1. 18-1 Principles and Applications of Inorganic, Organic, and Biological Chemistry Denniston, Topping, and Caret 4 th ed Chapter 18 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Power Point to Accompany

2. 18-2 18.1 Lipids Lipids- a collection of organic molecules united by solubility in nonpolar solvents. Varying chemical composition Four main groups

3. 18-3 Main Groups 1.Fatty acids Saturated and unsaturated 2. Glycerides Contain glycerol (HOCH 2 CHOHCH 2 OH) 3. Nonglycerides Sphingolipids, steroids, waxes 4. Complex lipids lipoproteins

4. 18-4 Lipid Functions As an energy source, lipids provide 9 kcal of energy per gram. Triglycerides provide energy storage in adipocytes. Phosphoglycerides, sphingolipids, and steroids are part of cell membranes. Steroid hormones are critical intercell messengers. Lipid soluble vitamins (A, E, D, E) Provide shock absorption and insulation.

5. 18-5 18.2 Fatty Acids Lauric acid: a typical saturated fatty acid with 12 carbons in the chain (in salt form) Fatty acid: 12-20 carbons, even # carbons, no branching, nonpolar carbon chain, polar COO - group (as anion). Nonpolar hydrophobic tail “ Polar” hydrophilic head 2

6. 18-6 Fatty Acids-2 An unsaturated fatty acid has one or more carbon-carbon double bonds in the chain. The first double bond is usually at the ninth carbon. The double bonds are not conjugated and are usually cis. Palmitoleic acid, salt form Cis double bond results in a bent chain and lower mp. 2

7. 18-7 Fatty Acids-3 Stearic 18:0 (# of C and double bonds) CH 3 (CH 2 ) 16 COOH Palmitoleic 16:1  9 (  9 position of double bond ) CH 3 (CH 2 ) 5 CH=CH (CH 2 ) 7 COOH Linolenic 18:2  9,12 CH 3 (CH 2 ) 4 CH=CHCH 2 CH=CH(CH 2 ) 7 CO Arachidonic20:4 ,8,11,14 CH 3 (CH 2 ) 3 (CH 2 CH=CH) 4 (CH 2 ) 3 COOH

8. 18-8 Fatty Acid Properties Mp increases with carbon number. Mp of saturated acid is higher than an unsaturated acid of same carbon number. cis double bond prevents good alignment of molecules in unsaturated fatty acids. Lowers mp relative to saturated or trans acid.

9. 18-9 Fatty Acid Reactions-1 Esterification Acid Hydrolysis

10. 18-10 Fatty Acid Reactions-2 Saponification Hydrogenation of Double Bonds

11. 18-11 Eicosanoids: Prostaglandins, etc. Arichadonic acid (20 carbons) is the eichosanoid presursor. Prostaglandins have hormonelike activity. In PGF 2, PG stands for prostaglandin; F for a particular group with OH on C-9; and the 2 indicates two double bonds.

12. 18-12 Prostaglandin Function Stimulation of smooth muscle Regulation of steroid biosynthesis Inhibition of gastric secretion Inhibition of hormone-sensitive lipases Inhibition of platelet aggregation Stimulation of platelet aggregation Regulation of nerve transmission Sensitization to pain Mediation of inflammatory response

13. 18-13 Aspirin and Prostaglandins Aspirin inhibits prostaglandin synthesis by acylating cyclooxygenase, an enzyme necessary for prostaglandin synthesis. Acylated enzyme

14. 18-14 18.3 Glycerides: Triacylglycerols When all three alcohol groups of glycerol form esters with fatty acids a neutral triacylglycerol (triglyceride) is formed. Triglycerides serve as energy storage in adipose cells. Fatty acid chains Glycerol part

15. 18-15 Phosphoglycerides Have hydrophobic and hydrophilic domains. Structural components of membranes Emulsifying agents Suspended in water they spontaneously rearrange into ordered structures Hydrophobic group to center Hydrophilic group to water (Basis of membrane structure)

16. 18-16 Phosphoglycerides-2 When the third OH of glycerol is esterified to a phosphoric acid or a phosphoric acid ester instead of a carboxylic acid, a phosphoacylglycerol results. Phosphatidic acid Phosphatidic ester

17. 18-17 Phosphatidyl esters, egs. Lecithin has a polar head and is amphipathic. It is the major phospholipid in pulmonary surfactant and an emulsifying agent.

