Lipids of physiologic significance

Lipids of physiologic significance following the curriculum of Medical Biochemistry for MBBS course

1. Dr. Farhana Atia Assistant Professor Department of Biochemistry Nilphamari Medical College, Nilphamari Bangladesh Biomolecules: Lipids

2. Lipids Lipids are heterogeneous group of compounds that are related more by their physical than by their chemical properties They contain C, H, O ± P, N & S They have common properties of being Insoluble in water Soluble in nonpolar solvents as ether and benzene Associated with fatty acids and utilized by living organisms

3. Biomedical Importance Major source of energy for the body (High caloric value= 9.3 Kcal/g) Important dietary constituent, fat soluble vitamins & essential fatty acid are contained in the fat of natural food Fat is stored in adipose tissue Serve as thermal insulator in subcutaneous tissues & around certain organs Act as electrical insulator, allowing rapid propagation of depolarization waves along myelinated nerves Combination of lipid & protein (LP) serve as the means of transporting lipid in blood

4. Biomedical importance Provide hydrophobic barrier that permits partitioning of the aqueous contents of cells & subcutaneous structures Some fat soluble vitamins have regulatory or coenzyme function Prostaglandins & steroid hormones play a major roles in the control of the body’s homeostasis Have essential role in nutrition & health Imbalance of lipid metabolism may lead to some major clinical problems Atherosclerosis Obesity Diabetes Mellitus

5. Lipids: Classification 1. Simple lipid : Esters of FA with various alcohol Fat : Esters of FA with glycerol. [Oil- in liquid state] Waxes : Esters of FA with HMW monohydric alcohol 2. Complex lipid : Containing groups in addition to alcohol & FA (1) Phospholipids : Containing a phosphoric acid residue Glycerophospholipid [alcohol- glycerol] Sphingophospholipid [alcohol- sphigosine ] (2) Glycolipids ( glycosphingolipid ): Contain FA, Sphingosine & carbohydrate (3) Other : Sulpholipid , Aminolipid , Lipoproteins

6. Lipids: Classification 3. Derived lipid : Formed from hydrolysis of both simple and complex lipids. Fatty acid Glycerol Steroids Other alcohol Fatty aldehyde Ketone body Hydrocarbon Lipid soluble vitamins Hormones

7. Fatty acids (Aliphatic carboxylic acid) Long hydrocarbon chain with a polar carboxyl group at its end. Amphipathic molecule Polar / hydrophilic: COO⁻ Nonpolar / hydrophobic: Long HC chain Present in body Mainly as esters in natural fat & oils Unesterified / FFA [transported in plasma] Natural FA: usually even number of C atom (14-24)

8. Fatty acids: Nomenclature FAs are named after corresponding hydrocarbon Numbering of C atom From carboxyl carbon (no. 1) - 2, 3, 4  α , β , γ Terminal methyl carbon- ω / n Number & position of double bond ∆⁹: between 9/10 C ω 9: On 9 th counting from ω C 3 series of FA family: ω 9, ω 6, ω 3

9. Fatty Acids: Classification Saturated FA : No double bonds Palmitic acid (16C), Stearic acid (18C), Lauric acid (12C) Source: Animal & plant fat, coconut oil, butter, nutmeg, cinnamon, palm kernel, waxes Unsaturated FA : One or more double bonds Eicosanoids : Derived from eicosa ( 20-carbon) polyenoic fatty acid.

10. Unsaturated Fatty acids Monounsaturated FA: one double bond . Oleic acid (18:1;9) Source: nearly all fats, high in olive oil 2. Polyunsaturated FA (PUFA) : 2/more double bonds. Linoleic (18:2;9,2) α- Linolenic (18:3;9,12,15) Arachidonic (20:4;5,8,11,14) Cervonic (22:6;4,7,10,13,16,19) Source: Corn, peanut, cotton seed, soy bean, linseed oil , Fish oil (cod liver, salmon oil), phospholipids in brain

11. Fatty Acids: Classification Eicosanoids: Comprises- Prostanoides Prostaglandins/ PGs Prostacyclins / PGIs Thromboxanes / TXs Leukotreins / LTs Lipoxins / LXs PGs exist in all mammalian tissue Synthesized in vivo According to Chain length fatty acids are- Short chain FA: 2-10 carbon. Acetic acid (2C), butyric acid (4C) Long chain FA: >10 carbon. Palmitic (16C), stearic (18C)

12. Essential fatty acids Polyunsaturated fatty acids Human body is unable to synthesize Must be supplied in diet Linoleic acid , ω₆ FA , (  AA  Prostaglandins) α - Linolenic acid , ω₃ FA (Important for growth & development) Arachidonic acid , ( ω₆ FA), become essential if linoleic acid is absent in diet

13. Essential fatty acids Maintain fluidity of membrane structure Deficiency rare, occur in Infant on formula diet On IV nutrition exclusively for long time Result in Scaly dermatitis ( icthyosis ) Hair loss Visual abnormality Neurologic abnormality Poor wound healing

14. ω₆ /n₆ Family From vegetable oil: nuts, avocado, olive, soy bean, sesame, cotton seed, corn ↓plasma cholesterol ↓ LDL, also ↓HDL Excess intake (↑PUFA) oxidation of FA ↑free radicals Cancer Inflammatory Disease Atherosclerosis Aging ω₃ / n₃ Family From plants: linseed oil Fish oil (DHA & EPA) Have anti-inflammatory effect. So beneficial in cardiovascular disease Cancer Rheumatoid arthritis Alzheimer disease In infant- helps in brain development

