Chem Lecture 9 Pumps and Channels Part 1

Transcription

1 Chem 45 - Lecture 9 Pumps and Channels Part 1 Question of the Day: What two factors about a molecule influence the change in its free energy as it moves across a membrane? Membrane proteins function as Pumps (Chapter 13) Channels (Chapter 13) Signal transducers (Chapter 14) Energy transducers (Chapter 18 & 19) Membrane proteins function as Pumps (Chapter 13) Channels (Chapter 13) Signal transducers (Chapter 14) Energy transducers (Chapter 18 & 19) 3 Membrane Lipids and Water Lipid membranes display a wide range of permeability's to small molecules. Chem 45, Lecture 8 - Lipids and Cell Membranes 4

2 Pumps and Channels move substances across membranes. Pumps move substances from regions of low concentration to high concentration. Requires a source of energy (active transport) Channels allow substances to move from regions of high concentration to low concentration. Does not require an outside source of energy (passive transport) If passive transport requires a channel it is called facilitated diffusion. 5 Some pumps couple transport to the hydrolysis of ATP (primary transport) P-Type ATPases ATP-binding cassette (ABC) transporters And some pumps couple transport to a second concentration gradient (secondary transport) 6 Transporters are used to regulate the metabolic in different tissues across an organism. e.g. Glucose Transporters 7 Transporters are used to regulate the metabolic in different tissues across an organism. e.g. Glucose Transporters Which tissue is last in line to take up glucose from the blood? 7

3 Transporters are used to regulate the metabolic in different tissues across an organism. e.g. Glucose Transporters Which tissue is last in line to take up glucose from the blood? 7 Transporters are used to regulate the metabolic in different tissues across an organism. e.g. Glucose Transporters 7 Gated channels, while not requiring energy for transport, can be highly specific. The Potassium Channel 8 Active versus Passive Transport! Transport across membranes Simple Diffusion (passive transport) Facilitated diffusion (passive transport) Requires energy (active transport) For all kinds of transport, the G for the process must be < 0. 9

4 Active versus Passive Transport! 10 Active versus Passive Transport! Concentration 10 Active versus Passive Transport! Concentration 10 Active versus Passive Transport! Concentration 10

5 Active versus Passive Transport! Concentration Voltage 10 Active versus Passive Transport! Concentration Voltage 10 Active versus Passive Transport! Concentration Voltage 10 ATPase Pumps (Active Transport)! P-type ATPases ATP-Binding Cassette Transporters Conformational changes are coupled to ATP hydrolysis 11

6 ATPase Pumps (Active Transport)! P-type ATPases ATP-Binding Cassette Transporters Conformational changes are coupled to ATP hydrolysis 11 ATPase Pumps (Active Transport)! P-type ATPases ATP-Binding Cassette Transporters Conformational changes are coupled to ATP hydrolysis 11 P-type ATPases Na + /K + ATPase Pumps 3 Na + out while pumping K + in. Gastric H + /K + ATPase Sarcoplasmic Ca + ATPase (SERCA) 1 The energetics of active transport Na + /K + ATPase Pumps 3 Na + out while pumping K + in. -50 kj/mol 14 mm (-) (+) -50 mv mm 157 mm 4 mm 13

7 The energetics of active transport Na + /K + ATPase Pumps 3 Na + out while pumping K + in. 3 Na + in + K + out 3 Na + out + K + in kj = x 10 3 ( 0.143) mol K ( 3 ( 0.157) 310 K)ln ( 0.014) 3 ( 0.004) + ( +1) 96.5 kj mol V ( V) kj = 36.9 mol kj mol kj = 41.7 mol 14 SERCA (Sarcoplasmic Reticulum Ca + ATPase) Have crystal structure for each step in pumping cycle 15 SERCA (Sarcoplasmic Reticulum Ca + ATPase) Have crystal structure for each step in pumping cycle 15 SERCA (Sarcoplasmic Reticulum Ca + ATPase) Have crystal structure for each step in pumping cycle 15

8 SERCA Phosphorylation of an aspartate (A351) causes a conformational change that disrupts the Ca + binding sites. 16 SERCA 17 The drug digitoxigenin (digitalis), which is used to treat congestive heart failure, inhibits the Na + /K + ATPase. 18 The P-type pumps are homologous. The drug digitoxigenin (digitalis), which is used to treat congestive heart failure, inhibits the Na + /K + ATPase. 19

9 The P-type pumps are homologous. The drug digitoxigenin (digitalis), which is used to treat congestive heart failure, inhibits the Na + /K + ATPase. Foxglove (Digitalis purpurea) 0 The P-type pumps are homologous. The drug digitoxigenin (digitalis), which is used to treat congestive heart failure, inhibits the Na + /K + ATPase. With higher cellular Na + levels, the Ca + pump is slower to remove the Ca + from the cytoplasm, leading to a stronger contraction. 1 The P-type pumps are homologous. The drug digitoxigenin (digitalis), which is used to treat congestive heart failure, inhibits the Na + /K + ATPase. With higher cellular Na + levels, the Ca + pump is slower to remove the Ca + from the cytoplasm, leading to a stronger contraction. 1 The P-type pumps are homologous. Yeast contain 16 examples H + Ca + Na + Cu + phospholipid (flipases)

10 The P-type pumps are homologous. Yeast contain 16 examples H + Ca + Na + Cu + phospholipid (flipases) The ATP-binding (ABC) Transporter. Uses a slightly different strategy from the P-type ATPases. 3 The ATP-binding (ABC) Transporter. Uses a slightly different strategy from the P-type ATPases. lipid transporter (Vibrio cholera) 4 The ATP-binding (ABC) Transporter. Uses a slightly different strategy from the P-type ATPases. 5

11 Secondary Transporters! Secondary transporters are active transport systems that do not derive their energy directly from the hydrolysis of ATP Instead, the active transport is coupled to the passive transport of a second metabolite 6 Secondary Transporters! Lactose Permease is a well-studied example. 7 Secondary Transporters! The transport of lactose up a concentration gradient is coupled to the transport of protons down a concentration gradient. 8 Secondary Transporters! The transport of lactose up a concentration gradient is coupled to the transport of protons down a concentration gradient. Is lactose permase a symporter or an antiporter? 8

12 Next up Unit V, Lecture 9, con d - Membrane Channels and Pumps. (Chapter 13) K + channel and the action potential 9