1. CHAPTER 6 LIPIDS and MEMBRANES 1

2. WHAT IS LIPID ?? Are a diverse group of water-insoluble organic compounds. Lipid is soluble in nonpolar organic solvents such as  chloroform, ether and benzene Lipids can be hydrophobic (non-polar) or amphipathic (have both non- polar and polar regions). It contains a long chain hydrocarbon groups in their molecules. Lipids are among the major components of food of plant and animal origin. Lipids rarely exist in an organism in the free state but are usually associated with proteins or combined with polysaccharides. 2

3. THE IMPORTANCE OF LIPIDS Functions of lipids: important dietary constituents providing energy, vitamins and essential fatty acids and often give flavour and palatability to food. act as lubricants and insulators and the fat stores in the adipose tissue of the body are a rich source of energy. Combinations of lipids and protein are of particular cellular importance especially in membrane structures and also as a means of transporting lipids in the blood. The steroid hormones are derived from cholesterol and very small amounts of these exert potent physiological effect. SOME LIPIDS THAT NOT FOUND IN MEMBRANES… a) waxes, b) eicosanoids and c) some isoprenoids 3

4. The classification of lipid is based on : –its physical properties at room temperature (oils are liquid and fats are solid), –its polarity (polar and neutral lipids) and –its structural properties (simple, complex and derived lipids). OIL  generally obtained from plant sources  are liquid at room temperature  eg. coconut oil, groundnut oil, soybean oil cottonseed oil, corn oil and palm oil, FATS  generally of animal origin  are solid at room temperature  e.g. lard and tallow. CLASSIFICATION OF LIPIDS 4

5. Lipids have been classified in a variety of ways but generally two categories, simple and complex. simple or neutral lipids  are the largest group of lipids comprising of about 90 – 98% of the lipids. –include fatty acids, alcohols, glycerides and sterol, while polar lipids are the glycerophospholipids and glyceroglycolipids. –Structure lipids comprises of simple lipids which are compounds containing two types of structural moiety such as the glyceryl esters, cholesteryl esters, waxes and ceramides complex lipids  which are compounds with more than 2 types of structural moiety. –Examples of complex lipids include the phospholipids, glycoglycerolipids and sphingolipids. derived lipids  are lipids which involve fatty acids and alcohols (glycerol or sterol). Some examples of sterol include cholesterol and ergosterol CLASSIFICATION OF LIPIDS 5

6. STRUCTURAL RELATIONSHIPS OF THE MAJOR CLASSES OF LIPIDS LIPIDS 1.1 FATTY ACIDS 1.2 STEROIDS 1.3 LIPID VITAMINS 1.4 TERPENES 1.1.1 EICOSANOIDS 1.1.2 GLYCEROPHOSPHOLIPIDS 1.1.2.1 PLASMALOGENS 1.1.2.2 PHOSPHATIDES 1.1.2.2.1 PHOSPHOLIPIDS (5 types) 1.1.3 TRIACYLGLYCEROLS 1.1.4 WAXES 1.1.5 SPHINGOLIPIDS 1.1.5.1 CERAMIDES 1.1.5.1.1 GLYCOSPHINGOLIPIDS ISOPRENOIDS (structure related to 5 carbon molecule isoprene) 6

7. 1.1 FATTY ACIDS  Are carboxylic acid which differ in ;-  a) hydrocarbon chain  b) degree of unsaturation  c) position of double bond  Usually 4 – 36 carbon atoms (C 4 to C 36 ) in even numbered ONLY)  Named by  labeling the carboxylate group as (C1) OR carbon beside the carboxylate group as (α)  Saturated fatty acids  no double bond  Monounsaturated fatty acids  one double bond  Polyunsaturated fatty acids  more double bond > d.b = > mild (less viscous) 7

8. 1.1 FATTY ACIDS Fatty Acids saturated monounsaturated 8

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10. “ triacylglycerol or triglyceride” Fatty acids are generally stored as triacylglycerols (fats and oils) which are neutral and nonpolar. TAGs are esters of fatty acid and glycerol. formed from glycerol and fatty acids with the hydrogen (in all the –OH (hydroxyl) groups) in the glycerol molecule is replaced by fatty acid chains via the acid (carboxylic) end. simple triglycerides consist of 3 similar fatty acids, mixed triglycerides contain more than one type of fatty acid 1.1.3 TRIACYLGLYCEROLS (TAGs) Fatty acids can be obtained from triglycerides (fats/oil) through the process of fat splitting using high pressure and high temperature. It can also be performed using enzymes known as lipases. This reaction is reversible and therefore it is also used for the synthesis of esters from fatty acids and alcohol through the esterification reaction. 10

11. Basic composition of a triacylglyceride. The glycerol backbone is in blue Mixed TAG 11

12. a) Glycerol molecule;b) Monoglyceride;c) Diglyceride; d) Triglyceride 12

13. 1.1.3 TRIACYLGLYCEROLS (TAGs)  Basically…TAGs are fatty acids that stored as neutral lipids… a)Very hydrophobic b)Can be stored in anyhydrous form c)Fats and oils are mixtures of TAGs d)Can be solid (fats) or liquid (oils) at room temperature (25 o C)  Pancreatic lipases in the small intestines will digest TAGs 13

