Medical biochemistry & Molecular Biology Department Lipids Chemistry Dr. Magda Ibrahim Medical biochemistry & Molecular Biology Department Dr. Magda Ibrahim Lecturer of medical biochemistry and molecular biology

State the definition and classification of lipids. Recognize the general structure and characters of fatty acids. List the four main classes of unsaturated fatty acids Define essential fatty acids Explain the physiological importance of omega 3 fatty acids Classify phospholipids and state their functions in the body Describe structure and significance of glycolipids Describe the steroid nucleus, cholesterol molecule and its derivatives By the end of this topic, you should be able to :

Classification of lipids Introduction Definition of lipids Functions of lipids (energy, Fat soluble vitamins, cell membrane, thermal insulator, electrical insulator) Classification of lipids Simple lipid 1- Oil/fat 2- wax Complex lipids (glycolipid, phosphlipids,sulfolipids, lipoprotein) Derived lipids (fatty acids, glycerol, keton bodies) Polyprenoid compound (steroids, terpenes) Characteristics Fatty acids (amphipathic, straight chain, even number, saturated/un saturated) Double bond Poly unsaturated fatty acids (essential fatty acids) + their function

Lipids Heterogeneous group of compounds which are soluble in organic solvents ( ether, chloroform) and insoluble in water. For example: fat, oils, steroids, wax They are related either actually or potentially to fatty acids

They are not polymers (not formed of repeating units. What are polymers? Give an examples Polymers as polysaccharides, proteins, DNA, RNA.

What are the functions of lipids? Important dietary constituents, because of their high energy value. Fat-soluble vitamins (DEKA) it serves as a thermal insulator in the subcutaneous tissues and around certain organs. Electrical insulators around myelinated nerves Cell membrane structure.

Classification of lipids Substances associated with lipids ( polyprenoid compounds) Simple lipids Compound lipids Derived lipids

1- Simple lipids (They are ester of fatty acid and alcohol) Oils or fat (TAG) They are ester of fatty acid + glycerol Oil--- liquid at room temp Fat---solid at room temp TAG;triacylglycerol Wax They are ester of fatty acid + high molecular monohydric alcohol (alcohol has 16-30 carbon) Bee wax, lanoline

II- Compound lipids (ester or amides of fatty acid+ alcohol+ additional group) Lipoproteins Contain proteins Phospholipids (contain phosphate) Sulfolipids Contain sulfate Glycolipids contain carbohydrate

III- Derived lipids Theses are produced from the hydrolysis or digestion of simple or compound lipids. For example: Fatty acids, glycerol, sphingosine.

VI- Polyprenoid compounds A group of compounds which contains isoprene units They are two classes: 1- Steroids: are derivatives of the hydrocarbon ring system of cholesterol as cholesterol. Also, fat soluble vitamins (EKA) are synthesized from isoprene units. 2- Terpenes in plants

Classification of lipids Introduction Definition of lipids Functions of lipids (energy, Fat soluble vitamins, cell membrane, thermal insulator, electrical insulator) Classification of lipids Simple lipid 1- Oil/fat 2- wax Complex lipids (glycolipid, phosphlipids,sulfolipids, lipoprotein) Derived lipids (fatty acids, glycerol) Polyprenoid compounds (steroids, terpenes) Characteristics Fatty acids (amphipathic, straight chain, even number, saturated/un saturated) Double bond Poly unsaturated fatty acids (essential fatty acids) + their function

Fatty acids They are aliphatic carboxylic acid. They are represented as R-COOH, where R is hydrocarbon chain. Fatty acids are named after the hydrocarbon of the same number of carbon. The suffix (oic) being substituted for the final (e) For example: 1C methane (Methanoic) HCOOH 2C Ethane (Ethanoic) CH3-COOH

General properties of fatty acid in natural lipid They are mono carboxylic (only one –COOH-), which is completely ionized in plasma. - So, fatty acids are amphipathic as it contain Hydrophilic part (carboxyl group) Hydrophobic part (hydrocarbon chain)

(2) They have long straight chains: Short chain----- up to 5 carbon Medium chain-----6-10 carbon Except, phytanic acid is branched (3)Most naturally fatty acids have even number of carbon atoms (they are synthesized from 2-carbon unit).Plants and marine organsim have odd number fatty acids. Some fatty acids contain a hydroxyl group (cerebronic acid)

