1. Chapter 11 Lipids and Membranes

2. Lipids Biomolecules defined in terms of solubility:  Insoluble in water but soluble in nonpolar solvents.  Waxy, greasy or oily compounds. Biological Functions:  Energy Storage  Structural component of cell membranes  Signaling molecules Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011 Two major classes 

3. Saponifiable Lipids Saponification: base hydrolysis of esters to produce carboxylic acid salt and alcohol Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011 Simple Lipids: – Contain fatty acids and alcohols Complex Lipids: – Contain multiple fatty acids, alcohol, something else

4.  Fatty Acids  CA’s with long hydrocarbon chains (12 to 20 or more carbons, usually even numbers)  Numbered from the carboxylate end, and the  - carbon is adjacent to the carboxylate group  Terminal methyl carbon is denoted the omega (  ) carbon  Components in triacylglycerols and phospholipids Figure 11.1 Fatty Acid Structure Section 11.1: Lipid Classes

5. Characteristics of Fatty Acids 1. Straight chain (unbranched) carboxylic acids 2. Comprised of 10-20 carbons 3. Usually have even number of carbons 4. Can be saturated or unsaturated 5. Usually no other functional groups Unsaturated fatty acids usually contain double bonds in the cis configuration, and can be mono- or poly-unsaturated This creates kink or bend in chain that prevents unsaturated fatty acids from packing together closely unlike saturated fatty acids – Results in weaker intermolecular forces, lower MP’s – Usually liquid at room temp unsaturated saturated Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011

6. Section 11.1: Lipid Classes

7. Properties of Unsaturated Fatty Acids Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011 The kink or bend in chain of unsaturated fatty acids prevents from packing together closely unlike saturated fatty acids – Results in weaker intermolecular forces, lower MP’s – Increases fluidity of biological membranes

8.  Plants and bacteria can synthesize all fatty acids they require from acetyl-CoA  The human body can synthesize nonessential fatty acids, while essential fatty acids must be acquired from the diet  Essential Fatty Acids  Linoleic acid (omega-6 fatty acid)  Linolenic acid (omega-3 fatty acid) Section 11.1: Lipid Classes Diets rich in omega-3 fatty acids may:  decrease serum cholesterol, triglycerides  reduce risk of heart disease  Fish  Nuts  Kidney Beans Sources of omega-3 fatty acids:  Spinach  Broccoli and cauliflower  Oils

9.  Eicosanoids  Omega-3 and Omega-6 fatty acids are the source of Eicosanoids  Hormone-like signaling molecules  Include:  Prostaglandins: Involved in inflammation, digestion, and reproduction  Thromboxanes: Involved in platelet aggregation and vasoconstriction following tissue injury  Leukotrienes: White blood cell chemoattractants; involved in vasoconstriction, edema, and bronchoconstriction Section 11.1: Lipid Classes

10. Structures of Fats and Oils Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011 Fats: Triglycerides from animal (saturated) Oils: Triglycerides from vegetables (unsaturated) These are esters (alcohol + acid) Alcohol derived from glycerol Acid from fatty acids Most common lipids triglyceride

11.  Fats are solid at room temperature and have a high saturated fatty acid composition  Oils are liquid at room temperature and have a high unsaturated fatty acid composition Figure 11.6 Space-Filling and Conformational Models of a Triacylglycerol Section 11.1: Lipid Classes

12.  Roles in animals: energy storage (also in plants), insulation at low temperatures, and water repellent for some animals’ feathers and fur  Better storage form of energy for two reasons: 1. Hydrophobic and coalesce into droplets; store an equivalent amount of energy in about one-eighth the space 2. More reduced and thus can release more electrons per molecule when oxidized Figure 11.5 Triacylglycerol Section 11.1: Lipid Classes

13. Reactions of Triglycerides Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011 hydrolysis saponification hydrogenation triglyceride Ester of 3 alcohols, 3 acids

14. Chemical Properties of Fats and Oils Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011 Triglycerides exhibit chemical properties of esters and alkenes Rxn: Hydrolysis Breakdown of cellular fats to supply energy begins with lipase catalyzed hydrolysis reaction

