Biol2174 Cell Physiology in Health & Disease

Transcription

1 Biol2174 Cell Physiology in Health & Disease Lecture 4: Membrane Transport Proteins Kiaran Kirk Research School of Biology Learning objectives To understand: The need for membrane transport proteins in regulating the flux of physiologically relevant solutes across cell membranes The functional distinction between channels and transporters Passive and active transport The general characteristics of channels and transporters and the different properties that distinguish them from one another

2 Why we need membrane transport proteins Figure 11 2 Molecular Biology of the Cell ( Garland Science 2008) Why we need membrane transport proteins

3 Membrane transport proteins There are different types of membrane transport proteins. Physiologists have traditionally been assigned them into either one of two different classes: 'channels' on the one hand and 'transporters' or 'carriers' on the other. There are different types of channel, differing in their ion selectivity, their mode of activation (e.g. ligand gated, voltage gated) and in many other respects. Similarly there are different types of transporters. There is a great deal of inconsistency in the names that textbooks, biochemists and physiologists use for these different types of membrane protein. I use the term 'channel' for a protein which, when open provides an aqueous pathway that allows the diffusion of solutes from one side of the membrane to the other. I use the term 'transporter for a protein which has a solute binding site and which has to undergo a conformational change in order to allow the passage of the solute from one side of the membrane to the other. Figure 11 3b Molecular Biology of the Cell ( Garland Science 2008)

4 Figure Molecular Biology of the Cell ( Garland Science 2008) Figure Molecular Biology of the Cell ( Garland Science 2008)

5 Figure 11 3a Molecular Biology of the Cell ( Garland Science 2008) Figure 11 10a Molecular Biology of the Cell ( Garland Science 2008)

6 Uniporters and cotransporters Figure 11 8 Molecular Biology of the Cell ( Garland Science 2008) Passive vs active transport Figure 11 4a Molecular Biology of the Cell ( Garland Science 2008)

7 Active transport Secondary active transport Primary active transport Figure 11 7 Molecular Biology of the Cell ( Garland Science 2008) versus transporters rmal function General selectivity Stereoselectivity Thermodynamics Kinetics Substrate competition Trans effects Ion dependence Turnover number Membrane permeation of inorganic ions for the purpose of alteration/stabilisation of the membrane potential and/or bulk ion movements Discriminate between solutes on the basis of gross physical characteristics (size & charge) Transport solutes down (never up) the prevailing electrochemical gradient Saturate at high solute concentrations. though commonly not within physiological ion concentration ranges Don t usually show competition between different ions. Typically s 1 (basis for single channel recordings) Transport of wide range of solutes including inorganic ions and organic substrates May be highly selective, discriminating between solutes on the basis of subtle differences in chemical structure Often Mediate both passive and active transport (i.e. down and up) the prevailing electrochemical gradients Commonly show saturation kinetics within physiological substrate concentration ranges Competition between structurally similar solutes Commonly show trans stimulation (i.e. acceleration of the unidirectional flux of a solute in one direction by a high concentration of the solute on the opposite side of the membrane) Solute transport is commonly dependent on inorganic ions (typically, but not always, Na + ) Typically s 1

8 versus transporters rmal function General selectivity Stereoselectivity Thermodynamics Kinetics Substrate competition Trans effects Ion dependence Turnover number Membrane permeation of inorganic ions for the purpose of alteration/stabilisation of the membrane potential and/or bulk ion movements Discriminate between solutes on the basis of gross physical characteristics (size & charge) Transport solutes down (never up) the prevailing electrochemical gradient Saturate at high solute concentrations. though commonly not within physiological ion concentration ranges Don t usually show competition between different ions. Typically s 1 (basis for single channel recordings) Transport of wide range of solutes including inorganic ions and organic substrates May be highly selective, discriminating between solutes on the basis of subtle differences in chemical structure Often Mediate both passive and active transport (i.e. down and up) the prevailing electrochemical gradients Commonly show saturation kinetics within physiological substrate concentration ranges Competition between structurally similar solutes Commonly show trans stimulation (i.e. acceleration of the unidirectional flux of a solute in one direction by a high concentration of the solute on the opposite side of the membrane) Solute transport is commonly dependent on inorganic ions (typically, but not always, Na + ) Typically s 1 versus transporters rmal function General selectivity Stereoselectivity Thermodynamics Kinetics Substrate competition Trans effects Ion dependence Turnover number Membrane permeation of inorganic ions for the purpose of alteration/stabilisation of the membrane potential and/or bulk ion movements Discriminate between solutes on the basis of gross physical characteristics (size & charge) Transport solutes down (never up) the prevailing electrochemical gradient Saturate at high solute concentrations. though commonly not within physiological ion concentration ranges Don t usually show competition between different ions. Typically s 1 (basis for single channel recordings) Transport of wide range of solutes including inorganic ions and organic substrates May be highly selective, discriminating between solutes on the basis of subtle differences in chemical structure Often Mediate both passive and active transport (i.e. down and up) the prevailing electrochemical gradients Commonly show saturation kinetics within physiological substrate concentration ranges Competition between structurally similar solutes Commonly show trans stimulation (i.e. acceleration of the unidirectional flux of a solute in one direction by a high concentration of the solute on the opposite side of the membrane) Solute transport is commonly dependent on inorganic ions (typically, but not always, Na + ) Typically s 1

