Lipid Chemistry - Biochemistry Simplified

Lipids are a diverse group of organic compounds that are insoluble in water but soluble in organic solvents like alcohol and chloroform. They serve as major energy reserves, membrane components, hormones, and insulators. Based on Bloor’s classification, lipids are of three types: simple, compound, and derived. Simple lipids are esters of fatty acids with alcohols—fats and oils (with glycerol) and waxes (with higher alcohols). Compound lipids contain additional groups such as phosphate, carbohydrates, or proteins; these include phospholipids (lecithin, cephalin, sphingomyelin) essential for membranes and surfactants, and glycolipids (cerebrosides, gangliosides) vital in nervous tissue and as blood group determinants. Derived lipids like fatty acids, steroids, and prostaglandins originate from hydrolysis of other lipids. Fatty acids are aliphatic carboxylic acids that can be saturated (no double bonds) or unsaturated (mono- or polyunsaturated). Essential fatty acids (linoleic, α-linolenic, arachidonic) are polyunsaturated and must be obtained from diet; they maintain membrane integrity and synthesize eicosanoids, while deficiency causes skin lesions and reproductive issues. Triacylglycerols (neutral fats) are glycerol esters serving as major energy stores, thermal insulators, and shock absorbers. Phospholipids, with phosphate groups, are vital for membrane structure, lipid transport, and pulmonary surfactant synthesis—deficiency of which leads to respiratory distress syndrome in infants. Cholesterol, a 27-carbon sterol, forms cell membranes and is the precursor of bile acids, vitamin D, and steroid hormones. Lipoproteins transport lipids in plasma: chylomicrons (dietary TAGs), VLDL (TAGs from liver), LDL (cholesterol to tissues—“bad”), and HDL (cholesterol to liver—“good”). Lipid quality is assessed by the saponification and iodine numbers, indicating chain length and unsaturation respectively. Rancidity is fat spoilage from oxidation or hydrolysis, prevented by antioxidants like vitamin E. Amphipathic lipids possess both hydrophilic and hydrophobic regions, enabling micelle and membrane formation, while liposomes—phospholipid vesicles—are widely used in drug delivery, chemotherapy, and vaccine transport systems.

1. LIPID CHEMISTRY ESHWAR FACULTY OF MEDICINE YEN-KNU UNIVERSITY

2. Lipids : Lipids are defined as heterogeneous group of organic compounds, which are relatively insoluble in water and soluble in organic solvents. (alcohol, chloroform)

3. Amla – reduces total chol , LDL and TAG ´ S

4. Classification of lipids (Bloor’s classification) LIPIDS Simple lipids Compound lipids Derived lipids Fats/Oils waxes Phospholipids Glycolipids Other compound lipids 1. Glycerophospholipids 1. Cerebrosides 1. Lipoproteins 2. Spingophospholipids 2. Gangliosides 2. Amino lipids 3. Sulpho lipids

5. Simple lipids: simple lipids are esters of fatty acids with alcohol, they do not contain any conjugate group. Simple lipids are of two types based on alcohol present in them; Fats/oils Waxes

6. 1. Fats/oils: They are the esters of fatty acids with glycerol as alcohol. fats are solid at room temperature and oils are liquid E.g.: vegetable oils, fish liver oil, butter , ghee 2. Waxes: Waxes are esters of fatty acids with higher alcohols. ( monohydric long chain ) E.g.: bees wax, wool fat, spremaceti wax

7. Compound Lipids These lipids contain conjugate compounds in addition to fatty acids and alcohols, conjugate group can be a phosphate group, carbohydrates, proteins etc. Compounds lipids include phospholipids, glycolipids, sulpholipids, aminolipids.

8. 1. Phospholipids : the compound lipids containing phosphoric acid residues (phosphate group) in addition to fatty acids and alcohol. Phospholipids are of two types Phospholipids, containing phosphoric acid. Non-phosphorylated lipids

9. A. Phospholipids, containing phosphoric acid. Nitrogen containing glycerophospholipids; Lecithin – body uses lecithin for metabolic process and to move fats. Cephalin – growth and repair of nerve cells, skincare and treating bacterial infections. Phosphatidylserine – essential for normal immune function and apoptosis. 2. Non-nitrogen glycerophospholipids; Phosphatidylinositol – cell signalling and membrane protein function. Phosphatidylglycerol - cell signalling, cell membrane maintenance and photosynthesis in plants 3. Phosphosphingosides with sphingosine, sphingomyelin.

10. 2. Non-nitrogen glycerophospholipids; Phosphatidylinositol – cell signalling and membrane protein function. Phosphatidylglycerol - cell signalling, cell membrane maintenance and photosynthesis in plants 3. Phosphosphingosides with sphingosine, sphingomyelin.

