•Classification1. Storage lipids.2. Structural lipids in membranes.3. Lipids as signals, cofactors and pigments.

Storage Lipids• Fatty acids are hydrocarbon derivatives.

-C4 to C36.-Saturation.-Nomenclature.-Physical properties.

• Triacylglycerols.-Simple vs. complex triglycerides.-Functions: provide stored energy and insulation.

• Waxes.-Functions: serve as energy stores and water repellents

Biochemistry of Lipids:Objectives

- Recognize the features and Functions of different classes of “Lipids”- Understand the nomenclature and the physical properties of fatty acids and the relation

of these properties to the saturation state of the fatty acids. - Recognize the structure and the function of different classes polar lipids.- Recognize the structure most popular examples for each class of lipids.- Understand the role lipids as pigments, signals and cofactors, knowing different examples

Structural Lipids• Types of membrane lipids:

1. Glycerophospholipids:-Phosphatidic acid.

2. Sphingolipids:-Sphingosine.

3. Sterols: -Steroid nucleus.-Functions.

Lipids as signals, cofactors and pigments

• Phosphatidylinositols act as intracellular signals.Eicosanoids carry messages to nearby cells.

-Prostaglandins.-Thromboxanes.-Leukotrienes.

• Steroid hormones carry messages between tissues.• Vitamins A. • Vitamins D. • Vitamins E.• Vitamins K.

ReferencesChap. 11 of Lehninger

Defined on the basis of solubility.Lipids: heterogeneous group of water insoluble (hydrophobic) organic

molecules, they are chemically diverse compound but have one feature: water insoluble

Many distinct chemical species in a “lipid fraction”

Functions

-The biological functions of lipids are divers as their chemistryLipids perform three biological functions:

1. Lipids in form of a bilayer are essential components of biological membranes.

2. Lipids containing hydrocarbon side chains serve as energy stores.

3. Many intra-and intercellular signaling events involve lipid molecules.

Lipids

1. Storage lipidsTriglycerides, Waxes and Fatty acids.Fats and oils are stored forms of energy and are derivatives of fatty acids.

2. Structural lipids in membranesGlycerophospholipids, Sphingolipids, Sterols. are major structural elements in biological membranes

3. Lipids as signals, cofactors and pigments.These lipids presents in small quantities but play crucial roles-Phosphatidylinositols, Eicosanoids

- Prostaglandins.- Thromboxanes.- Leukotrienes.- Steroid hormones carry messages between tissues.- Vitamins A and D are hormone precursors.- Vitamins E and K are oxidation-reduction cofactors.

Lipid Classification

Fats and oils are derivatives of Fatty acids.

Fatty acids (F.A) are carboxylic acids with long hydrocarbon chain ranging from 4-36 carbon atom 16- and 18-C long are most abundant. -Even number of carbons, 16, 18… the odd are also present but rare.

-the hydrocarbon chain can be fully saturated (without double bonds), or with one, two or three double bonds (cis-configuration only)- usually they are unbranched, some cases have methyl, hydroxyl, or three-carbon ring as branch

NomenclatureNumbered from carboxyl endspecify the chain length and the number of double bonds separated by colonPalmitic acid is saturated F. A with 16 C atoms 16:0Stearic acid 18:0

Linoleic acid 18:2(Δ 9,12)Arachodonic acids 20:4 (Δ 5,8,11,14)

Storage Lipids

The position of double bond should be specified superscript numbers following the Δ (delta)Oleic acid 18:1(Δ 9)Linoleic acid 18:2(Δ 9,12)Linolenic acid 18:3(Δ 9,12,15)the location of double bonds is 9=10; 12=13; 15=16

Arachodonic acids 20:4 (Δ 5,8,11,14)

-the polyunsaturated F. A are never conjugated, the double bond is separated by methyl group

1

9

Longer the fatty acid chain -Higher the melting temperature ( i.e. more solid at room temp) More double bonds -lower the melting temperature ( i.e. more liquid at room temperature )

Omega Fatty acids

-Essential F.ALinoleic (18:2Δ9,12)

ω6Linolenic (18:3Δ9,12,15)

ω3Arachidonic (20:4Δ5,8,11,14)

ω6

Physical properties of F. A and the compounds containing them are largely determined by the length and degree of unsaturation of the hydrocarbon chainSolubility:The non-polar hydrocarbon chain account for the poor solubility of F. A in water Lauric acid 12:0 Mr 200 sol. In water 0.063 mg/gGlucose M.wt 180 water sol. Is 1.1mg/g

*The carboxyl group is polar and this accounts for the slight solubility of short chain fatty acid in water

*The longer the fatty acid acyl and fewer the double bonds, the lower is the solubility in water

Melting pointsmelting points are strongly influenced by the length and degree of un-saturation -at R.T the saturated F. A with length chain 12-24 have waxy consistency while the unsaturated F. A are liquid

Physical properties of fatty acids

fully saturated molecule free rotation around each C-C

This gives the hydrocarbon chain great freedom and flexibility

adopt the most stable conformation which is the fully extended form in which the steric hindrance of neighboring atoms is minimized

The molecules can pack together tightly in nearly crystalline arrays. So the Vander Waal interaction and the hydrophobic interaction are maximizedHigh thermal energy required to disorder (melt) these highly ordered F.A molecules higher melting points

Saturated chains pack tightly and form more rigid, organized aggregates

In the unsaturated F. A the cis configuration double bond forces a kink (bend) in the hydrocarbon chain

F.A with one or more kinks cannot pack together as tightly as fully saturated F.A and their interactions are weaker So the unsaturated F.As take less thermal energy to disorder these poorly ordered arrays of unsaturated F.As they have lower melting points