15. Chemical Properties of Fats and Oils Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011 Rxn: Saponification Soapmaking (up to AD 500), by adding base (lye or aqueous extract of wood ash) to animal fat

16. Chemical Properties of Fats and Oils Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011 Rxn: Hydrogenation Results in partial hydrogenation (partially-hydrogenated vegetable oils) Semi-solids that don’t separate  Crisco

17.  Wax Esters  Waxes are complex mixtures of nonpolar lipids  Protective coatings on the leaves, stems, and fruits of plants and on the skin and fur of animals  Wax esters composed of long-chain fatty acids and long-chain alcohols are prominent constituents of most waxes  Examples include carnuba (melissyl cerotate) and beeswax Figure 11.8 The Wax Ester Melissyl Cerotate Section 11.1: Lipid Classes

18.  Phospholipids  Amphipathic (hydrophilic and lipophilic) with a polar head group (phosphate and other polar or charged groups) and hydrophobic fatty acids  Act in membrane formation, emulsification, and as a surfactant (lowers surface tension between liquids)  Spontaneously rearrange into ordered structures when suspended in water Figure 11.9 Phospholipid Molecules in Aqueous Solution Section 11.1: Lipid Classes

19.  Two types of phospholipids: phosphoglycerides and sphingomyelins  Sphingomyelins contain sphingosine instead of glycerol (also classified as sphingolipids)  Phosphoglycerides contain a glycerol, fatty acids, phosphate, and an alcohol  Simplest phosphoglyceride is phosphatidic acid composed of glycerol-3-phosphate and two fatty acids  Phosphatidylcholine (lecithin) is alcohol esterified to the phosphate group as choline Section 11.1: Lipid Classes

20. Phosphoglycerides Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011 Complex lipids Serve as major components of cell membranes Also known as phospholipids Structure similar to triglycerides triglyceride phosphoglyceride

21. Phosphoglycerides Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011 The most common phosphoglycerides have choline, ehanolamine, or serine attached to the phosphate group.

22.  Another phosphoglyceride, phosphatidylinositol, is an important structural component of glycosyl phosphatidylinositol (GPI) anchors  GPI anchors attach certain proteins to the membrane surface  Proteins are attached via an amide linkage Figure 11.10 GPI Anchor Section 11.1: Lipid Classes

23.  Phospholipases  Hydrolyze ester bonds in glycerophospholipid molecules  Three major functions: membrane remodeling, signal transduction, and digestion Figure 11.11 Phospholipases Section 11.1: Lipid Classes

24.  Toxic Phospholipases— various organisms use membrane-degrading phospholipases as a means of inflicting damage  Bacterial  -toxin (creates pores in cells leading to apoptosis) and necrosis from snake venom (PLA 2 ) Section 11.1: Lipid Classes

25.  Sphingolipids  Complex lipid found in cell membrane  Contain sphingosine instead of glycerol Section 11.1: Lipid Classes

26.  Sphingomyelin is found in most cell membranes, but is most abundant in the myelin sheath of nerve cells Section 11.1: Lipid Classes https://www.premedhq.com/myelin-sheath-schwann-cells

27.  The ceramides are also precursors of glycolipids  A monosaccharide, disacchaaride, or oligosaccharide attached to a ceramide through an O-glycosidic bond  Most important classes are cerebrosides, sulfatides, and gangliosides (may bind bacteria and their toxins) Figure 11.14a Selected Glycolipids Section 11.1: Lipid Classes

28. Glycolipids Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011 Another type sphingolipid Contain carbohydrates AKA cerebrosides due to abundance in brain tissue No phosphate linkage

29. Related Diseases Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011 Some human diseases are related to abnormal accumulation of sphingomyelins and glycolipids

30.  Isoprenoids  Biomolecules containing repeating five-carbon structural units, or isoprene units  Isoprenoids consist of terpenes and steroids  Terpenes are classified by the number of isoprene units they have  Monoterpenes (used in perfumes), sesquiterpines (e.g., citronella, 3 isoprene units), tetraterpenes (e.g., carotenoids, 8 isoprene units) Figure 11.15 Isoprene Section 11.1: Lipid Classes

