Exploring Lipids: Structures, Roles, and Properties

1. CHEM 3303.02 Biochemistry Chapter 10: Lipids

2. Knowledge/ skills Entire chapter- All except for most of Lipids as signals, cofactors and pigments • Storage lipids • Structural lipids in membranes • Vitamins A and D are hormone precursors • Vitamins E and K and the lipid quinones are oxidation/reduction cofactors

3. General information • Insoluble in water • Principal energy storage ( fats and oils) • Phospholipids and sterols are structural elements of biological membranes • Other as cofactors, electron carriers, light absorbing pigments, hydrophobic anchors for proteins • Chaperones for membrane folding • Emulsifying agents in digestion • Many lipids play a passive role for energy storage or as a barrier, some are active and play a role as messengers or signalling molecules such as hormones

4. Storage lipids • Fatty acids- • Complete oxidation to CO2 and H2O • Carboxylic acids with hydrocarbon chains ranging from 4-36 carbons • Chain can be branched/unbranched • Chain can be saturated/ unsaturated • May contain ring structures

5. naming • Simplified • Chain length:number of double bonds • Double bond position given by a Δ followed by the number of the carbon which is participating in the double bond. Note that the carboxyl group carbon is C-1 • E.g. 20:3(Δ3,9,12) denotes a carboxylic acid with 20 carbons and 3 double bonds between C-3 and C4; C-9 and C-10; C-12 and C-13 • Most commonly occurring have even numbers with unbranched chains- results from the fact that in biological systems the chains are put together from two Carbon (acetate) units

6. Many double bonds are Δ9, 12,15 in the cis configuration • Almost never see alternating single and double bonds but separated by a methylene group • Trans fatty acids produced by fermentation in diary animals and hydrogenation of fish or vegetable oils- these increase the levels of LDL or bad cholesterol and decrease the levels of HDL or good cholesterol

9. Physical properties – solubility in water • Largely determined by chain length and degree of saturation of the hydrocarbon chain • Longer fatty acyl chain- less soluble • Fewer double bonds- less soluble • Compare the solubility of lauric acid (12:0, Mr200) 0.063mg/ml vs glucose (Mr 180) 1,100 mg/ml • Carboxylic acid group is polar and ionized at pH7 and accounts for the slight solubility of the shorter chain fatty acids in water.

10. Physical properties- melting point • Influenced by length and degree of unsaturation of the hydrocarbon chain • At room temp the saturated fatty acids from 12:0 to 24:0 are waxy while the corresponding unsaturated fatty acids are oily liquids • Differences due to the degree of packing of the molecules • In fully saturated molecules, large degree of free rotation around the C-C backbone and very flexible and able to pack tightly into nearly crystalline arrays with atoms in contact all along their length • Unsaturated- cis double bond forces a kink in the hydrocarbon chain- result is that cannot pack as tightly as the fully saturated form. Overall van der Waal’s interactions less in unsaturated so less thermal energy to break bonds hence have lower melting points

12. In vertebrates, free fatty acids with a free carboxylate group are bound to a protein carrier called serum albumin • Fatty acid derivatives such as esters or amides lack the charged carboxylate group and are less soluble than free fatty acids.

13. Tri acyl glycerols • Composed of fatty acids linked to glycerol- by what linkage?

14. Ester linkage due to formation of a condensation bond Simple if all acids are the same, e.g. tristerin Most are mixed Polar groups of both glycerol and fatty acid are linked so triacylglycerols are nonpolar, hydrophobic and insoluble Lower specific gravity- float on water

15. Triacylglycerol function • Energy storage in adipocytes as fat droplets • Oils in plant seeds to provide energy and precursor molecules for germination • The carbon atoms of fatty acids are more reduced than carbohydrates so that more than twice the energy (gram for gram) is yielded • Because the molecule is hydrophobic, do not need water of hydration associated with polysaccharides (2g per gram of polysaccharide) • Carbohydrates are a quick energy source and are readily soluble in water • Fats are better for long term storage • Fats are good insulators against cold temperatures especially in animals that live in the cold or hibernate • Help with maintaining neutral buoyancy in diving animals like whales

16. There are 4 adipocytes in this picture • Can you tell where they are? • Storage lipids can make up more than 80% of the adipocyte dry cell mass

