1. Lipid Chemistry Dr. S.Chakravarty MD

2. Specific Learning objectives: At the end of this session the student should be able to :- List the various lipases acting on triglycerides in different parts of the body List the components of Phospholipids and Glycolipids Describe the properties of Omega 3 and omega 6 fatty acids Describe the Functions of phospholipase A2 and C Classify the types of Phospholipids and Glycolipids Analyse the Composition of surfactant and its importance Describe the Sphingolipid metabolism and the enzyme deficient in various sphingolipidoses

3. Functions of lipids: Important form of energy storage (9.1 kcal/g) 30% daily energy requirements of the body Phospholipids are components of Biomembrane Major regulatory hormones – Steroids Storage and absorption of FAT soluble vitamins – A,D,E,K. Act as second messengers – Diacyl glycerol.

4. Cont.. Non polar lipids – myelin sheath – electrical insulator Inflammatory mediators – Eicosanoids Thermal insulators Lipoproteins – transport proteins Pathogenesis of DM, obesity, atherosclerosis TASTE – palatability of food

5. Lipids Source of energy Protection Thermal & Electrical insulator insulator Hormones Prostaglandins Lipoproteins Bile salts Vitamins

6. OBESITY  metabolic syndrome diabetes mellitus atherosclerosis

7. Classification of Lipids SIMPLE LIPIDS Derived Lipids COMPLEX(COMPOUND)LIPIDS LIPIDSLIPIDS

8. Classification : modified from Bloor 1.Simple lipids : Esters of fatty acids with various alcohols. a. Neutral Fats: Esters of fatty acids with glycerol. uncharged. Eg.- triolein, tripalmitin. Diet - triglycerides. Oils - Fats in the liquid state. Eg.- corn, groundnut oil. b. Waxes: Esters of fatty acids(c14 – 36) with higher M.wt monohydric long chain alcohols.( c16 - 30). Eg. Bees wax, lanolin, spermaceti oil. Used for lotions, ointments

9. CH 3 (CH 2 ) 14 C =OO CH 2 (CH 2 ) 28 CH 3 Palmitic acid 1-Triacontanol Triacontanoylpalmitate, the major component of beeswax.

10. Esters of fatty acids with alcohol + containing additional groups (prosthetic group). a. Phospholipids : Fatty acids,alcohol and a phosphate group, nitrogen containing bases and other substituents. eg, Glycerophospholipids the alcohol is glycerol Sphingophospholipids the alcohol is sphingosine. b. Glycolipids (glycosphingolipids) : fatty acid, sphingosine and carbohydrate with nitrogen base. c. Other complex lipids: Lipoproteins, sulfolipids and aminolipids. II)Complex Lipids :

11. Derived from simple lipids or complex lipids on hydrolysis. A)fatty acids, glycerol,Monoacyl and Diacylglycerol. B) Steroids- lipids with cyclo pentano perhydro phenanthrene (steroid) ring. Eg. – cholesterol and its derivatives- bile acids, hormones, Ergosterol. C)Eicosanoids – Arachidonic acid derivatives- PG,TXA 2, LTB. D) Terpenes – Isoprene units – 5 Carbon compound Eg.- Carotenes, vitamins A,E,K and Dolichol, CO-Q, Squalene. III) Precursor and Derived lipids :

12. IV) Others : Fatty aldehydes, ketone bodies, hydrocarbons and other alcohols.

13. Triglycerides : Storage form of fat in the adipose tissue. Synthesized mainly in liver, adipose tissue and lactating mammary. Acted upon by lipases: 1.Pancreatic 2.Lipoprotein – endothelium close to organs 3.Hormone sensitive – Adipose tissue 4.Hepatic - liver Neutral lipids - uncharged. Eg. acylglycerols, cholesterol, and cholesteryl esters.

14. Structure of fatty acid : Aliphatic unbranched Monocarboxylic acids: Methyl end or omega carbon Carboxylic acid end

15. Nomenclature of fatty acids: Nomenclature: 1.Delta (∆) naming: carbon ∆1 is carboxyl, ∆ 2 is called α carbon, ∆ 3 is  carbon, etc.  carbon numbering - terminal methyl group is always the omega carbon one. Number in the bracket is first double bond from omega i.e. 

