LIPIDS

Definition: Made up of C, H and O Lipids are hydrophobic compounds. insoluble or poorly soluble in water, Readily soluble in non-polar solvents such as ( ether, benzene, acetone, chloroform)

Biological Functions of Lipids As an energy source, lipids provide 9 kcal of energy per gram Triglycerides provide energy storage in adipocytes Phosphoglycerides, sphingolipids, and steroids are structural components of cell membranes Steroid hormones are critical intercellular messengers Lipid-soluble vitamins (A, E, D, K) Dietary fat acts as a carrier of lipid-soluble vitamins into cells of small intestine Provide shock absorption and insulation

Biomedical importance of lipids: They are a major source of energy; the yield from the oxidation of fatty acids is 9 kcal/g fat compared to 4 kcal/g protein or carbohydrate. 2. Fat stored in adipose tissue serves as thermal insulator in the subcutaneous tissue and protective around certain organs (e.g. kidney). 3. Lipids act as electrical insulators in myelinated nerves to allow rapid propagation of nerve impulses.

4. Cholesterol is an important constituent of the cell membrane and is essential for the synthesis of steroid hormones, bile acids and vitamin D. 5. Fat-soluble vitamins, steroid hormones and eicosanoids play important regulatory roles in the body.

7. Lipoproteins (e.g. LDL & HDL) are a mean for transporting lipids in blood. 8. Imbalance in lipid metabolism can lead to major clinical problems such as obesity and atherosclerosis

Fatty Acids Fatty acids are water-insoluble. Long straight-chain carboxylic acids no branching Most common chains range from 10–20 carbons in length Can be saturated (containing no double bonds) or unsaturated (containing one or more double bonds that are always separated at 3 carbon intervals), but usually no other functional groups present The general formula of saturated fatty acids is: CH3 - ( CH2)n – COOH Any fatty acid that cannot be synthesized by the body is called an essential fatty acid

Fatty Acid Nomenclature Nomenclature reflects location of double bonds also used are common names (e.g., oleic, stearic, palmitic)

Carbon atoms in a fatty acid are numbered by 2 different systems: Beginning from the carboxyl carbon (Δ delta end) as carbon 1, where numeric designation of the fatty acid shows the number of carbon atoms 2- followed by the number of double bonds, 3- then the site of unsaturation. 4 2 16 1 3 15 COOH

Palmitic acid: CH3(CH2)14COOH ; 16:0 (16:0 indicates a fatty acid with 16 carbons and no double bonds). Oleic acid: CH3(CH2)7C=C(CH2)7COOH ; 18:1 Δ 9 (18:1 Δ 9 indicates a fatty acid with 18 carbons and one double bond between carbons 9 and 10).

Linoleic acid: CH3 (CH2) 4C=CCH2C=C(CH2) 7COOH ; 18:2 Δ 9,12 (18:2 Δ 9,12 indicates a fatty acid with 18 carbons and 2 double bonds between carbons 9 and 10 and carbons 12 and13). Linolenic acid: CH3CH2C=CCH2C=CCH2C=C(CH2) 7COOH; 18:3 Δ 9,12,15 (18:3 Δ 9,12,15 indicates a fatty acid with 18 carbons and 3 double bonds between carbons 9 and 10, carbons 12 and 13 and carbons 15 and 16).

Arachidonic acid: CH3 (CH2) 3(CH2C=C) 4(CH2) 3COOH; 20:4 Δ 5,8,11,14 (20:4 Δ 5,8,11,14 indicates a fatty acid with 20 carbons and 4 double bonds between carbons 5 and 6, carbons 8 and 9, carbons 11 and 12 and carbons 14 and 15).