31.  Carotenoids are the orange pigments found in plants  Mixed terpenoids consist of a nonterpene group attached to the isoprenoid group (prenyl groups)  Include vitamin K and vitamin E Figure 11.16 Vitamin K, a Mixed Terpenoid Section 11.1: Lipid Classes

32. Steroids Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011  Exhibit feature of other lipids (e.g., soluble in non-polar solvents)  Cholesterol is most abundant steroid in human body  Essential component of cell membranes  Precursor for other steroids:  Bile salts  Sex hormones  Vitamin D  Adrenocorticoid hormones  Synthesized in liver or obtained from food  May contribute to atherosclerosis SteroidCholesterol

33.  Cholesterol is an important molecule in animal cells that is classified as a sterol, because C-3 is oxidized to a hydroxyl group  Essential in animal membranes; a precursor of all steroid hormones, vitamin D, and bile salts  Usually stored in cells as a fatty acid ester Section 11.1: Lipid Classes

34. Figure 11.19 Animal Steroids Section 11.1: Lipid Classes

35. Bile Salts Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011; http://www.medicinenet.com/gallstones/article.htm  Yellow-brown or green liver secretion stored in gallbladder  Bile salts are released into intestine to separate large globules of lipids into smaller droplets  Bile salts also emulsify (mix immiscibles) cholesterol found in the bile for excretion  Gallstones may occur if cholesterol too high and/or bile salts too low

36. Steroid Hormones http://schoolworkhelper.net/2010/07/the-endocrine-system-function-and-structure/  Hormone: Chemical produced in the cell or gland that delivers a message affecting cells in another part of the organism  Steroid hormones derived from cholesterol  Two Major Steroid Hormones:  Adrenocorticoid Hormones  Male and Female Sex Hormones  Steroid hormones diffuse through the cell membrane and combine with receptor proteins in the cytoplasm  Hormone-receptor complex cause cell to respond to hormone by interacting with cell DNA and stimulating protein synthesis

37. Adrenocorticoid Hormones Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011  Produced in adrenal glands located at top of kidneys  Classified into 2 functional groups:  Mineralocorticoids: Regulate concentration of ions (Na+) in body fluids  Aldosterone: most important mineralocorticoid  Promotes absorption of Na + and Cl - in kidney tubules  Glucorticoids: Enhance carbohydrate metabolism  Cortisol is major glucocorticoid in human body  Increases glucose and glycogen concentration in body  Cortisol, cortisone and prednisolone exert anti-inflammatory effects  Used to treat rheumatoid arthritis, bronchial asthma

38. Male Sex Hormones Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011; http://artofamandanelson.blogspot.com/2011/09/generating-topics- steroids.html  Male sex hormones (androgens) produced in testes  Testosterone: Most important  Promotes normal growth of male genitalia and aids in development of secondary sex characteristics  Anabolic steroids banned for use by athletes include testosterone and derivatives  Use of these can lead to:  Liver tumors  Testicular atrophy  Decreased sperm count

39. Female Sex Hormones Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011  Female sex hormones promote development of secondary sex characteristics  Increase in voice pitch  Increased breast size  Inhibition of facial hair  Estrogens:  Primary female sex hormones, play important roles in reproduction:  Estradiol  Estrone  Progesterone

40.  Lipoproteins  Transport lipid molecules through the bloodstream from organ to organ  Protein components (apolipoproteins) for lipoproteins are synthesized in the liver or intestine Figure 11.21 Plasma Lipoproteins Section 11.1: Lipid Classes

41.  Lipoproteins are classified according to their density:  Chylomicrons are large lipoproteins of extremely low density that transport triacylglycerol and cholesteryl esters (synthesized in the intestines)  Very low density lipoproteins (VLDL) are synthesized in the liver and transport lipids to the tissues  Low density lipoproteins (LDL) are principle transporters of cholesterol and cholesteryl esters to tissues  High density lipoprotein (HDL) is a protein-rich particle produced in the liver and intestine that seems to be a scavenger of excess cholesterol from membranes Section 11.1: Lipid Classes

42. Properties of Unsaturated Fatty Acids Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7 th Edition, 2011 Phospholipids form bilayer in cell membrane

