CHAPTER IV: LIPIDS

DESCRIPTION Gk., lipos, Structurally heterogeneous group of substances of biological origin that are soluble in organic solvents, but not in water Either o Hydrophobic o Amphipathic FUNCTIONS 1. Energy Source 2. Energy reserve 3. Insulation 4. Protection 5. Cell membrane structural components 6. Chemical messengers in the human body. 7. Vitamins 8. Vitamin absorption CLASSIFICATION ACCORDING TO SOLUBILITY IN NON-POLAR SOLVENTS:

FIGURE 1: Classification of Lipids According to Solubility in Non-polar Solvents

I.

FATTY ACIDS Monocarboxylic acids that contain long, unbranched hydrocarbon chains generally 12-26 carbon atoms in length Building blocks of all saponifiable lipids o Lipids containing fatty acids: Waxes Fats and oils (triacylglycerols), Glycerophospholipids, Prostaglandins o Lipids that do not contain fatty acids: steroids Melting point depends on both the length of their hydrocarbon chains and in the degree of unsaturation (number of double bonds per molecule)
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A. SATURATED FATTY ACIDS Carbon-to-carbon chains are single bonds

NAME Butyric Caproic Caprylic Capric Lauric (Lt., Laurus) Myristic (Myristica, nutmeg genus) Palmitic (Lt., Palmitica, palm tree) Stearic (Gk., stear, hard fat) Arachidic (Lt., arachis, legume) RATIO CONDENSED FORMULA RCOOH FORMULA CH3(CH2)2COOH C3H7COOH CH3(CH2)4COOH C5H11COOH CH3(CH2)6COOH C7H15COOH CH3(CH2)8COOH C9H19COOH CH3(CH2)10COOH C11H23COOH CH3(CH2)12COOH C13H27COOH CH3(CH2)14COOH C15H31COOH CH3(CH2)16COOH C17H35COOH CH3(CH2)18COOH C19H39COOH TABLE 1: Saturated Fatty Acids SOURCES

B. UNSATURATED FATTY ACIDS Carbon chains with one or more cis double C=C bonds as shown by the kinks in the fatty acid chains. a. Monounsaturated fatty acids:
NAME Palmitoleic Acid Oleic (Latin oleum, oil) RATIO CONDENSED FORMULA RCOOH FORMULA CH3(CH2)5CH=CH(CH2)7COOH C16H31COOH CH3(CH2)7CH=CH(CH2)7COOH C16H29COOH TABLE 2: Monounsaturated Fatty Acids SOURCES

b. Polyunsaturated fatty acids Up to 6 double bonds are found in biologically important unsaturated fatty acids
NAME Linoleic Acid* Linolenic Acid* Arachidonic Acid* Eicosapentanoic Acid (EPA) Docosahexanoic Acid (DHA) RATIO CONDENSED FORMULA CH3(CH2)4CH=CH(CH2)7COOH CH3CH2CH=CHCH2CH= CHCH2CH=CH(CH2)7COOH CH3(CH2)4CH=CHCH2CH= CHCH2CH=CHCH2CH=CH (CH2)3COOH CH3CH2 (CH=CHCH2)5(CH2)2COOH RCOOH FORMULA C16H31COOH C17H29COOH C19H31COOH C19H29COOH SOURCES

TABLE 3: Polyunsaturated Fatty Acids

2 Families of Polyunsaturated Fatty Acids (Omega Classification) i. Omega-3 Fatty Acid Polyunsaturated fatty acid with its endmost double bond three carbons away from its methyl end Sources ii. Omega-6 Fatty Acids Polyunsaturated fatty acids with is endmost double bond six carbons away from its methyl end Sources:

ESSENTIAL FATTY ACIDS o Fatty acids needed by the human body and must be obtained from dietary sources because they cannot be synthesized within the body from other substances o Deficiency: o Linoleic acid, Linoeic acid, Arachidonic acid

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PROPERTY SATURATED FATTY ACID UNSATURATED FATTY ACID Chemical composition Chemical structure CC bonds within the chain Chraacterisitic group of HC Shape of HC chain Physical State (Room Temperature) Melting Point of same Chain Length Relationship between Melting Point and Chain Length TABLE 4: Similarities and Differences Between Saturated and Unsaturated Fatty Acids

II.

