LIPIDS AND MEMBRANES December 2016 B.pptx

notes about lipids in biochemistry

1. LIPIDS AND MEMBRANES 2016/17 ACADEMIC

2. Lipid A naturally occurring molecule which is soluble in nonpolar organic solvents. Lipids are very diverse in structure Lipid molecules include: Fats and oils Waxes Sterols Phospholipids Etc

3. Two commonest lipid molecules are: Fats Oils Fats are solid at room temperature (25°C). A mixture of triacylglycerols that is solid because it contains a high proportion of saturated fatty acids.

4. •Oils are liquid at room temperature (25°C). A mixture of triacylglycerols that is liquid because it contains a high proportion of unsaturated fatty acids. Triacylglycerols in natural fats and oils are nonpolar , hydrophobic molecules with no ionic charges.

5. Structure of Fat/Oil Molecule There are two main components of fats/oils: Glycerol Fatty acid

6. Glycerol It is a trihydroxy alcohol

7. Fatty Acids These are mostly long chain carboxylic acids (>10 C). Naturally occurring fatty acids have even number of carbon atoms. Very often referred by their common names which indicates their source. Examples Lauric acid- dodecanoic acid (12 carbons). CH 3 (CH 2 ) 10 COOH Myristic acid- tetradecanoic acid (14 carbons). CH 3 (CH 2 ) 12 COOH

8. Palmitic acid- hexadecanoic acid (16 carbons). CH 3 (CH 2 ) 14 COOH Stearic acid- octadecanoic acid (18 carbons). CH 3 (CH 2 ) 16 COOH Arachidonic acid- eicosanoic acid (20 carbons). CH 3 (CH 2 ) 18 COOH

9. Saturated and Unsaturated fatty acids The fatty acid molecule in the lipid can either be saturated or unsaturated. Saturated fatty acid: A long-chain carboxylic acid containing only carbon–carbon single bonds. Saturated fatty acids of 12 - 20 C are common; overall shape = straight

10. Unsaturated fatty acid: A long-chain carboxylic acid containing one or more carbon–carbon double bonds. Unsaturated fatty acids in nature are always cis isomers. puts a “kink” in the chains & affects 3-D structure (trans-fatty acids only formed synthetically)

11. Polyunsaturated fatty acids have more than one C=C double bond. As the number of double bonds increases (polyunsaturated) melting points decrease

12. Linoleic and linolenic acids are essential in the human diet because the body does not synthesize them. They are needed for the synthesis of other lipids.

13. TRIGLYCERIDES Triacylglycerols are carboxylic acid triesters of glycerol, a three-carbon trialcohol and three fatty acids. They make up the fats stored in our bodies and most dietary fats and oils. They are a major source of biochemical energy.

14. Animal fats and vegetable oils are the most plentiful lipids in nature. All fats and oils are composed of triesters of glycerol (1,2,3-propanetriol, also known as glycerine ) with three fatty acids. They are named chemically as triacylglycerols , but are often called triglycerides.

15. Fatty acid on carbon 1 is typically saturated. Fatty acid on carbon 2 is typically unsaturated. Fatty acid on carbon 3 can be either saturated or unsaturated. The three fatty acids esterified to glycerol usually are not the same type.

16. Some key points about structure and properties of triacylglycerols . 1) TAG that are solid at room temperature are classified as fats (animal-based ). 2) TAG that are liquid at room temp. are classified as oils (vegetable-based ). 3) In general, the more unsaturated the fatty acids in a TAG, the less solid it is.

17. 4) Most liquid TAG come from plant sources (olives, corn, safflower). 5) Most solid or primarily saturated fats come from animal sources. 6) 3-D structure of fatty acids affects packing which in turn affects melting point. Trans fatty acid is similar in shape to a saturated fatty acid. Unsaturated TAG do not pack as tightly due to shape

18. Fatty acids are a major component of: Lipoproteins especially LDL (low-density lipoproteins) Cell membranes. Oxidation degrades membranes and makes them less fluid.

19. Oxidation of fatty acids causes “rancidity” - oxidative cleavage of unsaturated fatty acids leading to shorter chain aldehydes and acids. Antioxidants can protect the unsaturated fatty acids. These are compounds which react with free radicals (often by forming a more stable free radical) and remove them from the site before damage occurs. Packaging (air tight) also is used to reduce rancidity of fats

20. Hydrogenation of unsaturated fatty acids Unsaturated fatty acids may be converted to saturated fatty acids by the relatively simple hydrogenation reaction. Recall that the addition of hydrogen to an alkene (unsaturated) results in an alkane (saturated). A simple hydrogenation reaction is: Ni/ atm H 2 C=CH 2  + H 2  ---> CH 3 CH 3 alkene plus hydrogen yields an alkane

21. Vegetable oils are commonly referred to as "polyunsaturated". This simply means that there are several double bonds present. Vegetable oils may be converted from liquids to solids by the hydrogenation reaction. An important industrial process is the manufacture of margarines and shortenings. Margarines and shortenings are "hardened" in this way to make them solid or semi-solids.

