BC351 Lecture 7 Protein Function Membrane Transport Terms Peripheral membrane protein Integral membrane protein Passive diffusion Active diffusion Facilitated diffusion Primary active diffusion Antiports Symports Secondary active diffusion Uniports Principles 1 Membrane protein structure considerations 2 Thermodynamics of membrane transport a Favorable direction b The need for transporters 3 Types of transport and transporters a Specific examples will include proteins found in the intestine I Roles of membrane proteins a Transporters cell surface receptors structural roles exocytosis endocytosis and a variety of other functions b We are concentrating on transport II Membrane protein structure pgs 375 379 a Integral vs peripheral i Definition of a peripheral membrane protein 1 ii Definition of a Integral membrane protein 1 LN07 1 b Integral membrane protein characteristics i It is not favorable to bury hydrophilic electrostatic charges in a membrane without satisfying their bonding potential ii Things to consider in regards to the backbone 1 The peptide backbone is laced with hydrogen bonding acceptors and hydrogen bonding donors O R C N R H a How might the hydrogen bonding potential of the peptide backbone be satisfied in membrane spanning regions of an integral membrane protein b What about the edges of a sheet LN07 2 2 Things to consider in regards to the side chains for a A single membrane spanning helix b Multiple membrane spanning helicies LN07 3 c barrels i Both the barrels and multiple membrane spanning helicies provide a means for the formation of a hydrophilic interior III Thermodynamic considerations pgs 389 393 a Spontaneity and free energy i Concentration gradients 1 Free energy of a concentration gradient is given by a G RT ln c2 c1 2 Our examples lipid 2 2 2 2 2 2 2 2 2 c1 2 2 2 2 lipid lipid 2 2 2 2 2 2 2 2 2 2 2 2 c2 c1 2 2 2 2 2 2 2 c2 LN07 4 2 2 2 2 2 2 2 2 2 2 c1 c2 ii Electrical chemical gradients 1 Free energy of a electrochemical gradient is given by a G RT ln c2 c1 ZF 2 Our example lipid 2 2 2 2 2 2 2 2 2 2 2 c1 2 2 2 c2 a Which way will the Ca2 cations move b BUT will they move b Membrane transporters as catalysts i WHAT IF the diffusion is facilitated by a protein Ca2 left Ca2 right Ca2 left G Ca2 right R C 1 These proteins act to lower the activation energy by providing a hydrophilic environment that allows the hydrophilic solute to pass through the membrane 2 Definition of facilitated diffusion a LN07 5 ii Transport kinetics 1 Rate of transport vo vs S out a Vmax and Kt b An example of specificity and Kt Kt for D glucose Kt for D galactose Kt for L glucose IV A membrane transport system pgs 395 396 403 404 406 a Absorption of glucose i The background 1 Glucose in the cell is higher than in the intestinal lumen 2 BUT glucose must be moved from the intestinal lumen to through the intracellular environment to the blood Intestinal lumen Intracellular glucose low Blood glucose high glucose low 2 1 3 LN07 6 4 Principle 1 Active Diffusion 2 Symports and antiports 3 Secondary active diffusion ii How will this be done 1 Active diffusion a 2 Na glucose symporter a Symporters vs antiporters i ii b Na in vs Na out and Intestinal lumen glucose low Intracellular glucose high 2 1 Na 145mM Blood glucose low 3 4 Na 12mM 0 05V Na 145mM 0 05V TRANSPORTERS CHANNEL TYPE i Gt RT ln C2 C1 ZF ii If all this energy is used how great of a difference between glucose out and glucose in can be made c Secondary Active diffusion i LN07 7 iii How is the intracellular Na maintained 1 ATP powered pumps a Na K ATPase AKA Na K pump Principles 1 Chemically powered pumps a Primary active diffusion i What is the Na in the blood and what is the membrane potential ii Gt RT ln C2 C1 ZF iii Where does this energy come from Intestinal lumen glucose low Intracellular Blood glucose high 2 1 Na 145mM glucose low 3 4 Na 12mM 0 05V Na 145mM 0 05V TRANSPORTERS CHANNEL TYPE 1 Primary active diffusion a LN07 8 iv But what about intracellular glucose 1 Solution a Passive diffusion Principles 1 Passive diffusion 2 Uniports i b GLUT transporters i Uniports 1 Intestinal lumen glucose low Intracellular glucose high 2 1 Na 145mM Blood glucose low 3 4 Na 12mM 0 05V Na 145mM 0 05V TRANSPORTERS CHANNEL TYPE v Finally what maintains the K inside the cell 1 K ion channel LN07 9 2 Ion channels a Features i Move only Ions ii Always in the thermodynamically favored direction iii VERY rapid rates 107 108 ions s ION CHANNELS ION CHA NNELS 1 Move only ions 2 Never via active transport 3 V ery rapid rates of transport 4 Do not exhibit saturation behavior v0 CARRIERS 1 Move ions and other molecules 2 Can be passive or active 3 Slow er rates of transport 4 Do exhibit saturation behavior v0 S S LN07 10