9 Passive vs active transport Figure 11 4a Molecular Biology of the Cell ( Garland Science 2008) versus transporters rmal function General selectivity Stereoselectivity Thermodynamics Kinetics Substrate competition Trans effects Ion dependence Turnover number Membrane permeation of inorganic ions for the purpose of alteration/stabilisation of the membrane potential and/or bulk ion movements Discriminate between solutes on the basis of gross physical characteristics (size & charge) Transport solutes down (never up) the prevailing electrochemical gradient Saturate at high solute concentrations. though commonly not within physiological ion concentration ranges Don t usually show competition between different ions. Typically s 1 (basis for single channel recordings) Transport of wide range of solutes including inorganic ions and organic substrates May be highly selective, discriminating between solutes on the basis of subtle differences in chemical structure Often Mediate both passive and active transport (i.e. down and up) the prevailing electrochemical gradients Commonly show saturation kinetics within physiological substrate concentration ranges Competition between structurally similar solutes Commonly show trans stimulation (i.e. acceleration of the unidirectional flux of a solute in one direction by a high concentration of the solute on the opposite side of the membrane) Solute transport is commonly dependent on inorganic ions (typically, but not always, Na + ) Typically s 1

10 versus transporters rmal function General selectivity Stereoselectivity Thermodynamics Kinetics Substrate competition Trans effects Ion dependence Turnover number Membrane permeation of inorganic ions for the purpose of alteration/stabilisation of the membrane potential and/or bulk ion movements Discriminate between solutes on the basis of gross physical characteristics (size & charge) Transport solutes down (never up) the prevailing electrochemical gradient Saturate at high solute concentrations. though commonly not within physiological ion concentration ranges Don t usually show competition between different ions. Typically s 1 (basis for single channel recordings) Transport of wide range of solutes including inorganic ions and organic substrates May be highly selective, discriminating between solutes on the basis of subtle differences in chemical structure Often Mediate both passive and active transport (i.e. down and up) the prevailing electrochemical gradients Commonly show saturation kinetics within physiological substrate concentration ranges Competition between structurally similar solutes Commonly show trans stimulation (i.e. acceleration of the unidirectional flux of a solute in one direction by a high concentration of the solute on the opposite side of the membrane) Solute transport is commonly dependent on inorganic ions (typically, but not always, Na + ) Typically s 1

11 Trans stimulation From Stein (1986) Trans stimulation

12 versus transporters rmal function General selectivity Stereoselectivity Thermodynamics Kinetics Substrate competition Trans effects Ion dependence Turnover number Membrane permeation of inorganic ions for the purpose of alteration/stabilisation of the membrane potential and/or bulk ion movements Discriminate between solutes on the basis of gross physical characteristics (size & charge) Transport solutes down (never up) the prevailing electrochemical gradient Saturate at high solute concentrations. though commonly not within physiological ion concentration ranges Don t usually show competition between different ions. Typically s 1 (basis for single channel recordings) Transport of wide range of solutes including inorganic ions and organic substrates May be highly selective, discriminating between solutes on the basis of subtle differences in chemical structure Often Mediate both passive and active transport (i.e. down and up) the prevailing electrochemical gradients Commonly show saturation kinetics within physiological substrate concentration ranges Competition between structurally similar solutes Commonly show trans stimulation (i.e. acceleration of the unidirectional flux of a solute in one direction by a high concentration of the solute on the opposite side of the membrane) Solute transport is commonly dependent on inorganic ions (typically, but not always, Na + ) Typically s 1

13 Uniporters, symporters, antiporters Pumps (i.e. primary active transporters)