22. Saponification Reaction of lipids with strong bases such as NaOH to form a soap. Hydrolysis Breakdown of the triglyceride molecule to produce glycerol and the fatty acids. Transesterification ?

23. Mono-and DI- glycerides Diglycerides are formed when only two fatty acid molecules are esterified to the glycerol molecule. 1,2-diglyceride 1,3-diglyceride

24. Monoglycerides are formed when only one fatty acid molecule is esterified to the glycerol. 1-monoglyceride 2-monoglyceride

25. Phospholipids, sphingolipids and the structure of cell membranes

26. Phospholipids are a major component of all cell membranes as they can form lipid bilayers . Most phospholipids contain a  diglyceride , a phosphate group, and a simple organic molecule such as choline . The first phospholipid identified as such in biological tissues was lecithin, or  phosphatidylcholine , in the egg. The structure of the phospholipid molecule generally consists of hydrophobic tails and a hydrophilic head.

27. Phosphatidyl choline (PC)

28. Phosphatidylserine (PS)

29. In general, phospholipids are composed of a phosphate group, two alcohols, and one or two fatty acids . On one end of the molecule are the phosphate group and one alcohol; this end is polar,  i.e.,  has an electric charge, and is attracted to  water (hydrophilic). The other end, which consists of the fatty acids, is neutral; it is hydrophobic and water-insoluble but is fat-soluble. This amphipathic nature (containing both hydrophobic and hydrophilic groups) makes phospholipids important in membranes. They form a two-layer structure, called the  lipid   bilayer , with the polar head facing out on each surface to interact with water, and with the neutral “tails” driven inward and pointing toward one another.

30. The lipid bilayer is the structural basis of all cell membranes and is nearly impermeable to ions and most polar molecules. The major role is as a barrier between cells and their environment. Thus separating the cytoplasm and cellular structures from the extracellular fluid and each other . Proteins embedded in the phospholipid matrix transport many substances through the membrane.

31. Sphingolipids

32. Sphingosine is the alcohol instead of glycerol NOTE that an amino group replaces an OH group in sphingosine

33. The sphingolipids comprise a complex range of lipids in which fatty acids are linked via amide bonds to a long-chain base or sphingoid . sphingolipids are extremely versatile molecules. Found in nerve tissue. They are also found in a few bacterial genera (but especially  Sphingomonas  and  Sphingobacterium ).

34. A  long-chain base , such as sphingosine , is the simplest possible functional sphingolipid Ceramides which contain a fatty acid linked by an amide bond, are also the precursors of phospholipids and glycolipids Sphingomyelin  has structural similarities to phosphatidylcholine , but has very different physical and biological properties Oligoglycosylceramides  and  gangliosides .   These are Complex sphingolipids located mainly in the plasma membrane of mammalian cells where they have a structural function, and also serve as adhesion sites for proteins from the extracellular tissue. Sphingolipids and their metabolites have important roles in signal transduction.

35. STEROIDS ISOPRENOIDS

36. Steroids form an important group of compounds based on the fused four saturated carbon rings 1,2-cyclopentanoperhydrophenanthrene ( sterane ).

37. Steroids comprise a group of cyclic organic compounds. The most common characteristic is an arrangement of seventeen carbon atoms in a four-ring structure. There are three rings composed of 6-carbons (rings A, B, and C) followed by one with 5-carbons (ring D). They have an 8-carbon side chain attached to a carbon on ring D, and two or more methyl groups at the points where adjacent rings are  "fused" . 

38. Cholesterol

39. Progesterone Lanosterol Bile acid Testosterone Estrogen

40. KEY POINTS Steroids  are lipids because they are hydrophobic and insoluble in water, but they do not resemble lipids since they have a structure composed of four fused rings. Cholesterol is the most common steroid and is the precursor to  vitamin  D,  testosterone ,  estrogen , progesterone,  aldosterone , cortisol , and bile salts. Cholesterol is a component of the phospholipid   bilayer and plays a role in the structure and function of membranes.

41. Steroids are found in the brain and alter electrical activity in the brain. Because they can tone down  receptors  that communicate messages from  neurotransmitters , steroids are often used in anesthetic medicines.

42. WAXES Waxes are a class ofchemical compounds that are plastic (malleable) near ambient temperatures. They melt above 45 °C (113 °F) to give a low viscosity liquid. Waxes are insoluble in water but soluble in organic, nonpolar solvents. All waxes are organic compounds, both synthetic and natural

43. Plant and Animal Waxes Waxes are  synthesized  by many plants and animals. Those of animal origin consist of wax esters derived from a variety of carboxylic acids  and  fatty alcohols . Waxes of plant origin are mainly unesterified hydrocarbons.  The composition depends not only on species, but also on geographic location of the organism. Because they are mixtures, naturally produced waxes are softer and melt at lower temperatures than the pure components.

44. Animal waxes The most commonly known animal wax is  beeswax , A major component of the beeswax used in constructing  honeycombs  is the  ester   myricyl palmitate which is an ester of  triacontanol  and  palmitic acid . Its melting point is 62-65 °C.   Lanolin  is a wax obtained from wool, consisting of esters of  sterols .