2. Beginning with the terminal methyl carbon (known as omega ώ carbon) as carbon 1, where ώ-3 for example indicates that; The closest double bond to the terminal methyl group begins after 3 carbons from that end. Therefore, linoleic acid ; is an ώ -6 fatty acid CH3 (CH2) 4C=CCH2C=C(CH2) 7COOH ώ -6,18:2 Δ 9,12 linolenic acid ;is an ώ -3 fatty acid. CH3CH2C=CCH2C=CCH2C=C(CH2) 7COOH ώ -3,18:3Δ9,12,15

Fatty Acid Properties Melting point increases with increasing carbon number Melting point of a saturated fatty acid is higher than an unsaturated fatty acid with the same number of carbons Typical saturated fatty acids are tightly packed together cis double bonds prevent good alignment of molecules in unsaturated fatty acids leading to poor packing Double bonds lower melting point relative to saturated acid

Common Fatty Acids

Saturated & Unsaturated Fatty Acids A. Saturated Fatty Acids: No of Double Bonds No of Carbon Atoms Name 12 Lauric (12:0) 14 Myristic (14:0) 16 Palmitic (16:0) 18 Stearic (18:0) Saturated fatty acids do not have double bonds. They are formed inside the body.

Saturated Fatty Acids Octanoic Acid

B. Unsaturated Fatty Acids: No of Double Bonds No of Carbon Atoms Name 1 16 Palmitoleic (16:1) 18 Oleic (18:1) 2 Linoleic (18:2) 3 Linolenic (18:3) 4 20 Arachidonic (20:4) The first double bond is usually at the ninth carbon The double bond is normally in a cis configuration Double bonds lower the melting temperature The cis configuration doesn’t allow fatty acids to pack as close together

Saturated vs. Unsaturated Fatty Acids saturated: the SFA’s of a lipid have no double bonds between carbons in chain polyunsaturated: more than one double bond in the chain most common polyunsaturated fats contain the polyunsaturated fatty acids (PUFAs) oleic, linoleic and linolenic acid unsaturated fats have lower melting points stearic (SFA) melts at 70oC, oleic (PUFA) at 26oC

Unsaturated fatty acids have one or more double bonds Unsaturated fatty acids have one or more double bonds. There are 2 types: Essential fatty acids: These fatty acids are with more than one double bond, e.g. linoleic, linolenic and arachidonic, they are not formed in the body and should be obtained from the diet. Non-essential fatty acids: These can be synthesized in the body.

Unsaturated Fatty Acids 3 - Octenoic Acid 3, 6 - Octadienoic Acid Short hand: 8:1 (D3) 8:2 (D3,6)

Polyunsaturated Fatty Acids Linoleic acid: Cis, cis, 9, 12 - Octadecadienoic acid Linolenic acid: Cis, cis, cis 9, 12, 15 - Octadecatrienoic acid Arachidonic acid: Cis, cis, cis, cis 5, 8, 11, 14 - Eicosatetraenoic acid   Linoleic Acid Linolenic Acid Arachidonic Acid

Saturated vs. Unsaturated Fats saturated fats tightly packed, clog arteries as atherosclerosis because of double bonds, polyunsaturated fats do not pack well -- like building a wall with bricks vs. irregular-shaped objects plant fats are much higher in PUFA’s than animal fats

Cis And Trans Fatty Acids Cis 9 - Octadecenoic Acid (oleic) Trans 9 - Octadecenoic Acid (elaidic acid)

Naturally-occurring fatty acids 1. Cis form 2. Not conjugated --- isolated double bond. 3. Even numbered fatty acids.

CLASSIFICATION OF FATTY ACIDS PRESENT AS GLYCERIDES IN FOOD FATS Common Name Systematic Name Formula Common source   I. Saturated Fatty Acids   Butyric Butanoic CH3(CH2)2COOH butterfat butterfat, coconut and palm nut oils Caproic Hexanoic CH3(CH2)4COOH Caprylic Octanoic CH3(CH2)6COOH coconut and palm nut oils, butterfat Capric Decanoic CH3(CH2)8COOH coconut and palm nut oils, butterfat Lauric Dodecanoic CH3(CH2)10COOH coconut and palm nut oils, butterfat Myristic Tetradecanoic CH3(CH2)12COOH coconut and Palm nut oil, most animal and plant fats Palmitic Hexadecanoic CH3(CH2)14COOH practically all animal and plant fats Stearic Octadecanoic CH3(CH2)16COOH animal fats and minor component of plant fats Arachidic Eicosanoic CH3(CH2)18COOH peanut oil