11. B. Non-phosphorylated lipids Glycosphingolipids (carbohydrate) Cerebrosides Globosides Gangliosides

12. 2. Sulfolipids Sulfated cerebrosides Sulfated globosides Sulfated gangliosides

13. Derives lipids: Compounds which are derived from lipids or precursors of lipids are called derives lipids. Eg ; fatty acids, steroids, prostaglandins, leukotrienes etc Lipids composed with other compounds Proteolipids and lipoproteins

14. Biological importance of lipids Storage form of energy (triglycerides) Structural components of bio membranes Ast as surfactants, detergents and emulsifying agents Act as electric insulators in neurons

15. Provide insulation against changes in external temperature (subcutaneous fat) Protect internal organs by cushioning effect (pads of fat) Help in absorption of fat soluble vitamins Improve taste and palatability of food

16. FATTY ACIDS Fatty acids are included in the group of derived lipids and most common component of lipids in the body. Fatty acids are aliphatic carboxylic acids. General formula – R------CO------OH Where COOH represents the functional group.

17. Classification of fatty acids

18. Saturated fatty acids: they do not contain any double bond in their chain. Ex; acetic acid, propionic acid, valeric acid, palmitic acid , butyric acid etc,. Unsaturated fatty acids: they have double bond in their hydrocarbon chain. Ex; oleic acid, palmitoleic acid, linoleic acid etc,. They are subdivided into two groups based on number of double bonds present

19. Monounsaturated fatty acids – contain one double bond Ex; palmitoleic acid and oleic acid 2. Polyunsaturated fatty acids – contain more than one double bond Ex; Linoleic acid (2 double bonds), α -Linoleic acid (3 double bonds) Arachidonic acid (4 double bonds)

20. Omega – Series Fatty Acids (n-Series Fatty acids): Unsaturated fatty acids are designated as omega series fatty acids. There are 3 families of unsaturated fatty acids (based on bonding)

21. Omega 3-fatty acids ; first double bond is 3 carbons from CH3 end Ex; α -Linoleic acid, Timnodonic acid, Cervonic acid. 2. Omega 6-fatty acids ; first double bond is 6 carbons from CH3 end Ex; Linolic acid and Arachidonic acid 3. Omega 9-fatty acids ; first double bond is 9 carbons from CH3 end Ex; Oleic acid

22. Trans Fatty Acids: If the hydrogen atoms are on opposite sides of the double bond it is called trans fatty acids. Nearly all the naturally occurring fatty acids are in cis form.

23. Trans fatty acids are present in certain foods like beef, hydrogenated edible oils and dairy products. - Considered to be injurious to health. - Used in food industries, as they increase shelf life of fried food. - Trans fatty acids adversely effect multiple risk factors, including plasma lipids and lipoproteins, systemic inflammation, insulin resistance, diabetes.

24. Essential fatty acids: Fatty acids which Cannot be synthesised in the body, hence have to be supplied in the diet are called as EFA ´ S. Ex. Linoleic acid, α -Linoleic acid, Arachidonic acid. Note: all essential fatty acids are poly unsaturated fatty acid. Arachidonic acid can be synthesised by linoleic acid

25. Functions of Essential Fatty Acids Essential fatty acids serve as precursors of eicosanoids (prostaglandins, prostacyclin's, thromboxane's, leukotrienes, lipoxins)- local hormones Essential fatty acids helps in lipid transport Formation and function of cell membrane

26. 4. Lowering serum cholesterol – anti-atherogenic activity 5. Lipotropic effect- fat mobilization 6. Normal reproductive function- PUFA are important constituents of lipids of gonads 7. Normal epidermal growth

27. Deficiency manifestation: Deficiency of EFA in diet is associated with skin lesion (rough dry skin)- Phrynoderma (Toad skin) Characterised by- horny eruptions on the posterior and lateral parts of thigh and back and buttocks Deficiency of EFA also causes reproductive failure and fatty liver

28. Triacylglycerols (TAG) Triacylglycerols are also called as neutral fats and triglycerides (TG). Defined as esters of fatty acids with glycerol.

