Paper : 05 Metabolism of Lipids Module: 01 Prologue to Lipids Principal Investigator Dr. Sunil Kumar Khare, Professor, Department of Chemistry, IIT-Delhi Paper Coordinator and Dr. Suaib Luqman, Scientist (CSIR-CIMAP) Content Writer & Assistant Professor (AcSIR) CSIRDr. Vijaya-CIMAP, Khader Lucknow Dr. MC Varadaraj Content Reviewer Prof. Prashant Mishra, Professor, Department of Biochemical Engineering and Biotechnology, IIT-Delhi 1 METABOLISM OF LIPIDS Biochemistry Prologue to Lipids DESCRIPTION OF MODULE Subject Name Biochemistry Paper Name 05 Metabolism of Lipids Module Name/Title 01 Prologue to Lipids 2 METABOLISM OF LIPIDS Biochemistry Prologue to Lipids 1. Objectives To understand what is lipid Why they are important How they occur in nature 2. Concept Map LIPIDS Fatty Acids Glycerol 3. Description 3.1 Prologue to Lipids In 1943, the term lipid was first used by BLOOR, a German biochemist. Lipids are heterogeneous group of compounds present in plants and animal tissues related either actually or potentially to the fatty acids. They are amphipathic molecules, hydrophobic in nature originated utterly or in part by thioesters (carbanion-based condensations of fatty acids and/or polyketides etc) or by isoprene units (carbocation-based condensations of prenols, sterols, etc). Lipids have the universal property of being: i. Quite insoluble in water (polar solvent) ii. Soluble in benzene, chloroform, ether (non-polar solvent) 3 METABOLISM OF LIPIDS Biochemistry Prologue to Lipids Thus, lipids include oils, fats, waxes, steroids, vitamins (A, D, E and K) and related compounds, such as phospholipids, triglycerides, diglycerides, monoglycerides and others, which are allied more by their physical properties than by their chemical assests. They are vital constituents related to diet because of high energy value, essential fatty acids and fat soluble vitamins present in the content of fat foods. Lipids serve as adept source of energy when stored in adipose tissue. Fat also dole out as Thermal Insulators in the subcutaneous tissues and in the region of some organs and non- polar lipids acts as Electrical Insulators permitting quick propagation of depolarization waves by the side of myelinated nerves. Lipoproteins (combinations of lipid and protein) transport lipids in the blood and the biochemical acquaintance of lipids is obligatory in understanding atherosclerosis, diabetes mellitus, obesity etc. The function of diverse polyunsaturated fatty acids (PUFAs) in nutrition and health can also be best understood by studying its biochemical profile. Chemically, lipids are defined as esters of glycerol and fatty acids or else refer as the triglycerides of fatty acids. They are the substances of natural origin, soluble in non-polar solvents and hence may be extorted by using organic solvents such as methanol. Lipids could be fractionated by either using adsorption chromatography (thin layer chromatography) or reverse-phase chromatography. Fatty acid It may be defined as an organic