GLYCEROL ESTERS A. TRIACYLGLYCEROL (TAG) or TRIGLYCERIDES or NEUTRAL GLYCERIDES Compound formed by esterification of three fatty acids to glycerol o GLYCEROL o GLYCERIDES Sources: adipose tissue, butterfat, cream, olive oil, cottonseed oil, corn oil, peanut oil, lard, bacon, suet, chicken fat, fish oil Esterification: o Carboxylic acid + alcohol ester + water

Types: a. Simple fats/Glycerides b. Mixed fats/Glycerides

FIGURE 2: Mixed Glyceride

FATS AND OILS Naturally occurring mixtures of tri-esters formed from the reaction between three (3) fatty acid molecules and a glycerol molecule Formed when the hydroxyl groups of glycerol react with the carboxyl groups of fatty acids.
FATS room OILS

BASIS Physical state at temperature Source Composition Melting point

TABLE 5: Differences between Fats and Oils

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 PROPERTIES OF TRIACYLGLYCEROLS: Fats and Oils 1. Physical properties a. b. c. d. 2. Chemical properties a. GLYCERIDE FORMATION

FIGURE 5A: Formation of Glycerides

b. HYDROLYSIS Breaking down of ester linkages in the presence of catalyst (acid, base or enzyme)

H+ or enzymes + 3 H2 O 3 fatty acids +

FIGURE 6: Hydrolysis of Glycerides

c. SAPONIFICATION Hydrolysis reaction carried out in an alkaline/basic solution d. CATALYTIC HYDROGENATION Double bonds in unsaturated fatty acids react with H 2 in the presence of a Ni or Pt catalyst heated at about 200C.
Ni

CH = CH + H2

H H | | CC | | H H

FIGURE 7: Catalytic Hydrogenation of Tripalmitolean

e. RANCIDITY i. Hydrolytic rancidity ii. Oxidative rancidity Naturally occurring Synthetic

H2O, H+ Glycerol plus Fatty Acids Triglyceride NaOH Glycerol plus Fatty Acid Salts FIGURE 8: Reaction Map for Triglycerides H2, Ni A more saturated triglyceride

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B. PHOSPHOLIPIDS/PHOSPHOACYLGLYCEROLS/GLYCEROPHOSPHOLIPIDS Triester of glycerols in which two OH groups are esterified with fatty acids and the third is esterified with phosphoric acid, which in turn is esterified to an alcohol

FIGURE 9: General Structures of Phospholipids

FIGURE 10: Structures of Different Phosphoacylglyceride PHOSPHOLIPID Phosphatidic acid Phosphatidylethanolamine Phosphatidylcholine Phosphatidylserine NAME OF X Ethanolamine Choline Serine FORMULA OF X

Phosphatidylglycerol

Glycerol

TABLE 6: Prosthetic Groups for Phosphoacylglyceride

1.

Phosphatidylcholines: o Amino alcohol: o Waxy solids that form colloidal suspensions in water o Sources: egg yolks and soy beans o Synthesized by the liver o Functions Component of cell membrane Nutritive supplement: improves memory Emulsifiers: mayonnaise, ice cream and custards Aid in the transport and absorption of fatty acids
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2. Phosphatidylethanolamines and Phosphatidylserines: o Amino alcohols: o Found in heart and liver tissue and in high concentrations in the brain o Important in blood clotting 3. Plasmalogen o Ether linked alkenyl chain o Brain, heart, muscle III. NON-GLYCERIDE ESTERS A. WAXES Everyday Definition: Chemical Definition: Esters of saturated fatty acids and long-chain alcohols other than glycerol Uses: protective coatings, used in manufacturing candles.
Fatty Acid O C O Long chain alcohol

FIGURE 11: Structural Formula for Waxes

a. Beeswax from honeycomb; chiefly made up of myricyl palmitate b. Cerumen earwax; c. Spermaceti from the skull of certain whales and dolphins; chiefly made up of cetyl palmitate; used in candle making d. Chinese wax found in the secretions of insects e. Carnauba wax found in the cuticle of leaves f. Jojoba wax base of ointments

TABLE 7: Some Typical Waxes

B. SPHINGOLIPIDS Contain a long-chain amino alcohol called sphingosine, rather than glycerol SPHINGOSINE CERAMIDES

Alcohol FIGURE 10: General Structure of Sphingosine, Ceramide and Sphingolipids

a.