17. Fatty acids: Bound with albumin in blood circulation – FFA ( NEVER FREE!!) Saturated – no double bonds – mostly solids Unsaturated – double bonds – mostly liquids PUFA – Essential fatty acids. Orientation around double bonds – cis and trans

18. Classification of fatty acids based on chain length: Short-chain fatty acids - Fewer than six carbons Medium-chain fatty acids (MCFA) - 6–12 c Long-chain fatty acids (LCFA) longer than 12 c Very-Long-chain fatty acids (VLCFA) longer than 20 c Eicosanoids –Derived and modified from 20 c Arachidonic acid.

19. ClASSIFICATION On the basis of no. of `C` atoms – even, odd Even number- e.g.-Palmitic acid / hexadecanoic acid, stearic acid. Odd number –e.g.-Propionic acid, Valeric acid e.g.-Propionic acid – C 2 H 5 COOH

20. Trans fat- HARMFUL Theory :-Trans fat not broken by LIPASE- Body can’t metabolize it. Deposition in the blood vessels. Partial hydrogenation of unsaturated oils – leads to trans fats. Free radical generation.

21. Essential fatty acids: ω-3 fatty acids: α-Linolenic acid (18:3) 9, 12, 15 ω-6 fatty acids: Linoleic acid (18:2)9,12 Why essential? Lack the ability to introduce double bonds in fatty acids beyond carbon ∆ 9 and 10. Δ 9 desaturase, Δ 6 desaturase, Δ 5 desaturase, and Δ 4 desaturase are present in the body.

22. Omega 3 fatty acid Omega 6 fatty acid Omega 9 fatty acid Saturated fatty acid 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

23. These EFA can be synthesized by chain elongation of linoleic and linolenic acid. ω-3 fatty acids: α-Linolenic acid Eicosapentaenoic acid or EPA (20:5) Docosahexaenoic acid or DHA (22:6) ω-6 fatty acids: Linoleic acid Gamma-linolenic acid or GLA (18:3) Arachidonic acid or AA (20:4) ω-9 fatty acids are not essential in humans, because humans generally possess all the enzymes required for their synthesis

24. Phospholipids: Derivative of phosphatidic acid. Types – glycerol / sphingol as alcohol. Chief component of plasma membrane. Forms micelles- polarity. Phosphate (hydrophilic) Glycerol Fatty acid (hydrophobic)

25. Phospholipases: on Membrane phospholipids CH2 CH CH2 Saturated fatty acid (Palmitic acid) Unsaturated fatty acid (Arachidonic acid) PO4 F1 F2 Inositol PO4 1 2 3 A1 A2 CD B Phosphatidyl Inositol 4,5 Bisphosphate

26. Phospholipases: Phospholipase A : Phospholipase A1 - cleaves the SN-1 acyl chain Phospholipase A2 - cleaves the SN-2 acyl chain releasing Arachidonic acid Phospholipase B - cleaves both SN-1 and SN-2 acyl chains, also known as a lysophospholipase Phospholipase C - cleaves before the phosphate, releasing Diacyl glycerol and Inositol triphosphate Phospholipase D - cleaves after phosphate, releasing phosphatidic acid.

27. Dipalmitoyl lecithin : Dipalmitoyl phosphatidyl choline – acts as a surfactant in lungs Reduces surface tension of alveoli Absence – respiratory distress syndrome. Mainly seen with preterm infants born before 32 wks gestation.

28. Sphingomyelin: Ceramide = Fatty acid + Sphingosine (alcohol) Present in brain and nervous tissues.

29. Cholesterol :Very Important for Body Cell membrane Synthesis of steroid hormones Synthesis of vitamin D Synthesis of bile salts Cyclopentanoperhydrophenanthrene ring

30. Glycolipids Ceramide + carbohydrate moiety Ceramide = Fatty acid + Sphingosine (alcohol) Present in central and peripheral nervous system and as cell surface antigens on plasma membrane. Cerebrosides – Ceramide +Galactose/Glucose Gangliosides – Cerebrosides + Sialic acid (9 carbon sugar – NANA). Fatty acid is usually Cerebronic acid.

31. Gangliosides – clinical importance Haemagglutinin of Influenza virus exploits certain gangliosides to enter and infect the cells expressing them. Tay-Sachs Disease involves accumulation of GM 2 gangliosides due to def of hexosaminidase. Guillain-Barré syndrome- anti ganglioside antibody. Cholera toxin – acts through GM1 ganglioside.

32. Thank you