1. II Structure and Catalysis 5. Amino Acids, Peptides, and Proteins 6. The Three-Dimensional Structure of Proteins 7. Protein Function 8. Enzymes 9. Carbohydrates and Glycobiology 10. Lipids 11. Biological Membranes and Transport 12. Biosignaling

2. Major Membrane Transport Proteins 1.Passive Transporters a) Channel Proteins (Aquaporin) b) Carriers (Glucose Transporter) c) Exchangers (Chloride-Bicarbonate Exchanger) 2. Active Transporters (ATP-Powered Pump) a)P-Type ATPase (Na+K+ATPase, Ca ++ Pump) b)V-Type ATPase (H + Pump or ATPase/ATP synthase) c)F-Type ATPase (H+ Pump) d)ABC Transporters (Multidrug Transporter)

3. Channel proteins; transport water or specific types of ions down their concentration (or electric potential) gradients with no binding with their substrates and energetically favorable reactions. They form a protein-lined passageway across the membrane. For example; Aquaporins, Na + and K + Channels

4. Aquaporins; A family of integral proteins, provide channels for rapid movement of water molecules across plasma membranes in variety of specialized tissues. All aquaporins are type III integral protein with six transmembrane helical segments.

6. K + Channel; consists of four identical subunits that span the membrane and form a cone within a cone surrongding the ion channel, with wide end of the double cone facing the extracellular space

7. Structure and function of K + Channel

8. Glucose transporter; any sugar-transport protein for which glucose is a substrate. In erythrocytes, it is a type III integral protein (Mr 45,00) with 12 hydrophobic segments, each of which form a membrane-spanning helix. The side- by-side assembly of several helices produces a transmembrane channel lined with hydrophilic residues that can hydrogen bond with glucose as it moves through the channel.

9. Glucose transporter

10. The Glucose Transporter of Erythrocytes Mediate passive Transport

11. Model of glucose transport into erythrocytes 1.Glucose in blood plasma binds to a stereospecific site. 2.Lowing the activation energy for a conformation change from S out T 1 to S in T 2. 3.glucose is released from T 2 into cytosol. 4.The transporter returns to the T1 conformation and ready to transport another glucose molecule.

13. Regulation of Glucose Transport

14. Exchanger; mediates the simultaneous movement of two anions with no net transfer of charge (electroneutral). For example; Chloride-bicarbonate exchanger Chloride-bicarbonate exchanger; is an integral protein that spans the membrane 12 times. This protein mediates the simultaneous movement of two anions; for each HCO 3 ion that moves in one direction, one Cl - ion moves in the opposite direction.

15. Chloride and Bicarbonate Are Cotransported across the Erythrocyte Membrane Waste CO 2 released from respiring tissues into the blood plasma enters the erythrocyte, where it is converted into bicarbonate (HCO 3 ) by the enzyme carbonic anhydrase ( 脱水酶 ). The HCO 3 reenters the blood plasma for transport to the lungs. In the lungs, HCO 3 reenters the erythrocyte and is converted to CO 2, which is eventually exhaled. For this shuttle to be effective, very rapid movement of HCO 3 across the erythrocyte membrane is required.

16. Major Membrane Transport Proteins 1.Passive Transporters a) Channel Proteins (Aquaporin) b) Carriers (Glucose Transporter) c) Exchangers (Chloride-Bicarbonate Exchanger) 2. Active Transporters (ATP-Powered Pump) a)P-Type ATPase (Na+K+ATPase, Ca ++ Pump) b)V-Type ATPase (H + Pump or ATPase/ATP synthase) c)F-Type ATPase (H+ Pump) d)ABC Transporters (Multidrug Transporter)

17. Active Transport Results in Solute Movement against a Concentration or Electrochemical Gradient Two types of active transport: 1.Primary active transport, the energy release by ATP hydrolysis drives solute movement against an electrochemical gradient. 2.Secondary active transport, movement of X down its electrochemical gradient then provides the energy to drive cotransport of second solute against its electrochemical gradient.