Sphingomyelins Sphingolipids in which the esterifying group is phosphoric acid to which choline is attached Found in all cell membranes
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Important component of myelin sheath, the protective and insulating coating that surrounds the nerves. Increases the speed of nerve impulse Contains sphingosine
NAME OF X Phosphocholine FORMULA OF X

SPHINGOLIPID Ceramide Sphingomyelin

Ganglioside GM2

Complex oligosaccharide ***GalNac: N-Acetyl D-Galactosamine ***Neu5Ac: N-acetylneuraminic acid (sialic acid)

TABLE 8: Types of Sphingomyelins

b. Glycolipids/Glycosphingolipids o Lipids containing a fatty acid, sphingosine, and carbohydrate

Figure 12: General Structure of Glycolipids

i.

ii.

iii. iv.

Glucocerebrosides/Cerebrosides Simplest of carbohydrate containing lipids Monosaccharide forms glycosidic bond with the OH of the ceramide Occur primarily in the brain (7% by dry mass) in myelin sheath of nerves Important in cellular recognition and tissue immunity Gangliosides More complex carbohydrate heads; up to seven monosaccharides bonded to ceramide Occur in gray matter of the brain as well as in the myelin sheath (i.e., brain, nerves, spleen) Present in cell membranes where they act as receptors for hormones, viruses and certain drugs Galactosyl diglycerides Sulfolipids/Galactolipids

C. STEROIDS Lipids with structures based in a fused-ring system (steroid nucleus) involving three six-membred ring and five-membered ring Steroid nucleus o Cylopentanoperhydrophenanthrene (CPPP) o consists of 3 Cyclohexane rings + 1 Cyclopentane ring o No fatty acids

FIGURE 13: Chemical Structures of the Steroid Nucleus and Cholesterol DATE DEVELOPED January 2012 Lipids DEVELOPED BY: Sunshine A. Tayaotao DOCUMENT NO. ISSUED BY: Sunshine A. Tayaotao REVISION # 00 PAGE NUMBER 7 of 14

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1. Cholesterol o Most abundant steroid in the human body which is synthesized in the liver o Derived from squalene o Found in cell membranes (up to 25% by mass), nerve tissue and brain tissue (about 10% by dry mass), and is a main component of gallstones o Considered elevated if plasma cholesterol exceeds 200 mg/dL. o Functions: starting material for the synthesis of numerous steroid hormones, vitamin D, and bile salts o Sources: nerve tissue, bile, gall stones, spleen, kidney, brain, sweet breads, liver, egg yolk; whole milk, butter, fish roe, cheese, ice cream, meats 2. Bile Salts o Emulsifying agents that make dietary lipids soluble in the aqueous environment in the digestive tract o Product of cholesterol oxidation o Source is bile 3. Steroid Hormones o ANABOLIC STEROIDS Derivatives of testosterone Serious ADRs Increase blood lipid levels very high risk for heart diseases Liver toxicity Male reproduction system alteration Female:

FIGURE 14: Chemical Structures of Some Anabolic Steroids

HORMONES Produced from cholesterol Chemical messengers produced by ductless glands

o Classes of Steroids: a. Sex hormones Controls reproduction and secondary sex characteristics i. Estrogens Female sex hormones, synthesized in the ovaries and adrenal cortex Example: Functions: Responsible for the development of female secondary characteristics at the onset of puberty Regulation of menstrual cycle Stimulate development of mammary glands during pregnancy Induce estrus in animals Androgens Male sex hormones; synthesized in testes and adrenal cortex Example: Functions: Responsible for the development of male secondary characteristics Promote muscle growth
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ii.

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FIGURE 15: Chemical Structures of Sex Hormones with their Biological Effects

iii.

Progestins Pregnancy hormones; synthesized in ovaries and placenta Example: Functions Prepare lining of the uterus for the implantation of fertilized ovum Suppresses ovulation

b. Adrenocortical hormones Regulate numerous biochemical processes in the body Produced by adrenal glands located on the top of each kidney. i. Mineralocorticoids Control the balance of Na+ and K+ ions in the body ALDOSTERONE

FIGURE 16: Chemical Structures of Adrenocortical Hormones with their Biological Effects

ii.

Glucocorticoids Control glucose metabolism and counteract inflammation CORTISOL Cortisone

4. Eicosanoids o Oxygenated derivatives of polyunsaturated 20-carbon fatty acids o Precursor: o Gk., eikos o Exert effects in the tissues where they are synthesized
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Physiological effects: The inflammatory response, a normal response to tissue damage The production of pain and fever The regulation of blood pressure The induction of blood clotting The control of reproduction functions, such as induction of labor The regulation of sleep/wake cycle

a. Prostaglandins (PG) 20-carbon fatty acid derivatives that contain a cyclopentane ring and oxygen-containing functional groups PGE soluble in ether; with ketone group at C-9 PGF soluble in phosphate buffer, fosfat (Swedish); hydroxyl group b. Thromboxanes (TX) 20-carbon fatty acid derivatives that contain a cyclic ether and oxygen-containing functional groups Produced by blood platelets c. Leukotrienes (LT) 20-carbon fatty acid derivatives that contain three conjugated double bonds and hydroxyl groups Found in leukocytes (white blood cells)