Saturated fatty acids

Unsaturated fatty either mono or poly- unsaturated (4)May be saturated or unsaturated (the presence of double bound called unsaturated) Unsaturated fatty either mono or poly- unsaturated The double bound are always separated from each other by methylene group (-CH2-) They are neither adjacent nor conjugated (conjugated i.e alternating with single bonds) Saturated fatty acid Un-saturated fatty acid

The presence of double bound produces Cis-trans isomerism - The two bulky groups are at the same side of the bond (cis). - The hydrocarbon chain bent 120 at the double bond giving an L- shape -Nearly all fatty acid in cis form The two bulky groups are at the opposite side of the bond (Trans)

Compare between cis and trans isomers Cis- isomers The two bulky groups are at the same side of the bond Less thermal stable, the have lower melting temp Melting temp: the temperature at which a substance changes from solid to liquid state. Trans- isomers The two bulky groups are at the opposite side of the bond More thermal stable, need high melting temp. They are products the process of hydrogenation of oil The are nearer to corresponding saturated fatty acid. They are metabolized like saturated fatty acids. So, they tend to increase cholesterol in blood.

French fries, doughunts, and cookies are rich in trans fatty acids. Try to avoid these food in diet. Trans fatty acids tend to increase cholesterol level.

The melting point of fatty acid decreases if the fatty acids are shorter and have more double bonds Short fatty acids (up to 5C) and medium chain fatty acids (6-10C) are liquid at room temp. Longer chain fatty acids (more than 10C) are solid at room temp. Unsaturated fatty acids have low melting temp and are liquid at room temp.

General properties of fatty acid in natural lipids Amphipathic Straight chain Even number May be saturated or not

The presence of double bond in fatty acid is characterized by: 1- separated by methylene (CH2) bridges 2- Not adjacent 3- not conjugated 4- Cis-trans isomers

Classification of lipids Introduction Definition of lipids Functions of lipids (energy, Fat soluble vitamins, cell membrane, thermal insulator, electrical insulator) Classification of lipids Simple lipid 1- Oil/fat 2- wax Complex lipids (glycolipid, phosphlipids,sulfolipids, lipoprotein) Derived lipids (fatty acids, glycerol, keton bodies) Polyprenoid compound (steroids, terpenes) Characteristics Fatty acids (amphipathic, straight chain, even number, saturated/un saturated) Double bond (separated by methylene group, not adjacent/not conjugated, cis/trans isomers) Poly unsaturated fatty acids (essential fatty acids) + their function

Numbering of fatty acids CH3-CH2-CH2-CH2-CH2-COOH Δ numbering 6 5 4 3 2 1 Greek lettering ε δ γ β α ω (omega) ω-1 ω-2 ω-3 ω-4 ω-5 Palmitic: 16:0 Oleic acid: 18:1 Δ9 1= double bond Δ 9= double bond between 9-10

1- The double bond can be related to the carboxyl (C1) Oleic C:18:1(9) or C18: 19 The double bond is between 9 and 10 26

2- The double bond can be related to the ω (omega) carbon of the fatty acid - Unsaturated FA are classified into ώ 3,6,7 and 9 Family CH3-(CH2)7-CH=CH-(CH2)7-COOH Oleic 18: 19 or 18:19 class:9 family CH3-(CH2) 4CH=CH-CH2-CH=CH-(CH2) 7-COOH Linoleic 18: 29 ,12 or18:26,9 class:6family 27

Parent fatty acids

Classification of lipids Introduction Definition of lipids Functions of lipids (energy, Fat soluble vitamins, cell membrane, thermal insulator, electrical insulator) Classification of lipids Simple lipid 1- Oil/fat 2- wax Complex lipids (glycolipid, phosphlipids,sulfolipids, lipoprotein) Derived lipids (fatty acids, glycerol, keton bodies) Polyprenoid compounds (steroids, terpenes) Characteristics Fatty acids (amphipathic, straight chain, even number, saturated/un saturated) Double bond (separated by methylene group, not adjacent/not conjugated, cis/trans isomers) Poly unsaturated fatty acids (essential fatty acids) + their function

Essential fatty acids Can't synthesized inside the body They are polyunsaturated fatty acids Can't synthesized inside the body The are required for normal growth. They are linoleic acid (ω-6), Linolenic (ω-3), arachidonic acid. They must be in diet for synthesis of other members of ω-3, ω-6.