29. Composition : These are esters of the trihydric alcohol, glycerol with fatty acids. (1:3) Glycerol- A trihydric alcohol fatty acids- can be saturated, unsaturated, or both and can vary in length

30. Importance of TAG’S TAG’S, these are Stored form of lipids in adipose tissue but excess fat in body – obesity. (high energy and density) Naturally occurring oils and fats are mixtures of triglycerides. E.g. Triolein and Tripalmitin Cellular energy balance and lipid homeostasis Cell membrane components

31. Absorption of fat soluble vitamins, nutrients and other dietary and medical supplements Heart health- TG test helps understanding risk of heart disease, stroke and conditions involving arteries. Acts as heat insulators (subcutaneous fat) Acts as shock absorbents (fat filled pads)

32. Phospholipids (5 M) Phospholipids are the compound lipids containing phosphoric acid residues in addition to fatty acids and alcohol. Types : Depending upon the nature of alcohol present- 2 types Glycerophospholipids Spingophospholipids

33. Glycerophospholipids: They contain glycerol as alcohol. Ex; Lecithin (phosphatidyl choline), Cephalin-role in blood coagulation (phosphatidyl ethanolamine), plasmalogen, Cardiolipin(major PL seen in mitochondrial membrane in heart), Lung surfactant.

34. Functions of phospholipids: (3 M) The lung surfactant – prevents the collapsing of lungs. Participate in blood coagulation- a phospholipid called as platelet activating factor. Required for action of lipoprotein lipase and TAG lipase.

35. 4. Constituents of cell membrane- they maintain permeability of cell membrane (Lecithin) 5. Participate in lipid transport- required for formation of lipoprotein 6. Participate in eicosanoids synthesis.

36. Pulmonary surfactant: It is a surface active lipoprotein formed by alveolar cells This phosphoprotein has- hydrophobic and hydrophilic regions in same molecule Seen at- air water interface of alveoli Hydrophilic head dips in water and hydrophobic tail faces towards air, so that surface tension is reduced. Pulmonary surfactant reduces surface tension at air-liquid interface of alveoli, thus preventing its collapsing.

37. Deficiency manifestations: 1. Respiratory distress syndrome: Most common causes of morbidity in preterm neonates. Patients present shortly after birth with apnea , cyanosis, grunting inspiratory stridor, nasal flaring, poor feeding & tachypnea .

38. Radiological findings include- “ ground glass ” appearance. The preterm infant who has RDS has low amount of surfactant- due to defect in biosynthesis of DPL (dipalmitoyl lecithin) the main pulmonary surfactant Cause- immature lung cannot synthesise DPL .

39. NORMAL NEONATE LUNG GROUND GLASS APPERANVCE

40. L/S RATIO : Lecithin-to-sphingomyelin ratio, It is a test of amniotic fluid used to assess fetal lung maturity With a ratio of 2:1 or greater generally indicating mature lungs and a lower ratio suggesting immaturity R isk of developing RDS is >75%, if L/S ratio is <1.5

41. 2 . Acute Respiratory Distress Syndrome (ARDS) sever form of lung injury and syndrome of acute pulmonary inflammation. Characterised by sudden onset, impaired gas exchange, and pulmonary edema . Infection- most common cause of ARDS in children. (lung appear vulnerable in 1 st year of life) Cause ; Increased permeability of alveolar capillary barrier as a result of injury to endothelium, damage to alveolar cells leads to an influx of edema fluid into alveoli

42. Spingophospholipids They contain sphingosine as alcohol. Ex. Sphingomyelin. Sphingosine containing lipids may be of three types; Phosphosphingosides Glycosphingolipids Sulfatides

43. Phosphosphingosides : They contain phosphoric acid group A common Phosphosphingoside present abundantly in bio membranes, especially of the nervous system, is sphingomyelin- contains choline.

44. Sphingomyelin are the only sphingolipids that contain phosphate and have no sugar moiety. They can be found in large quantities in nervous system Different sphingolipid can be formed based on fatty acid attached.

45. Glycolipids Glycolipids are the compound lipids containing carbohydrate residues in addition to fatty acids and alcohol Types Cerebrosides Gangliosides

46. Cerebrosides: contain glucose or galactose as carbohydrate residues. Ex. Kerasin -intercellular adhesion, maintain cell structure Cerebron - blood lipid reduction, maintain cell structure Nervon- maintain healthy nervous system

47. Gangliosides These contain oligosaccharides and sialic acids as carbohydrate residues. Ex. GM1,GM2, GM3,GM4

48. Functions of glycolipids Major constituents of cell membrane, specially nervous tissue Present at outer layer of cell membrane and play cell to cell interaction, growth and development Blood group antigens are cell surface globosides, globosides present on RBC membranes are determinants of blood group A,B and O Gangliosides acts as hormone receptors

49. Cholesterol Cholesterol is a waxy, fat like substance that’s found in the blood and cells of the body. It is essential for good health and has many important functions. Structure All steroids have cyclopentanoperhydro phenanthrene ring system , it is fused ring system made up of 3 cyclohexane rings designated as A, B,C and D.