43.  Membrane lipids: R esponsible for many membrane properties  Membrane fluidity refers to the viscosity of the lipid bilayer  Lipids may diffuse, or move around, within the membrane  Lipids may also flip from one side of the membrane to the other Figure 11.25 Lateral Diffusion in Biological Membranes Section 11.2: Membranes

44.  The movement of molecules from one side of a membrane to the other requires a flipase  Membrane fluidity largely depends on the percentage of unsaturated fatty acids and cholesterol  Cholesterol contributes to stability with its rigid ring system and fluidity with its flexible hydrocarbon tail Figure 11.24 Diagrammatic View of a Lipid Bilayer Section 11.2: Membranes

45. Membrane Properties:  Selective permeability is provided by the hydrophobic chains of the lipid bilayer, which is impermeable to most all molecules (except small nonpolar molecules)  Membrane proteins help regulate the movement of ionic and polar substances  Small nonpolar substances may diffuse down their concentration gradient  Self-sealing is a result of the lateral flow of lipid molecules after a small disruption  Asymmetry of biological membranes is necessary for their function  The lipid composition on each side of the membrane is different Section 11.2: Membranes

46.  Membrane Proteins—most functions associated with the membrane require membrane proteins  Classified by their relationship with the membrane: peripheral or integral Figure 11.26 Integral and Peripheral Membrane Proteins Section 11.2: Membranes

47.  Integral proteins embed in or pass through the membrane  Red blood cell anion exchanger  Peripheral proteins are bound to the membrane primarily through noncovalent interactions  Can be linked covalently through myristic, palmitic, or prenyl groups Figure 11.27 Red Blood Cell Integral Membrane Proteins Section 11.2: Membranes

48.  Membrane Microdomains—lipids and proteins in membranes are not uniformly distributed  Specialized microdomains like “lipid rafts” can be found in the external leaflet of the plasma membrane Figure 11.28 Lipid Rafts Section 11.2: Membranes

49.  Lipid rafts often include cholesterol, sphingolipids, and certain proteins  Lipid molecules are more ordered (less fluid) than non- raft regions  Lipid rafts have been implicated in a number of processes: exocytosis, endocytosis, and signal transduction Figure 11.29 The Lipid Raft Environment Section 11.2: Membranes

50.  Membrane Function  There are a vast array of membrane functions, including transport of polar and charged substances and the relay of signals Figure 11.30 Transport across Membranes Section 11.2: Membranes

51.  Membrane Transport  Ions and molecules constantly move across the plasma membrane and membranes of organelles  Important for nutrient intake, waste excretion, and the regulation of ion concentration  Biological transport mechanisms are classified according to whether they require energy Section 11.2: Membranes

52.  In passive transport, there is no energy input, while in active transport, energy is required  Passive is exemplified by simple diffusion and facilitated diffusion (with the concentration gradient)  Active transport uses energy to transport molecules against a concentration gradient Figure 11.30 Transport across Membranes Section 11.2: Membranes

53.  Simple diffusion involves the propulsion of each solute by random molecular motion from an area of high concentration to an area of low concentration  Diffusion of gases O 2 and CO 2 across membranes is proportional to their concentration gradients  Facilitated diffusion uses channel proteins to move large or charged molecules down their concentration gradient  Examples include chemically gated Na + channel and voltage-gated K + channel Section 11.2: Membranes

54.  Active transport has two forms: primary and secondary  In primary active transport, transmembrane ATP- hydrolyzing enzymes provide the energy to drive the transport of ions or molecules  Na + -K + ATPase Figure 11.31 The Na + -K + ATPase and Glucose Transport Section 11.2: Membranes

55.  In secondary active transport, concentration gradients formed by primary active transport are used to move other substances across the membrane  Na + -K + ATPase pump in the kidney drives the movement of D -glucose against its concentration gradient Figure 11.31 The Na + -K + ATPase and Glucose Transport Section 11.2: Membranes

56.  Membrane Receptors provide mechanisms by which cells monitor and respond to changes in their environment  Chemical signals bind to membrane receptors in multicellular organisms for intracellular communication  Other receptors are involved in cell-cell recognition  Binding of ligand to membrane receptor causes a conformational change and programmed response Section 11.2: Membranes