Essential fatty acids Linoleic acid (18:2 Δ9,12 ω6) Constitutes about 60-80% of total fatty acid in dietary oils as corn oil, sunflower oil. Linolenic acid (18:3 Δ9,12 ,15 ω3): Present in small amount in plant oil, particularly in linseed oil

Arachidonic acid (20:4 Δ5,8,11,14 ω6) Present in (Arachis oil) Peanut oil. It may not be essential to take it in diet if there is an adequate supply of linoleic acid. It can be synthesized in side the body from linoleic.

Arachidonic acid 20 carbons contains 4 double bonds ------- more kinked U shape very important in fluidity of biological membrane

What about ω-7, ω-9, are they essential fatty acid??? They can be synthesized in side the body, so they are not essential fatty acids

Do you know others ω3 fatty acids? Eicosapentaenoic acid (20:5) Docosahexaenoic acid (22:6) Both of them present in fish oil (Salmon). They protect from cardiovascular diseases Why Eskimos have low susceptibility to heart diseases?????

The importance of essential fatty acid Synthesis of prostaglandins and thromboxanes (Eicosanoids) Enter in cell membrane structure Lower the cholesterol level Role of Linolenic acid in the formation of docosahexaenoic (DHA) acid (22:6 3), DHA is needed for the brain & retina (its deficiency leads to a condition called retinitis pigmentosa). Role in growth and development.

Characteristics of double bond Numbering of fatty acids Characteristics of Fatty acids fatty acids (Amphipathic, Even number, straight chain, double bond) Function of fatty acids (energy, fat soluble vitamins, thermal/ electerical insulator, cell membrane) Polyunsaturated fatty acids Function of Polyunsaturated fatty acid Characteristics of double bond Separated by methylene bridge Not adjacent/ not conjugated Cis/ trans isomers Comparison between cis/trans isomers Melting temp. ( low melting temp is in cis form unsaturated fatty acids, short/ medium chain fatty acids Numbering of fatty acids Δ delta numbering (from COOH) Δ1,Δ2,Δ3 GreeK lettering (from COOH) …..α, β,α Omega numbering (from CH3) …..ω1,ω2,ω3

Classification of lipids Substances associated with lipids ( polyprenoid compounds) Simple lipids Compound lipids Derived lipids

Triacylglycerol They are esters of alcohol glycerol and three fatty acids If the three fatty acids are the same-----Simple Triacylglycerol If the three fatty acids are not the same------Mixed Triacylglycerol Triacylglycerol may be fluid or soild …………….When?????

Function of triacylglycerol Main storage form of fat. Can be stored in large amount as it is hydrophobic It provides the body with high energy It acts as insulator for heat. It supports internal viscera.

Mixed lipids Phospholipids Glycolipid (Glycospingolipids) Glycero-phospholipids Sphingo-phospholipids (Sphingomylein)

Plasmalogen

Phosphatidic acid An Intermediate in the synthesis of TAG, phospholipid (parent compounds) is not common constituents in tissues.

Glycerophospholipids It contain glycerol + 2 fatty acids attached to C1,2 + phosphate group attached to C3+ base or alcohol Usually saturated fatty acid Usually unsaturated fatty acid Ethanol, choline, serine, inositol, glycerol

Types of Glycerophospholipids (3) (2) (1) Choline Serine or ethanolamine Phosphatidyl choline ( lecithin) Dipalmityl lecithin =lung surfactant Phosphatidyl serine/ ethanolamine (cephalins) They have role in blood coagulation

Types of phospholipids (5) (4) Stearic acid Arachidonic acid inositol Plasmalogens They resemble phospholipids, except: Have ether link in C1 not ester Alcohol in C1 Ethanolamine plasmalogen present in brain Phosphatidyl inositol Phosphatidyl inositol 4,5 bisphosphate has a role in signaling transduction

Types of phospholipids (6) (7) Cardiolipin (Diphosphatidyl glycerol) Present in mitochondrial memb. glycerol Phosphatidyl glycerol - Present in mitochondrial memb.