acid that occurs in a natural triglyceride and is a mono carboxylic acid ranging in chain length from C4-C24 carbon atoms. Fatty acids are obtained from the hydrolysis of fats. They are naturally occurring straight chain derivatives containing carbon atoms with even numbers (4-28) as they assemble from two carbon units. Typically derived from triglycerides or phospholipids, fatty acids are vital sources of fuel yielding huge quantities of ATP. Fatty acids that contain C=C are recognized as unsaturated fatty 4 METABOLISM OF LIPIDS Biochemistry Prologue to Lipids acid (UFAs) and those lacking double bonds are recognized as saturated fatty acid (SFAs). They are named after corresponding hydrocarbons and vary in length. UFAs end with suffix-enoic and SFAs ends with suffix-anoic. Based on length as short to very long, they may be categorized as under: SCFA: Short Chain Fatty Acids with less than six carbons (e.g. butyric acid). MCFA: Medium Chain Fatty Acids with 6-12 carbons. LCFA: Long Chain Fatty Acids with 13-21 carbons. VLCFA: Very Long Chain Fatty Acids with more than 22 carbons. The condensation of Acetyl Co-A, a coenzyme, results in the biosynthesis of fatty acids as it carries two carbon units. That is why all FAs have even numbers of carbon atoms. 5 METABOLISM OF LIPIDS Biochemistry Prologue to Lipids Unsaturated Fatty Acid (UFA) UFAs contain carbon units linked by double bonds, saturated with hydrogen atoms that convert double bonds to single bonds (one or more double bonds between carbon units). The carbon atoms occur either in a cis or a trans configuration. When two hydrogen atoms nearby to the double bond fasten on the chain (same side), it is cis configuration of fatty acid (Oleic acid, Linoleic acid etc). When the neighboring two hydrogen atoms lie on the chain (opposite side), it is trans configuration of fatty acid (Elaidic acid, Vaccenic acid etc). Unsaturated fatty acid may be of following types. Monounsaturated: Presence of one double bond Polyunsaturated: Presence of two or more double bond Eicosanoid: are signaling molecules made by the oxidation of 20-carbon fatty acids Prostanoid: It includes (a) Prostaglandins e.g. PGE1, (b) Prostacyclin e.g. PCI2, (c) Thromboxanes e.g. TXA2 Leukotriene: Containing three double bonds sequentially e.g. LTB4, LTE4 Table 1. Selected examples of Unsaturated Fatty Acids n-x Name Structure & Chemical Formula C:D Δx n-3 18:3 cis,cis,cis- α-Linolenic acid CH CH CH=CHCH CH=CHCH CH=CH(CH ) COOH 3 2 2 2 2 7 Δ9,Δ12,Δ15 20:5 cis,cis,cis,ci Eicosapentaenoic CH CH CH=CHCH CH=CHCH CH=CHCH CH=CHCH CH=CH(CH ) 3 2 2 2 2 2 2 3 s,cis-Δ5, Δ8, acid COOH Δ11, Δ14, Δ17 22:6 cis,cis,cis,ci 4 Docosahexaenoi CH3CH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CHCH2C s,cis,cis-Δ , 7 10 13 c acid H=CH(CH2)2COOH Δ , Δ , Δ , Δ16, Δ19 9 n-5 Myristoleic acid CH3(CH2)3CH=CH(CH2)7COOH 14:1 cis-Δ n-6 18:2 cis,cis-Δ9, Linoleic acid CH (CH ) CH=CHCH CH=CH(CH ) COOH 3 2 4 2 2 7 Δ12 18:2 trans,trans- Linoelaidic acid CH (CH ) CH=CHCH CH=CH(CH ) COOH 3 2 4 2 2 7 Δ9, Δ12 6 METABOLISM OF LIPIDS Biochemistry Prologue to Lipids 20:4 cis,cis,cis,ci 5 8 11 Arachidonic acid CH3(CH2)4CH=CHCH2CH=CHCH2CH=CHCH2CH=CH(CH2)3COOH s-Δ Δ , Δ , Δ14 9 n-7 Palmitoleic acid CH3(CH2)5CH=CH(CH2)7COOH 16:1 cis-Δ 11 Vaccenic acid CH3(CH2)5CH=CH(CH2)9COOH 18:1 trans-Δ 9 n-9 Oleic acid CH3(CH2)7CH=CH(CH2)7COOH 18:1 cis-Δ 9 Elaidic acid CH3(CH2)7CH=CH(CH2)7COOH 18:1 trans-Δ 13 Erucic acid CH3(CH2)7CH=CH(CH2)11COOH 22:1 cis-Δ 6 n-10 Sapienic acid CH3(CH2)8CH=CH(CH2)4COOH 16:1 cis-Δ C:D = Number of carbon units and double bond ratio Adapted and Modified from http://en.wikipedia.org/wiki/Fatty_acid Table 2. List of Other Unstaurated Fatty Acids C:D ω-n Name Structure & Chemical Formula Δn Configuration Source 16:1 Palmitoleic CH (CH ) CH=CH(CH ) COOH Δ9 cis Macadamia nut ω-7 3 2 5 2 7 acid 18:1 Vaccenic CH (CH ) CH=CH(CH ) COOH Δ11 Butter, Milk, ω-7 3 2 5 2 9 trans acid and Yogurt Δ9 Canola, Olive ω-9 Oleic acid CH (CH ) CH=CH(CH ) COOH cis 3 2 7 2 7 and Pecan oil Δ9 Vegetable oil ω-9 Elaidic acid CH (CH ) CH=CH(CH ) COOH trans 3 2 7 2 7 (hydrogenated) 18:2 Δ9,12 Chicken fat, ω-6 Linoleic acid CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH cis Olive and Peanut oil 18:3 Δ9,12,1 Chiaseeds, α-Linolenic CH CH CH=CHCH CH=CHCH CH=CH(CH ω-3 3 2 2 2 5 cis Flaxseeds and acid ) COOH 2 7 Walnuts Δ6,9,12 Black currant oil, Borage oil, γ-Linolenic CH (CH ) CH=CHCH CH=CHCH CH=CH( ω-6 3 2 4 2 2 cis Evening acid CH ) COOH 2 4 primrose oil and safflower oil 18:4 Δ6,9,12, Blackcurrant, Stearidonic CH CH CH=CHCH CH=CHCH CH=CHCH 15 Corn gromwell ω-3 3 2 2 2 2 cis acid CH=CH(CH2)4COOH and Seed oils of hemp 20:1 Paullinic Δ13 ω-7 CH (CH ) CH=CH(CH ) COOH cis Guarana acid 3 2 5 2 11 Δ11 Jojoba oil (non- Gondoic ω-9 CH (CH ) CH=CH(CH ) COOH cis caloric and non- acid 3 2 7 2 9 digestible but 7 METABOLISM OF LIPIDS Biochemistry Prologue to Lipids edible) 20:3 Dihomo-γ- Δ8,11,1 Trace amounts CH (CH ) CH=CHCH CH=CHCH CH=CH( ω-6 linolenic 3 2 4 2 2 4 cis (Animal CH ) COOH acid 2 6 products) CH (CH ) CH=CHCH CH=CHCH CH=CH( Δ5,8,11 ω-9 Mead acid 3 2 7 2 2 cis Cartilage CH2)3COOH 5,8,11, 20:4 Arachidonic CH3(CH2)4CH=CHCH2CH=CHCH2CH=CHC Δ Dairy, Eggs, ω-6 14 cis acid H2CH=CH(CH2)3COOH Meat 20:5 Δ5,8,11, Cod liver, 14,17 Herring, Eicosapenta CH CH CH=CHCH CH=CHCH CH=CHCH Menhaden, ω-3 3 2 2 2 2 cis enoic acid CH=CHCH2CH=CH(CH2)3COOH Mackerel, Salmon and Sardine 22:1 Δ13 Mustard oil, ω-9 Erucic acid CH (CH ) CH=CH(CH ) COOH cis 3 2 7 2 11 Wallflower seed 7,10,1 22:4 Docosatetrae CH3(CH2)4CH=CHCH2CH=CHCH2CH=CHC Δ ω-6 3,16 cis - noic acid H2CH=CH(CH2)5COOH 22:6 CH CH CH=CHCH CH=CHCH CH=CHCH Δ4,7,10, Docosahexa 3 2 2 2 2 Fish oil and ω-3 CH=CHCH CH=CHCH CH=CH(CH ) COO 13,16,19 cis enoic acid 2 2 2 2 Maternal milk H 24:1 Δ15 Flaxseed, King Salmon, Nervonic Macademia ω-9 CH (CH ) CH=CH(CH ) COOH cis acid 3 2 7 2 13 nuts, Sesame seed and Sockeye salmon Saturated Fatty Acid (SFA) They are long chain carboxylic acids without double bonds but with 12-24 carbon units.