/sec), permeability constant so that ( P = KD1/l) J = -P(C1 - C2) see Table 10.6 Three "other factors" can circumvent this equalization: 1. Substance is bound by macromolecules confined to one side of membrane Not "free", so doesn't count in equation O2 in red blood cells bound to Hb; total O2 in cell much higher than in plasma "Free" O2 in erythrocyte and plasma is the same 2. Membrane electrical potential affects distribution of ions If inside negative w/ respect to outside, cations will be drawn inside, and anions want to leave Affects ∆ G 2 Note Set 9 G = RT ln 3 November 14, 2000 C2 +ZF C1 F = Faraday constant (96.5 kJ mol-1 V-1) ∆ψ = membrane potential in volts Z = charge on ion being considered If ∆ψ is negative going from ouside to in, and Z is positive, then ZF makes a negative contribution to ∆ G and transport in of cations is favored In this case, equilibrium state will not correspond to equal concentration of ions on both sides of membrane But energy must be used to maintain membrane potential This is a special case of active transport Can also be interpreted to mean if different ionic concentrations are maintained, potential. will develop accross membrane that can be used by a system not directly connected to the pump (usually ATPase-coupled) maintaining the potential If some other process is coupled to transport, its ∆ G must be included General case of active transport G = RT ln C2 + G' C1 For example, ATP hydrolysis could be the ∆ G' The two cases of active transport mean is that under the right circumstances, substances can be transported into or out of a cell or compartment against an unfavorable concentration difference 3 Note Set 9 4 November 14, 2000 For example, cells bring K+ in and move Na+ out against their concentration gradients Passive Transport: Diffusion This is molecular diffusion; random wandering of molecules through membrane due to Brownian motion of molecules in any fluid First equation applies (10.1) Problem with diffusion is that the lipid bilayer does not like ions and other hydrophilic substances so diffusion of these substances is very slow Exception is water: membranes are very permeable to water and no one knows exactly why Fortunate for life, however, as cells can exchange water very readily with surroundings Although leaves of desert plants have waxy substance to prevent water loss Membranes are also very permeasble to oxygen Facilitated Transport: Accelerated Diffusion Increases rate of diffusion: it's just a special form of diffusion Energy not required First equation still applies Pore-Facilitated Transport (Fig 10.20) A channel or ion pore is used For example, the uptake and release of chloride and bicarbonate in red blood cells: in capillaries, HCO3- taken up from erythrocyte release, and Cl- taken in to maintain anion balance in cell; process reversed in lungs; very selective, occurs on 1:1 basis 4 Note Set 9 5 November 14, 2000 A glucose pore called glucose transport protein is used by erthyrocyte to increase the diffusion of glucose 50,000-fold Some pores are gated: they open and close in response to control mechanisms Gap junctions between animal cells: they're open most of the time, but will close under some circumstances, like if the cell is damaged and Ca2+ increases Gated pores play a major role in the propagation of nerve impulses Ionophores Protein toxins that act by making hole in membrane and allowing indiscriminate movement of specific ions...kills cells. Made by bacteria to kill other bacteria, specific for bacterial membranes so they are used as antibiotics Can be another kind of pore Gramicidin A (Fig 10.22) produced by Bacillus brevis is a cation specific pore: screws up K+ gradient--2 molecules of gA needed to form pore, one from each membrane leaflet, together form helical pore 15-residue polypeptide that contains alternating L- and D-amino acids Carrier-Facilitated Transport Valinomycin (Fig 10.23) produced by Streptomyces : also screws up K+ gradient--out side is hydrophobic (lots of methyl groups), inside nicely accomodates K+ (Ns and Os) and carrier picks up an ion on one side of membrane, diffuses to other side and releases ion (does NOT "flip") Also has D- and L- amino acids Looks a little like a clathrate water cage Distinguishing Different Types of Diffusion (Fig 10.24) 5 Note Set 9 6 November 14, 2000 How can you tell the difference between diffusion and facilitated transport?? If it is facilitated it is saturable, by analogy to enzyme catalysis How can you tell the difference between a pore and a carrier? Pore does not depend on membrane fluidity for efficient function, carrier does. Fluidity influenced by various factors including lipid composition and temperature Active Transport: Transport Against a Concentration Gradient Ion pumps, cotransport, and transport by modification are all ways that a cell can transport a substance against a concentration gradient Ion pumps: Direct Coupling of ATP Hydrolysis to Transport Most cells spend 25% of ATP on active transport! Direct coupling of ATP hydrolysis to transport Sodium-potassium pump maintains sodium and potassium gradient in cell: called Na+ - K+ ATPase (Fig 10.25) Has binding sites for ouabain and digitalis (cardiotonic steroids) Fig 10.26 Na outside cell = 140mM, inside = 10mM and Na is transported out K out = 5mM, inside = 100mM and K is trans in Inside of memb. is more negative than ouside for Na+ out, membrane potential opposes flow: 140mM ∆ G = RT ln 10mM +1 x F x 0.07volts = 13.55 kJ/mol for 3 mol , need 40.65 kJ for K+ in: 6 Note Set 9 7 November 14, 2000 100mM ∆ G = RT ln 5mM +1 x F x (-0.07volts) = 0.97 kJ/mol for 2 mol , need 1.94 kJ For total process need 42.59 kJ -why is 1 ATP enuf?? isn't ∆ G = --30 kJ/mol?? -in most cells, [ATP] is much > than [ADP] and [Pi], so ∆ G of hydrolysis is more like 45-50 kJ/mol Pumps can run backwards and generate ATP Probably the major way that ATP is made in living organisms Cotransport Systems A substance to be transported against a concentration gradient "piggybacks" by moving with an ion that is going in the direction of a favorable gradient Sodium-glucose transport in the small intestine--transport of each molecule of glucose into cells is accompanied by the simultanious movement of one sodium ion in the same direction [Na] is lower in cell than outside...so energy is provided Many amino acids and sugars transported this way. Same direction = symport, opposite direction = antiport Transport by modification Transported substance is modified as soon as it gets into the cell, and thus is no longer free to leave, and no longer contributes to the equilibrium...therefore the substance can be accumulated against a concentration gradient Occurs in transport of many sugars (see Fig 10.27) 7 Note Set 9 8 November 14, 2000 Phosphorylation is common modification Glucose is phosphorylated to G-6-P, which is also the 1st step in the metabolic utilization of glucose Overview Transport very pervasive, continue to encounter during met. reg.,cells utilize all the kinds we discussed See Fig 10.28 8