17. The sperm whale • Sperm whale’s head accounts for over 1/3 of its body weight. About 90% made up of spermaceti organ that is filled with spermaceti oil. The oil helps the animal maintain neutral buoyancy at ocean depths where it hunts its food and is able to change density depending on temperature

18. Saturation of oils • Many vegetable oils such as corn and olive oil are composed of triacylglycerols with unsaturated fatty acids- liquid at room temp • Hydrogenation reduces some double bonds to single bonds and can give trans double bonds • Exposure of lipids to air results in oxidative cleavage of double bonds to produce aldehydes and shorter chain carboxylic acids that are more volatile and smell rancid

20. Waxes • Esters of long chain (C14 to C36) saturated and unsaturated fatty acids with long chain alcohols • Melting points (60ºC – 100ºC) • Can be used as a metabolic fuel store • Provide water repellent properties- help to waterproof • Lubricate hair and skin • Protect against parasites • E.g. lanolin, beeswax, carnuba wax

22. Lipid types • This is an important overall picture of the lipids and how they are built

23. Lipids in membranes • Membranes serve as a barrier to passage of polar molecules and ions • The molecules are amphipathic, one end is hydrophobic and the other is hydrophilic • The hydrophilic end interact with water on either side of the membrane- can be a single OH or more complex as in the phospholipids, or sugars as in the glycolipids • The hydrophobic end interact with each other in a bilipid layer structure • Membrane lipids can make up 5 to 10% of the dry mass of cells

24. Glycerophospholipid • Aka phosphoglyceraldehydes • Two fatty acids attached via ester linkage to C-1 and C-2 of glycerol • Polar or charged group attached via a phosphodiester linkage to C-3 with an alcohol Di acyl-glycerol

25. Head group substituents

27. Ether lipids • Alkyl ether lipid- saturated • Plasmalogen- double bond between C-1 and C-2

28. An example of ester and ether linkage • Molecular signal to stimulate platelet aggregation

29. Galactolipids • One or two galactose residues connected by a glycosidic linkage to C-3 of a 1,2 diacylglycerol • Important in plant thylakoid membranes.

31. Sulfolipids • Sulfonate group bears a negative charge like a phosphate group

32. Glycerol dialkyl glycerol tetraether • Found in archaebacteria- live in extreme conditions of pH and temperature • Molecule is longer (32C) to make a membrane with a hydrophobic core and hydrophilic ends (glycerol) • Ether bond linkage more stable to hydrolysis than ester bond

33. Sphingolipids • Polar head group but use the long chain amino alcohol sphingosine instead of glycerol • Has one long chain fatty acid • Has a polar head group linked by a glycosidic linkage or phosphodiester linkage

37. Breakdown of membrane lipids • Membrane lipids continuously made/broken • Specific enzymes attack each hydrolyzable bond • Defects in these enzymes lead to severe consequences (Tay-Sachs)

38. Diseases associated with problems in breaking down sphingolipids

39. Sterols- e.g cholesterol • Have 4 fused Carbon rings, three 6 carbon and one 5 carbon to form the steroid nucleus- rigid and planar • Present in eukaryotic cells • Cholesterol is ampiphatic • Are precursors for steroid hormones which regulate gene expression

40. Examples of sex hormones

41. Vitamin A, D, E and K • Fat soluble vitamins • All are isoprenoid compounds synthesized by condensation of multiple isoprene units • Vitamin A and D are hormone precursors

42. 1,25-dihydroxycholecalciferol- a hormone that regulates calcium uptake in the intestine and Ca levels in kidney and bone; regulates gene expression to turn on synthesis of Ca 2+ binding protein

44. Vitamin A (retinol), hormone and visual pigment

45. Vitamin E- collective name for tocopherols • Contain a substituted aromatic ring and long isoprenoid side chain. • Are hydrophobic and associate with membranes, lipid deposits and lipoproteins • Aromatic ring destroys free radicals to protect fatty acids from being oxidized

46. Vitamin K • Undergoes oxidation and reduction during active prothrombin formation. • Prothrombin splits the peptide bonds in fibrinogen to fibrin an insoluble protein that holds blood clots together