FIGURE 17: Formation of Eicosanoids

5. Fat Soluble Vitamins (Vitamin chapter) IV. COMPLEX LIPIDS 1. Aminolipids/Lipoproteins Combined lipids with proteins and phospholipids. Soluble in water because the surface consists of polar lipids. Differ in density, composition, and function. Parts: o Hydrophobic core o Hydrophilic surface Types: a. CHYLOMICRONS b. VLDL (Very Low Density Lipoprotein) c. IDL ( Intermediate Density Lipoprotein) d. LDL (Low Density Lipoprotein) e. HDL (High Density Lipoprotein)

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FIGURE 20: Formation of Arterial Plaques

CLASSIFICATION OF LIPIDS ON THE BASIS OF COMPOSITION/STRUCTURE

FIGURE 21: Classification of Lipids According to Composition or Structure

1.

Simple lipids: a. Triglycerides/Triacylglycerol (TAG) i. Fats: ii. Oils are b. Ester of fatty acids and high MW alcohols other than glycerol i. Waxes ii. Cholesteryl esters iii. Vitamin D and A esters

2. Complex lipids: a. Phospholipids i. Glycerophospholipids/Phosphoglycerides alcohol Lecithins Cephalins Plasmalogen ii. Sphingophospholipids/Phosphosphingosides alcohol: Sphingomyelins
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b. Glycolipids/Glycosphingolipids i. Glucocerebrosides ii. Gangliosides iii. Galactosyl diglycerides iv. Sulfolipids/Galactolipids c. Other complex lipids i. Aminolipids/Lipoproteins

3. Precursor and derived lipids: a. Fatty acids i. Saturated fatty acids ii. Unsaturated fatty acids 1. Monounsaturated 2. Polyunsaturated iii. Cyclic fatty acids b. Alcohols i. Glycerol ii. Sterol iii. Cholesterol iv. Ergosterol v. Calciferol c. Sphingosine

CLASSIFICATION ON THE BASIS OF SAPONIFICATION:

FIGURE 22: Classification of Lipids According to Saponification

CELL MEMBRANES Separate cellular contents from the external environment. Consist of a lipid bilayer made of two rows of phospholipids.

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 FLUID MOSAIC MODEL OF CELL MEMBRANES Contains proteins, carbohydrates, and cholesterol. Other substances o Cholesterol o Glycolipids on surface o Proteins embedded in bilayer o Proteins on surface o Unsaturated fatty acids o Have proteins and carbohydrates on the surface

FIGURE 23: Diagram of a Cell Membrane

The transport of substances through cell membranes involves o Diffusion o Facilitated transport o Active transport

FIGURE 24: Types of Cell Membrane Transport

DISORDERS OF LIPID METABOLISM (Lipidoses) 1. Gaucher's Disease Caused by a buildup of glucocerebrosides, a product of fat metabolism, in tissues. Most common among Ashkenazi (Eastern European) Jews Leads to an enlarged liver and spleen and a brownish pigmentation of the skin. Accumulation o Eyes o Bone marrow
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2. Tay-Sachs Disease Caused by a buildup of gangliosides (GM2), products of fat metabolism, in the brain and spleen owing to lack of the enzyme hexosaminidase A. Most common among families of Eastern European Jewish origin. 3. Fabry's Disease Caused by a buildup of glycolipid, a product of fat metabolism, in tissues. Causes skin growths, pain in the extremities, poor vision, recurrent episodes of fever, and kidney or heart failure. 4. Niemann-Pick Disease Caused by a buildup of sphingomyelin or cholesterol in the brain, spleen and liver due to a deficiency of sphingomyelinase The most severe forms tend to occur in Jewish people. The milder forms occur in all ethnic groups. o Type A o Type B o Type C
DISEASE LIPID STORED TYPE ENZYME ABSENT Fabrys Gal-gal-glucosylceramide Ganglioside galactosidase Gauchers Glucosylceramide Cerebroside glucosidase Niemann-Pick Sphingomyelin Sphingolipid Sphingomyelinase Tay-Sachs GM2 Ganglioside Ganglioside Hexosaminidase A TABLE 9: Summary of the Different Lipid Metabolism Disorders

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