15. Eicosanoids Prostaglandins & related compounds, thromboxanes & leukotriens are collectively known as eicosanoids Origin: PUFA with 20C Extremely potent compounds, elicit a wide range of responses Physiologic [inflammatory] Pathologic [hypersensitivity] Functionally compared to hormone, but Produce in small amount in all tissue Act locally Not stored, extremely short half life Action mediated by plasma mem . G protein coupled receptor

16. Synthesis of eicosanoids Diet (EFA) Linoleic acid Arachidonic acid Incorporated into membrane bound PL LXs PGE ₂

17. Functions of Eicosanoids PGF₂ α Produce by- most tissue Vasoconstriction Contraction of smooth muscle Uterine contraction PGE ₂ Produced-most tissue, kidney Vasodilatation Relax smooth muscle Used to induce labour PGI ₂ Produced in endothelium Vasodilatation Inhibit platelet aggregation TXA₂ Produced by platelets Promote platelet aggregation Vasoconstriction Mobilize IC calcium Contraction of smooth muscle

18. LTA₄ Produce- leukocytes, platelets, mast cell, heart & lung vascular tissue LTC₄/ LTD₄/ LTE₄ Contraction of smooth muscle Broncho -constriction Vasoconstriction ↑vascular permeability Make up slow reacting substances [SRS] of anaphylaxis Involved in pathophysiology of asthma LTB₄ ↑ chemotaxis of PMN leukocytes Release of lysosomal enzyme Adhesion of WBC LXs Anti-inflammatory role Immuno -regulatory function

19. Triacylglycerol Esters of trihydric alcohol and fatty acids Glycerol : Alcohol with 3 OH groups Main storage forms of fatty acids Thermal insulator

20. Phospholipids Esters of fatty acids, which contain an alcohol & one or more fatty acids and a phosphoric acid residue. They frequently have nitrogen containing bases (choline) & other substituents Glycerophospholipid [alcohol- glycerol] Sphingophospholipid [alcohol- sphigosine ]

21. Glycerophospholipids Sphingophospholipids Phosphatidylcholine (lecithin) Most abundant PL in membrane Acetylcholine Dipalmitoyl lecithin (surfactant) Phosphatidyl ethanolamine ( cephalin ) Phosphatidyl serine Phosphatidyl inositol (2 nd messenger) Plasmalogens (Brain, heart) Cardiolipins (mitochondria) Spingomyelins Component of cell membrane, nervous tissue and myelin sheath Play role in cell signaling & apoptosis Ceramide : combination of sphingosine plus fatty acid

22. Biomedical Importance of Phospholipids They are main lipid constituents of cell membrane Provide arachidonic acid for eicosanoids Surfactant- prevent adherence of inner surface of lung Play an important part in cell signaling & membrane trafficking Keep cholesterol in solution (in bile) Play role in apoptosis (programmed cell death) Acetylcholine is important in nervous transmission Cardiolipin - decrease level cause heart failure, hypothyroidism Plasmalogens may have a protective effect against reactive oxygen species

23. Glycolipids Glycosphingolipids Contain a fatty acid, sphingosine , and carbohydrate Widely distributed in every tissue (particularly in brain) Example: Cerebrosides , Gangliosides Biomedical Importance Component of biological membrane Present in brain, other nervous tissue & myelin Cell surface receptor ( glycocalyx ) Cellular communication, cell-cell recognition Receptors for hormone & bacterial toxins (cholera toxin)

24. Steroids Derived lipid Complex molecule consisting of four fused carbon ring (17C) Phenanthrene nucleus: Three 6-carbon ring (A,B, C) Cyclopentane : D ring 10, 13: methyl; 17: side chain Common cyclic ring called “steroid nucleus”/ cyclopentanoperhydrophenanthrene ring

25. Important steroids include Bile acids and salts Adrenocortical hormones Sex hormones Vitamin D Cardiac glycosides Steroids Bile salt

26. S terols If the steroid has 1/ more OH groups & no carbonyl/ carboxyl group, it is a sterol. The name terminates in – ol . Cholesterol, ergosterol , sitosterol , coprosterol Cholesterol : Major sterol in animal tissue 3: OH; 17: Aliphatic side Ergosterol : In plant & yeast, precursor of vitamin D

27. Cholesterol Cholesterol is the major sterol in animal tissues. Body cholesterol- 50% Synthesized in body (700 mg/d) 50% from Diet 70 kg man: 140 gm cholesterol Source: Egg yolk Meat Liver Brain [No vegetable oil contains any cholesterol]

28. Biomedical importance Cholesterol is widely distributed in all cells of the body but particularly in nervous tissue It is an amphipathic lipid & is an essential structural component of cell membrane. It is important for the maintenance of correct permeability & fluidity Major constituent of plasma lipoprotein Present in tissue & plasma as free/ combined with a LCFA as cholesteryl ester (storage form) Occurs in animal but not in plants or bacteria Precursor of all steroids in body including corticosteroids, sex hormones, bile acids, vitamin D

29. Plasma LDL is the vehicle that supplies cholesterol & cholesteryl ester to many tissues Free cholesterol is removed from the tissues by plasma HDL & transported to liver. It is eliminated from the body either unchanged or after conversion of bile acids (reverse cholesterol transport) Cholesterol is a major constituent of gall stone Chief factor in the genesis of atherosclerosis and heart disease Biomedical importance

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