II. Unsaturated Fatty Acids Common Name Systematic Name Formula Common source   II. Unsaturated Fatty Acids   A. Monoethenoic Acids   Oleic Cis 9-octadecenoic C17H33COOH plant and animal fats Elaidic Trans 9-Octadecenoic C17H33COOH animal fats B. Diethenoic Acids peanut, linseed, and cottonseed oils Linoleic 9,12-Octadecadienoic C17H31COOH C. Triethenoid Acids   9,12,15-Octadecatrienoic C17H29COOH linseed and other seed oils Linolenic Eleostearic 9,11,13-Octadecatrienoic C17H29COOH peanut seed fats D. Tetraethenoid Acids fish oils Moroctic 4,8,12,15-Octadecatetraenoic C17H27COOH Arachidonic 5,8,11,14-Eicosatetraenoic C19H31COOH traces in animal fats

Common and Systematic Names of Fatty Acids   Common Name Systematic Name Formula Common source   A. Monoethenoic Acids   Cis 9-octadecenoic C17H33COOH plant and animal fats Oleic Trans 9-Octadecenoic C17H33COOH animal fats Elaidic B. Diethenoic Acids 9,12-Octadecadienoic C17H31COOH peanut, linseed, and cottonseed oils Linoleic C. Triethenoid Acids   Linolenic 9,12,15-Octadecatrienoic C17H29COOH linseed and other seed oils 9,11,13-Octadecatrienoic C17H29COOH peanut seed fats Eleostearic D. Tetraethenoid Acids Moroctic 4,8,12,15-Octadecatetraenoic C17H27COOH fish oils Arachidonic 5,8,11,14-Eicosatetraenoic C19H31COOH traces in animal fats

Biomedical importance of fatty acids: Human body can synthesize various fatty acids with the exception of; “linoleic” and “linolenic” acids; this is because body tissues cannot introduce double bonds beyond the Δ 9 position. In contrast, plants are able to introduce double bonds at the Δ 12 and Δ 15 positions. Therefore, linoleic acid and linolenic acid are considered as nutritionally essential fatty acids, and must be supplied in a diet of plant origin or from animals that have consumed these plant fats.

1. Dietary ώ -3 fatty acids (in fish oil and plant fats) can reduce serum triglycerides, thrombosis and the risk of cardiovascular mortality. 2- ώ -6 fatty acids (in olive oil and corn oil) lower plasma cholesterol and protect against coronary heart disease. 3-Generally, a high ratio of polyunsaturated fatty acids to saturated fatty acids in the diet is a major factor to prevent coronary heart disease.

Eicosanoids: Prostaglandins, Leukotrienes, and Thromboxanes Fatty acids which can’t be synthesized by the body are essential fatty acids Linoleic acid is an essential fatty acid required to make arachadonic acid Arachidonic acid (20 C) is the eicosanoid precursor Eicosanoids are three groups of structurally related compounds Prostaglandins Leukotrienes Thromboxanes

Prostaglandins Potent biological molecules They act like hormones in controlling the body’s processes Structure Synthesized from 20-carbon unsaturated fatty acids Cyclic compounds including a 5-carbon ring Names are based on ring substituents and number of side-chain double bonds Made in most tissues Exert their effects on cells that produce them and cells in the immediate vicinity

Biological Processes Regulated by Eicosanoids Blood clotting Thromboxane A2 stimulates constriction of blood vessels and platelet aggregation Prostacyclin dilates blood vessels and inhibits platelet aggregation Inflammatory response Prostaglandins mediate aspects of inflammatory response Reproductive system Stimulation of smooth muscle by PGE2

Biological Processes Regulated by Eicosanoids Gastrointestinal tract Prostaglandins inhibit gastric secretion Inhibition of hormone-sensitive lipases Prostaglandins increase secretion of protective mucus Kidneys Prostaglandins dilate renal blood vessels Results in increased water and electrolyte excretion Respiratory tract Leukotrienes promote the constriction of bronchi Prostaglandins promote bronchodilation

Structures of Four Prostaglandins

Aspirin and Prostaglandins Aspirin inhibits prostaglandin synthesis by acetylating cyclooxygenase, an enzyme necessary for prostaglandin synthesis

Overview of Prostaglandin Synthesis From Arachidonic Acid