45. Table 3. Relative composition (wt % of the total) of the non-polar lipids from the skin surface of various species. Squalene Sterols Sterol esters Wax esters Diesters Glyceryl ethers Triacyl- glycerols Free acids Free alcohols   Human 12 1 3 25 41 16   Sheep 12 46 10 21 11   Rat 1 6 27 17 21 8 1   Mouse 13 10 5 65 6 Adapted from Downing, D.T.  Mammalian waxes . In:  Chemistry and Biochemistry of Natural Waxes . (Ed. P.E. Kolattukudy , Elsevier, Amsterdam) (1976).

46. Plant waxes Plants secrete waxes into and on the surface of their cuticles as a way to control evaporation, wettability and hydration. The  epicuticular waxes  of plants are mixtures of substituted long-chain  aliphatic   hydrocarbons , containing  alkanes , alkyl esters, fatty acids, primary and  secondary alcohols diols ketones aldehydes .

47. Commercially the most important plant wax is  Carnauba wax , a hard wax obtained from the Brazilian palm  Copernicia prunifera . It contains the ester myricyl cerotate and has many applications, such as confectionery and other food coatings, car and furniture polish, floss coating and other uses.

48. Table 1. The major constituents of plant leaf waxes.   n- Alkanes CH 3 (CH 2 ) x CH 3 21 to 35C - odd numbered   Alkyl esters CH 3 (CH 2 ) x COO (CH 2 ) y CH 3 34 to 62C - even numbered   Fatty acids CH 3 (CH 2 ) x COOH 16 to 32C - even numbered   Fatty alcohols (primary) CH 3 (CH 2 ) y CH 2 OH 22 to 32C - even numbered   Fatty aldehydes CH 3 (CH 2 ) y CHO 22 to 32C - even numbered   Ketones CH 3 (CH 2 ) x CO (CH 2 ) y CH 3 23 to 33C - odd numbered   Fatty alcohols (secondary) CH 3 (CH 2 ) x CHOH (CH 2 ) y CH 3 23 to 33C - odd numbered   β- Diketones CH 3 (CH 2 ) x COCH 2 CO(CH 2 ) y CH 3 27 to 33C - odd numbered   Triterpenols Sterols, α- amyrin , β- amyrin , uvaol , lupeol , erythrodiol   Triterpenoid acids Ursolic acid, oleanolic acid, etc

49. Table 2. Relative proportions (wt %) of the common wax constituents in some plant species. Arabidopsis leaf Rape leaf Apple fruit Rose flower Pea leaf Sugar cane stem   Hydrocarbons 73 33 20 58 40-50 2-8   Wax esters - 16 18 11 5-10 6    Aldehydes 14 3 2 - 5 50    Ketones 4 20 3 - -   Secondary     alcohols 1 8 20 9 7 -   Primary alcohols 8 12 6 4 20 5-25   Acids 1 8 20 5 6 3-8 Other components present include various diol types and triterpenoid acids

50. BIOLOGICAL MEMBRANES Biological membranes or  biomembranes are enclosing or separating membranes that act as selectively permeable  barriers within living cells. They consist of a phospholipid bilayer  with embedded integral  and  peripheral protein. The proteins are used in communication and transportation of chemicals and ions.

51. Functions of Biological Membranes Active transport of K + ,Na + ,Ca 2+ , maintaining the osmotic equilibrium in all cells ( cytoplasmic ) Binding of hormones and switching on of mechanisms of intracellular signaling in majority of cells. Generation of action potential by nerve and muscle cells.

52. Transfer of electrons on to oxygen and synthesis of ATP (oxidative phosphorylation ) by majority of cells in Inner membrane of mitochondria. Transfer of Ca 2+ from cell solutions into vesicles in majority of cells. Absorption of light quanta and generation of intracellular signal by eye epithelium cells.

53. MEMBRANE STRUCTURE The phospholipids within the membrane are amphipathic in nature Polar heads favour contact with water Hydrocarbon tails interact with one another in the middle The preferred structure for most phospholipids and glycolipids in aqueous media is a bimolecular sheet (lipid bilayer)

54. Lipid Bilayer

55. Cell Membrane Asymmetry The cell membranes tend to have different composition on one side of the membrane than on the other. The differences can be caused by the different ratios or types of amphipathic lipid-based molecules, the different positioning of the proteins (facing in or facing out), or the fixed orientations of proteins spanning the membrane. In addition, there are different enzymatic activities in the outer and inner membrane surfaces. The reason the cell membrane is asymmetric is because when the proteins are synthesized by the preexisting membranes, they are inserted into the membrane in an asymmetric manner. The cell membrane's phospholipids are distributed asymmetrically across the lipid bilayer , in a phenomenon called membrane phospholipid asymmetry.

56. Signal for destruction membrane asymmetry

57. Protein Targeting   Protein targeting  or  protein sorting  is the biological mechanism by which  proteins  are transported to the appropriate destinations in the cell or outside of it. Proteins can be targeted to the inner space of an  organelle , different intracellular membranes plasma membrane , or to exterior of the cell via  secretion . This delivery process is carried out based on information contained in the protein itself. Correct sorting is crucial for the cell; errors can lead to diseases.