18. ATP-powered pumps (pumps); are ATPases that use energy of ATP hydrolysis to move ions across a membrane against a chemical concentration gradient or electric potential. This type of ion movement is a coupled chemical reaction in which an energetically unfavorable reaction (against a concentration gradient or membrane potential).

19. P-Type ATPase: undergo phosphorylation during their catalytic cycles. They have similarities in amino acid sequence. They are integral protein with ten predicated membrane-spanning regions in a single polypeptide. For example; Na + K + ATPase and Ca ++ ATPase

20. Na + K + ATPase (Pump); Virtually every animal cell maintains a lower concentration of Na + and a higher concentration of K + than is found in its surrounding medium (in vertebrates, extracellular fluid or the blood plasma). This imbalance is established and maintained by a primary active transport system in the plasma membrane, involving the enzyme Na + K + ATPase (discovered by Jens Skou in 1957), which couples breakdown of ATP to the simultaneous movement of both Na + and K + against their concentration gradients.

22. Postulated mechanism of Na + and K + transport by the Na + K + ATPase. 1.Three Na+ bind to high-affmity sites on the transport protein. Phosphorylation of the transporter changes its conformation. 2.Decreases its affinity for Na +, leading to Na + release on the outer surface. 3.Next, K + on the outside binds to high affinity sides on the extracellular portion. 4.The enzyme is dephosphorylated, reducing its affinity for K +. 5.K + is discharged on the inside. 6.The transport protein is now ready for another cycle of Na + and K + pumping.

23. A P-Type ATPase Catalyzes Active Cotransport of Na + and K + Ouabain (pronounced 'wa- ban), a steroid derivative extracted from the seeds of an African shrub, is a potent and specific inhibitor of' the Na + K + ATPase. Ouabain is a powerful poison used to tip hunting arrows.

24. Ca ++ ATPase (Pump); The cytosolic concentration of Ca ++ is generally at or below 100mM, far lower than that in the surrounding medium. The ions are pumped out of the cytosol by a P-Type ATPase. One is the plasma membrane Ca ++ Pump and another is the sarcoplasmic and endoplasmic reticulum Ca ++ pump.

25. Structure of the Ca++ pump of sarcoplasmic reticulum

26. Ion selective channel are gated; opened or closed in response to some cellular event. The gating can be very fast with only milliseconds, making these molecular devices effective for very fast signal transmission in the nervous system.

27. Gated Channels 1.Ligand-gated channel; binding of an extracellular or intracellular small molecule forces an allosteric transition in the protein, which opens or close the channel, for example; Nicotinic Acetylcholine Receptor 2.Voltage-gated channel; a change in transmembrane electric potential causes a charged protein domain to move relative to the membrane, opening or closing the ion channel, for example, Neuronal voltage-gated Na + Channel.

28. Nicotinic Acetylcholine Receptor; is essential in the passage of an electrical signal from a motor neuron to a muscle fiber at the neuromuscular junction. Acetylcholine released by motor neuron diffuses to membrane of myocyte, where it binds to the acetylcholine receptor and lead to conformational change in the receptor, finally causing the ion channel intrinsic to the receptor to open. The resulting inward movement of positive charges depolarizes the plasma membrane of myocyte, triggering constraction.

29. The Acetylcholine Receptor Is a Ligand-Gated Ion Channel

30. The Acetylcholine Receptor

31. The Acetylcholine Receptor Is a Ligand-Gated Ion Channel

32. Neuroal voltage-gated Na + channels; sense electrical gradients across the membrane and respond by opening or closing. They are typically very selective for Na + over other monovalent or divalent cations and have a very high flux rate. Normally in the closed conformation, Na + channels are activated by reduction in the transmembrane electrical potential. They then undergo very rapid inactivation. Within milliseconds of the opening, the channel closes and remains inactive for many milliseconds. Activation followed by inactivation of Na + channels is the basis for signaling by neurons.

33. The Neuronal Na + Channel Is a Voltage- Gated Ion Channel

37. Ion-Channel Function Is Measured Electrically