Types of phospholipids (8) lysolecithin Lysophospholipid (lysophosphatidyl choline) -is phospholipid with free OH in C2

Glycerophospholipids 1- Phosphatidyl choline (lecithin) e.g dipalmitoyl lecithin (lung surfactant). 2- phosphatidyl serine/ ethanolamine (cephalins) have a role in blood coagulation. both 1- 2 are the most of phospholipids in tissue 5- Phosphatidyl glycerol present in mitochondria. 6- Diphosphatidyl glycerol (cardiolipin) presents in mitochondrial membrane and had immunological properties 3- Phosphatidyl inositol e.g Phosphatidyl inositol 4,5 bisphosphate has a role in signal transduction and cell membrane 4-Plasmalogens e.g plasmalogens ethanolamine in brain (had ether link at C1+ and unsaturated alcohol at C1 7- Lysophospholipids: they are phosphoacylglycerol, metabolic intermediates of phospholipids ( no fatty acid in C2). 8- Phosphatidic acid is an intermediates of triacylglycerol & phospholipid synthesis. Not present in tissue structure.

Important Notes Most phospholipids contain more than one kind of fatty acids. Saturated fatty acid is attached to C1. While, unsaturated fatty acid is attached to C2 except in Dipalmityl lecithin Phospholipase A2 enzyme attacks C2 position

Did you remember 5 types of phospholipids? Of course……NO

Mixed lipids Phospholipids Glycolipid (Glycospingolipids) √ Glycero-phospholipids Sphingo-phospholipids Sphingomyelin √

Sphingomyelin Sphingosine = Serine+ fatty acid (palmitate) The backbone is sphingosine Sphingosine = Serine+ fatty acid (palmitate) Ceramide= Sphingosine+ fatty acid Sphingomyelin= ceramide + Phosphocholine Sphingomylein is present in cell membrane and myelinated nerve fiber.

Sphingomyelin Sphingomyelin= ceramide + Phosphocholine

Functions of phospholipids (1)Structural component of membranes (2) Enter in lipoprotein structure, which help in lipid transport in body Transport of triacylglycerol from liver to body, any defect lead to fatty liver (3) Solubilize cholesterol in bile, any defect lead to cholesterol stones

Special function of phospholipids Dipalmitoyl Phosphatidyl choline = Dipalmitoyl lecithin= Lung surfactant It contains palmitic acid at C1,2 It decrease the surface tension in the lung alveoli. So, it prevent adherence of the inner surfaces of the lung. It is synthesized around time of birth.

Lung surfactants (dipalmitoly lecithin) At, birth if decrease----- it leads to “RDS” respiratory distress syndrome

Phosphatidyl inositol 4,5 bisphosphate: Act as second messenger in signal transduction Acidic phospholipids: which have (-) net charge at physiological PH - Phosphatidyl serine, inositol, glycerol and cardiolipin They play a role in blood coagulation. Antibodies against acidic phospholipids recurrent thrombosis and recurrent fetal loss (antiphospholipids syndrome)

Mixed lipids Phospholipids Glycolipid (Glycospingolipids) Glycero-phospholipids Sphingomylein √ √

Glycolipids (glycosphingolipids) They are complex of lipids Ceramide + carbohydrate Sphingosine +fatty acid =N-acyl sphingosine Carbohydrate

Gangliosides Sulfatides Types of glycolipids Gangliosides Ceramide+ two or more monosaccharides+ one or more sialic acid (NANA) (N-acetyl neuraminic acid ) -ganglion cells of CNS -act as receptor or for cell- cell recognition Sulfatides galactocerebroside + sulfate Cerebrosides (ceramide hexosamide) ceramide is attached to monosaccharide unit by β-glycosidic bond Two types of cerebrosides Galactocerebrosides Present in brain & nervous tissue Glucocerebrosides Present in extra neural tissue

Remember All Glycolipids & Sphingomylein contain sphingosine All glycerophospholipids contain glycerol All Glycolipids & Sphingomylein contain sphingosine

Mention 4 diseases that are related to phospholipids abnormalities Mention 4 diseases that are related to phospholipids abnormalities? What are sphingolipids?

Steroids (Sterols) √ Are the compounds that have steroid nucleus. Steroid nucleus is composed of 4 rings identified by A-B-C-D, and formed of 19 carbons √

Cholesterol Is the major sterol in animal tissue Cholesterol has 27C OH- attached to C3 (amphipathic)

May be esterified with unsaturated fatty acid (cholesterol ester). Cholesterol ester is the storage form inside the cell Blood cholesterol is either in free form(1/3) or in ester form (2/3).

Cholesterol is the precursor of : Steroid hormones: sex hormones, glucocorticoids,mineralocorticoids Vitamin D3 Bile acids

Plant sterol is ergosterol is the precursor of Vit D2 Bacteria do not contain sterol