18. 18-18 18.4 Nonglyceride Lipids: Sphingolipids These lipids are based on sphingosine, are found in plants and animals, and are common in the nervous system.

19. 18-19 Sphingolipids-2 A ceramide N-acylsphingosine A sphingomyelin Essential to cerebral function and nerve transmission.

20. 18-20 Glycolipids or Glycosphingolipids Frequently a glucose or galactose is bound to the primary alcohol of a ceramide. The compound is called a cerebroside. These compounds are found in the cell membranes of nerve and brain cells. A cerebroside

21. 18-21 Glycolipids-2: Gangliosides Gangliosides have oligosaccharide groups with one or more sialic acid (N- acetylnuraminic acid) residues attached. Names include M, D, T (# residues) and subscripts for number of sugars attached to the ceramide. See the next slide for the structure of a ganglioside associated with Tay-Sachs an autosomal recessive disease resulting in neurological deterioration.

22. 18-22 Gangleoside GM 2 Sph=ceramide

23. 18-23 Sphingolipid Storage Diseases DiseaseSympt.Sph. LipEnzyme Tay-SachsBlindness, muscle weakenss Ganglioside GM 2  -hexose- aminidaseA Gaucher’sLiver and spleen enlarge, MR Glucocer- ebroside  -glucos- idase Krabbe’sdemyelation, MR Galactocer- ebroside  -galactos- idase Nieman- Pick MRSphingo- myelin Sphingomy- elinase

24. 18-24 Steroids Steroids are synthesized from the five carbon isoprene unit and are part of a diverse collection of lipids called isoprenoids. They also fit into the terpene classification.

25. 18-25 Steroids-2 Steroid lipids are based on the ring system shown below. The next slide shows some examples of steroid sex hormones and of cholesterol, a lipid very important in human physiology.

26. 18-26 Steroid Examples

27. 18-27 Wax Esters Waxes are typically esters of fatty acids and fatty alcohols. They protect the skin of plants and fur of animal etc. Examples of waxes include carnuba, from the leaves of the Brasilian wax palm, and beeswax.

28. 18-28 18.5 Complex Lipids Lipoproteins The term is most often used for molecular complexes found in blood plasma of humans. Contain: neutral lipid core of cholesterol esters and/or TAGs surrounded by a layer of phospholopid, cholesterol, and protein. Classes: chylomycrons, VLDL, LDL, HDL

29. 18-29 Lipoproteins-2 Chylomycrons: very large and very low density; transport intestine  adipose VLDL: made in liver; transport lipids to tissues; depleted one to LDLs. LDL: carry cholesterol to tissues HDL: made in liver; scavenge excess cholesterol esters; “good cholesterol”

30. 18-30 Atherosclerosis Atheromas (plaque) impede blood flow. Plaque: smooth muscle cells, macrophages, cell debris Macrophages fill with LDLs Coronary artery disease a very common consequence. High plasma concentrations of LDLs correlate with risk.

31. 18-31 Membrane Receptors The LDL receptor was discovered during an investigation of familial hypercholesterolemia. When a cell needs cholesterol, it synthesizes the receptor which migrates to a coated region of the membrane. The “captured” cholesterol is absorbed by endocytosis. Failure to make the receptor is the most common problem encountered.