14. 1.1.2 GLYCEROPHOSPHOLIPIDS (GP) 1)TAGs can’t form structure of membrane hence it needs amphiphatic molecule 2)The most abundant is GP (a.k.a phosphoglycerides)  composed of… a glycerol backbone with 2 fatty acids groups attached to C1 and C2 of glycerol 3-phosphates Can be varied to form various GPs 3) Each GP  have same polar head BUT different fatty acyl chain 4) e.g. human red blood cell membrane 5) Generally, GPs have ;- a) saturated fatty acid at C1 b) unsaturated fatty acid at C2 14

15. 1.1.2 GLYCEROPHOSPHOLIPIDS (GP) 15

16. 1.1.2 GLYCEROPHOSPHOLIPIDS (GP) Polar heads (hydrophilics) Nonpolar tails (hydrophobics) 16

17. 1.1.5 SPHINGOLIPIDS 1)2 ND most abundant lipid in plant and animal membranes after glycerophospholipids (GP). 2)abundant in tissues of the cells 3)Contain a sphingosine backbone. Major classes of sphingolipids are: major families of sphingolipids sphingomyelinscerebrosidesgangliosides Present in plasma membrane of mammalian cells and myelin sheaths (surrounding nerve cells) Present in nerve tissues especially myelin sheath Present on cell surfaces 17

18. 1.1.5 SPHINGOLIPIDS 18

19. 1.2 STEROIDS 1)3 rd class of lipids 2)Found in membranes of eukaryotes 3)Derived from cholestrol Accumulate in lipid deposits (on the walls of blood vessels) This plaque implicated in cardiovascular diseases component of certain membranes Precursor of;- a)Steroid hormones b)Bile salts rigid fuse ring structures modulates the fluidity of membranes Transported as complexes as phospholipids 19

20. 1.2 STEROIDS 20

21. OTHER BIOLOGICALLY IMPORTANT LIPIDS Lipids that not found in membranes waxes eicosanoids terpenes 21 Lipid vitamins

22. LIPID BILAYERS AND MEMBRANE PROTEINS All biological membrane share some fundamental properties 22

23. 23 BIOLOGICAL MEMBRANES: COMPOSED OF LIPID BILAYERS & PROTEINS Lipid bilayers Main structural component of biological membranes, including plasma membrane & the internal membranes of eukaryotic cells. Consist of 2 monolayers (also known as sheets or leaflets). In each sheet, the polar head groups of amphipathic lipids are in contact of aqueous medium. The nonpolar hydrocarbon tails point towards the interior of the bilayer. Biological membranes = external boundaries of cells & separate compartments within cells. Consist of 2 layers of lipid molecules & many embedded proteins.

24. 24 Fluid Mosaic Model of Biological Membranes Biological membrane contains 25-50% lipid and 50-75% protein by mass, with less than 10% carbohydrate as a component in glycolipids & glycoproteins. The lipids are a complex mixture of phospholipids, glycosphingolipids (in animals) and cholesterol (in some eukaryotes). Cholestrol and other lipids that do not form bilayers by themselves (about 70%) are stabilised in a bilayer arrangement by the other 70& of lipids in the membrane. Compositions of biological membranes vary among different species and cell types. E.g.:  Inner mitochondrial membrane is rich in proteins due to its high level of metabolic activity.  Myelin membrane that insulates nerve fibers only has little protein.

25. 25 Myelin cells that insulates nerve fibers Source: http://images.emedicinehealth.com/images/44 53/4453-4464-63362-71453.jpg Inner membrane of mitochondrion Source: http://www.rpi.edu/dept/bcbp/molbiochem/MB Web/mb1/part2/oxphos.htm

26. 26 The fluid mosaic model proposed by S. Jonathan Singer & Garth L. Nicholson in 1972 describes the arrangement of lipid& protein within a membrane. According to this model, membrane is a dynamic structure where proteins & lipids can randomly diffuse laterally or rotate within the bilayer. Membrane proteins: There are 3 classes of membrane-bound proteins, divided based on their mode of attachment to the lipid bilayer. 1)Integral membrane proteins 2)Peripheral membrane proteins 3)Lipid-anchored membrane proteins.

27. 27 1)Integral membrane protein Aka transmembrane protein. One part of this protein is exposed on the outer surface while another part exposed on the inner surface of the bilayer. Are permanently bound to the membrane. E.g: bacteriorhodospin. An integral protein found in the cytoplasmic membrane of a halophilic (salt- loving) bacterium Halobacterium halobium. It helps harness light energy used in the synthesis of ATP.

28. 28 2) Peripheral membrane protein Attached to one of the surface of the membrane via charge-charge interactions or hydrogen bonding with integral proteins or with the polar head groups of membrane lipids. Easier to be removed without breaking covalent bonds or disrupting the membrane itself. A change o pH or ionic strength is enough to remove these proteins from the memrbane.

29. 29 3) Lipid-anchored membrane proteins Proteins that are covalently linked to the lipids in the bilayer known as lipid anchor. In the simplest lipid-anchored membrane proteins, an amino acid side chain is linked by an amide or ester bond to a fatty acyl group, usually from myristate or palmitate.

30. 30 3) Lipid-anchored membrane proteins (cont’d) The fatty acid is inserted into the cytoplasmic leaflet of the bilayer, anchoring the protein to the membrane. Most lipid-anchored proteins are permanently bound with the membrane although thee protein themselves do not interact with the membrane. Once released by treatment with phospholipases, the proteins behave like soluble proteins.

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