1. Transport Through Membranes

2. Necessity for Transport Plasma Membranes Intracellular Membranes (Organelles)

3. Biological Membranes Organized assemblies of lipids, proteins and small amounts of carbohydrates Regulate composition of intracellular medium by controlling flow of nutrients, waste products, ions, etc. in and out of cell Scaffolding –Oxidative phosphorylation –Photosynthesis –Nerve impulses –Hormone receptors

4. Membrane Lipids Generally soluble in organic solvents

5. Types of Membrane Lipids Glycerophospholipids Sphingolipids Cholesterol

6. Glycerophospholipids (Glycerol 3-phosphate)

7. Phosphatidic Acid (1,2-diacylglycerol-3-P)

8. Membrane Glycerophospholipids

9. Fatty Acids Saturated and unsaturated Amphiphilic

10. Glycerophospholipid Alcohols Ethanolamine Serine Choline

11. Amphiphilicity

12. Sphingolipids (Sphingosine)

13. Sphingolipids (Sphingomyelin) Myelin Sheath – defective in some metabolic diseases

14. Cholesterol

15. Properties of Cholesterol Highly hydrophobic (low solubility) Lowers melting point of mixed lipids Stiffens surface proximal region of bilayer

16. Occurrence of Cholesterol Animal plasma membranes Organelle membranes (some) Precursor to steroid hormones

17. Properties of Lipid Aggregates Monolayers, Micelles and Bilayers

18. Monolayers (very dilute solutions)

19. Micelles (single-tailed lipids) Critical Micelle Concentration

20. Cylindrical Lipids

21. Bilayers

22. Liposomes

23. Properties/Uses of Liposomes Single Bilayer (inner and outer leaflets) Delivery of Therapeutic Agents

24. Membrane Proteins Peripheral or Extrinsic Proteins Integral or Intrinsic Proteins

25. Peripheral or Extrinsic Proteins Easily dissociated –High ionic strength –pH chages Free of attached lipid (dissociated) Water-soluble (e.g. cytochrome c) Normal amino acid composition

26. Integral or Intrinsic Proteins Not easily dissociated Retain associated lipid (dissociated) >average hydrophobic amino acds Significant number hydrophilic amino acds Asymmetrically oriented amphiphiles Trans-membrane proteins

27. Asymmetric Orientation

28. Integral or Intrinsic Proteins

29. Membrane Carbohydrates Mostly oligosaccharides Variety of sugars Often sialic acid Glycolipids Glycoproteins

30. Membrane Structure

31. Fluid Mosaic Model

32. Membrane Permeability (Impermeable to Most Polar Substrates)

33. Thermodynamics of Transport

34. Move Toward Equilibrium

35. Move from Higher Concentration to Lower Concentration No information about rate of movement!

36. Kinetics and Mechanisms of Transport

37. Types of Transport Nonmediated Transport (Diffusion) Mediated Transport (Transport Proteins) –Passive-mediated Transport (facilitated diffusion) –Active Transport

38. Terminology Carriers Permeases Porters Translocases Translocators Transporters

39. Non-mediated Transport (Permeability Coefficient)

40. Mediated Transport (Transport Proteins)

41. Mediated Transport Properties Saturation kinetics Speed and specificity Susceptibility to competitive inhibition Susceptibility to chemical inactivation

42. Asymmetric Orientation

43. Types of Transporters

44. Ionophores

45. Valinomycin

46. Gramicidin

47. Stoichiometry

48. Electrical Character Electroneutral Electrogenic

49. Passive-Mediated Glucose Transport Erythrocyte Glucose Transporter

50. Asymmetric Orientation

51. Conformational Change

52. Insulin Action (Muscle and Adipocytes)

53. ATP-Driven Active Transport Against a concentration gradient Often coupled to ATP hydrolysis

54. Na + -K + -ATPase of Plasma Membrane (Reaction)

55. Electrogenic Antiport

56. Mechanism

58. Mechanistic Steps Na + -dependent ATP Phosphorylation of Aspartic Acid Side Chain K + -dependent Hydrolysis

59. Mechanistic Evidence

60. Group Translocation Simultaneous Transport and Chemical Modification

61. PEP-dependent Phosphotransferase System (PTS)

62. EIII g Inhibits Lactose Permease Inhibits Glycerol Kinase

63. Hpr: Histidine-containing phosphocarrier protein

64. Ion Gradient-Driven Active Transport Free Energy of Electrochemical Gradient (Established by ion-pumping) Power Endergonic Physiological Processes

65. Na + -Glucose Symport (Mechanism)

66. Na + -Glucose Symport (Function)

67. Lactose Permease