50. Cholesterol has a total of 27 carbon atoms one hydroxyl group at 3 rd position- characteristic of all sterols. There is a double bond between carbon atoms 5 and 6

51. Biological importance of cholesterol 1. Major structural component of cell membrane and plasma lipoproteins. 2. Precursor for the synthesis of all other steroids in the body. Ex. Steroid hormones, vitamin-D, bile acids. Name bile acids and bile salts

52. 3. Essential ingredient in the structure of lipoproteins. 4. Fatty acids are transported to liver as cholesteryl esters for oxidation 5. It is responsible for proper synthesis of neurotransmitters 6. It is used to insulate the nerve fibers 7. It metabolizes fat soluble vitamins

53. Excretion of cholesterol Average diet contains 300mg of cholesterol per day Body can synthesis 700mg per day Out of this 1000mg of cholesterol 500mg is excreted through bile, which is partly reabsorbed from intestine.

54. About 500mg of cholesterol is converted to bile acids which are excreted in the bile as bile salts. The unabsorbed part is acted upon by intestinal bacteria to from cholestanol and coprostanol - which are excreted in feces.

55. Lipoproteins (5 M) Since lipids are insoluble in water, they need the help of carriers in plasma. Hence they are complexed with proteins to form lipoproteins. The protein part of lipoprotein is called apolipoprotein

56. Classification of lipoproteins Depending on the density or on the electrophoretic mobility, the lipoproteins in plasma are classified- 5 major types

57. Chylomicrons: Contains apoprotein B-48 Function : Chylomicrons are transfer form of dietary triglycerides from intestine to the adipose tissue for storage and to muscle or heart for their energy needs.

58. 2. Very low density lipoprotein (VLDL): Also called pre-beta lipoprotein. Contains apoprotein B-100 Function : Very low density lipoprotein carries triglycerides from liver to peripheral tissues for energy needs

59. 3. Intermediate density lipoprotein (IDL) Also called broad beta lipoprotein 4. Low density lipoprotein: (LDL) Most of the LDL particles are derived from VLDL Half life- 2 days

60. Also called beta lipoprotein, contains apoprotein B-100 Function : it is used for steroid hormone synthesis transport the cholesterol from liver to extra hepatic tissues. About 75% of plasma cholesterol is incorporated into the LDL particles

61. 5. High density lipoprotein (HDL) Also called alpha lipoprotein, contain apoprotein A1, with some apo A2 Function : transports cholesterol from peripheral tissues to heart. Anti-atherogenic effect

62. Free fatty acids: (FFA) Non esterified fatty acids which are complexed with albumin

63. Saponification number: It is defined as the number of milligrams of potassium hydroxide required to saponify 1g of fat. It’s a measure of average length of fatty acids in a fat or oil sample Iodine number: Iodine number of fat is defined as the number of grams of iodine taken up by 100g of fat.

64. Iodine number is also known as it is a mean of degree of unsaturation in fats, oils and waxes Iodine number is the amount of iodine reacts with 100 grams of a substance. It indicates the number of double bonds in fatty acids present in the substance. The more double bonds, the higher the iodine number

65. Rancidity: The term rancidity refers to the appearance of an unpleasant smell and taste for fats and oils Fats and oils tend to become rancid. Hydrolytic rancidity : due to partial hydrolysis of triacylglycerol molecules due to traces of hydrolytic enzymes presence in naturally occurring fats and oils

66. Oxidative rancidity : due to partial oxidation of unsaturated fatty acids wit6h resultant formation of epoxides and peroxides of small molecular weight fatty acids by free radicals. Vitamin E can prevent oxidative rancidity.

67. Amphipathic lipids Amphipathic lipids are the fats that have both polar and non-polar regions, molecule with hydrophilic heads and hydrophobic tails. Ex. Soap, detergents, oils and fats, phospholipids, cholesterol etc, These lipids are soluble in both polar and nonpolar solvents.

68. The hydrophilic part is ionic hence dissolves in water and hydrophobic part is hydrocarbon which dissolves in nonpolar substances When the amphipathic lipids are mixed in water, polar group orients towards aqueous phase while non polar group towards opposite direction- micelles formation micelles formation, facilitated by bile salts is very important for lipid digestion and absorption

69. Importance of amphipathic lipids Cell membrane formation- main components, made up of lipid bilayers. Transport of molecules- like sugars and amino acids across cell membrane. Stabilization of molecules- stabilize molecules like toxins and antibiotics within in cell membrane..

70. 4. Cell signalling 5. Immune response- amphipathic antimicrobial peptides have antibacterial and antifungal properties. 6. Digestion- amphipathic molecules are used in the body for digestion.

71. Liposomes Liposomes are the sphere shaped vesicles consisting of one or more phospholipid bilayers. A lipid bilayer will close on itself under appropriate conditions to form liposomes. They may be prepared by sonication of mixtures of phospholipids and cholesterol.