32. 18-32 18.6 Membranes Each type of cell has a unique membrane composition with varying percentages of lipids, proteins, and some carbohydrates. The currently accepted model of the membrane is the fluid mosaic model of a lipid bilayer. Some examples follow on the next slide.

33. 18-33 Composition of Some Membranes Protein %Lipid %Carb. % Human erythrocyte 49 43 8 Mouse liver 46 54 2-4 Mitochon- drial (inner) 76 24 1-2 Spinach lamellar 70 30 6 G Guidotti, Ann Rev Biochem, 41:731, 1972

34. 18-34 Membrane Lipids 1.Fluidity Lateral movement of phospholipids is rapid. Flip-flop, from one side to the other is rare. Increasing percentage of unsaturated fats leads to more fluidity. See next slide.

35. 18-35 A fluid membrane model

36. 18-36 Membrane Lipids-2 2. Selective permeability The hydrophobic nature of the membrane makes it impenetrable to the transport of ionic and polar substances. Membrane proteins regulate passage of ionic and polar substances by binding to the polar compound or by providing a channel.

37. 18-37 Membrane Lipids-3 3. Self-sealing capacity A break in the membrane immediately and spontaneously seals. 4. Asymmetry Bulkier molecules occur more often in the inner side of the membrane.

38. 18-38 Membrane Proteins Most membranes require proteins to carry out their functions. Integral proteins are embedded in and/or extend through the membrane. Peripheral proteins are bound to membranes primarily through interactions with integral proteins.

39. 18-39 Membrane Transport The cell membranes is responsible for the controlled passage of molecules and ions into and out of cells and organelles. Binding of hormones and other biomolecules. With passive transport, there is net movement of solute to a region of lower concentration (diffusion) With facilitated diffusion, a membrane protein (a permease) assists in diffusion. The process still requires no energy and is passive.

40. 18-40 Membrane Transport-2 Passive transport (no direct energy input) Simple diffusion-molecules move through a membrane down a concentration gradient (toward lower concentration). Facilitated diffusion-molecules move through protein channels in membrane.

41. 18-41 Osmosis Osmosis is the net flow of water through a semipermeable membrane (ie. Cell wall) from a region of low solute concentration to a region of high solute concentration. Osmotic pressure is that which must be applied to prevent flow of water across the membrane.

42. 18-42 Osmosis, cont. If a cell has a higher osmotic concentration than the surrounding fluid, it’s fluid is said to be hypertonic. Water flows into the cell and it may burst or hemolyze. If a cell has a lower osmotic concen- tration than the surrounding fluid, it’s fluid is said to be hypotonic. Water flows out og the cell and it shrinks or crenates..

43. 18-43 Membrane Transport-3 Facilitated diffusion Chemically or voltage-regulated e. g. acetyl choline binds to a receptor; Na + rushes into the cell causing depolarization which in turn opens a voltage gated channel for Na +. Repolarizaton begins when a voltage- gated K + channel opens and K + leave the cell.

44. 18-44 Membrane Transport-4 Facilitated diffusion (cont.) A carrier protein binds to a molecule. The protein changes conformation and releases the molecule into the cell. This process speeds diffusion but cannot cause a net increase in solute concentration over diffusion limits.

45. 18-45 Membrane Transport-5 Active transport Primary-energy provided by ATP e. g. the Na + -K + pump (Next slide) Secondary-concentration gradients generated by primary active transport are used to move substances across membranes. e. g. Na + gradient (Na + -K + pump) used to transport glucose in kidney tubules.

46. 18-46 Sodium-Potassium Pump Insert Fig 18.21

47. 18-47 Membrane Transport-6 Cystic fibrous is a result of a missing or defective plasma membrane glycoprotein called cystic fibrosis transmembrane conductance regulator (CFTR) which functions as a chloride channel in epithelial cells. In CF, chloride is retained in the cells, thick mucous forms due to osmotic uptake of water in the cells. Chronic pulmonary problems and infections result.

48. 18-48 The End Lipids