Unsaturated chains bend and pack in a less ordered way, with greater potential for motion

Triacylglycerols or Triglycerides

Simple triacylglycerols: containing the same kind of F.A in all three positions of glycerolSimple triacylglycerols of 18:0 = tristearin16:0 tripalmitin18:1 trioleinMixed triacylglycerols: different fatty acids esterified with glycerol

triglycerides are non-polar and hydrophobic molecules(the polar groups of both glycerol and F. A are are linked in ester linkage non-polar molecule )

Fatty acid triesters of glycerol Most contain two or three different types of fatty acid residues

Fats and oils* Plant oils are usually richer in unsaturated fatty acids residues than animal fats* Fats and oils are complex mixtures of mixed triacylglycerols and simple triacylglycerols*Triacylglycerols can be found in most eukaryotic cell as oily droplets in the aqueous cytosol serving as metabolic fuel *In vertebrates specialized cells called Adipocytes(fat cell) store amounts of triglycerides as fat droplets that fill the cell. Triglycerides also stored as oil in the seeds of many types of plants .*Adipocytes contain lipases catalysis the hydrolysis of stored triglycerides releasing F.A for export to sites where they can be used as fuel. *Two advantages for using the triglycerides as stored fuel rather than polysaccharides as glycogen and starch:1- the carbon atoms of F.A are more reduced than that of carbohydrates oxidation of triglycerides yields more than twice as much energy (gm/gm) as the oxidation of CHO2- triglycerides are hydrophobic unhydrated, the organism that carries fat as fuel does not have to carry the extra weight of water of hydration that is associated with stored polysaccharides (2gm water/1gm polysaccharides

Fats function as energy reservoirs in animalsThe fat content of normal humans allows them to survive starvation for 2 or 3 monthsWhile human store of glycogen can supply only for one day but carbohydrates are quick sources for metabolic energy because of water solubility Fat stores: skin, abdominal cavity and mammary gland Triacylglycerols

Triacylglycerols function to insulate: protect the body from the outer environments

Vegetable oils: are composed of Triacylglycerols with unsaturated fatty acids liquid at room tem.Vegetable oils can be into solid by catalytic hydrogenation which reduce the double bonds to single bonds.

* Exposure of the lipid rich food to oxygen for long time may spoil and the lipid is said to be Rancid. Rancidity results from the cleavage of double bond in unsaturated F. A that produce aldehyde and carboxylic acid with low M.wtbad smell

Waxes serve as energy store and water repellents

Biological waxes are esters of long chain (C14-C36) saturated and unsaturated fatty acid with long chain alcohol (C16-C30) melting points about 60-100 ºC

Function of Biological waxes-Skin glands of some vertebrates secret waxes to protect hair and skin to keep it pliable, lubricated and water proofLeaves of many tropical plants are coated by waxes to prevent excessive evaporation of water and protect against parasitesWaxes can be used in pharmaceutical industries in lotions, ointments and

polishes

Polar vs. Nonpolarlipids•Non-Polar Lipids –Energy storage •Polar lipids are the basis of Bilayers

Biological membranesfeature: double layer of lipid act as barrier to the passage of polar molecules and ions.Amphipathic: one end of the molecule is hydrophobic and the other is hydrophilic

The hydrophobic interactions between molecules and the hydrophilic interactions with water direct their packing into sheets called membrane bilayer

Glycerophospholipids are the major lipid component of biological membranes-amphiphilic molecules with non-polaraliphatic tails and polar phosphoryl-X heads

Glycerophospholipids

Phosphoglycerides: two F. A are attached in ester linkage to the first and second carbons of glycerol and a highly charged group is attached through a phosphodiester linkage to the third carbon

Glycerophospholipids“Phospholipids”

*some animal tissues are rich in ether lipids: one of the acyl group is attached to glycerol in ether rather than ester linkage. The ether-linked chain can be maybe saturated alkyl ether lipid or may unsaturated alkene-ether linked chain

Platelet activating factor: released from leukocyte (basophiles) and stimulate platelet aggregation and the release of serotonin

Plasmalogen: ether linked alkene found in heart tissue, 50% of the phosphlipid in the heart is Plasmalogen

SphingolipidsSphingolipids are major membrane components, with polar head and non-polar tail • They are derivatives of the C18 amino alcohol sphingosine• The double bond in sphingosine is trans • C1, C2, C3 of sphingosine molecule are structurally similar to the three carbons of glycerol in phospholipids• N-acyl fatty acid derivatives of sphingosine are known as ceramides• Ceramides are the parent compounds of the more abundant sphingolipids.

General structure of Sphingolipids, if X is H, the compound is Ceramide

Sphingomyelins: contain phosphocholine or phosphoethanolamine as their polar group and so can be classified as phospholipids.Sphingomyelins resemble phosphotidylcholines in their general properties and three-dimensional structure and in having no net charge on their head groups The myelin sheath that surrounds and insulates nerve cells is rich in Sphingomyelins

Glycosphingolipids (Glycolipids): occur largely in the outer face of plasma membrane, have one or more sugars connected directly to the –OH at C1 of the ceramide moiety and can be classifiedA- Neutral Glycolipids (uncharged) no net charge at pH=71- Cerebroside: single sugar linked to ceramide usually Glucose or Galactose2- Globoside: Di, tri or tetrasaccharide linked to ceramide as Glu, Gal, N-acetly galactosamineB- Ganglioside: the most complex glycolipid, have oligosaccharide as their polar head groups and one or more residues of Sialic acid Ganglioside are primarily components of membranes on cell surfaces and constitute 6% of brain lipidsSphingolipids: act as a site of biological recognition, act as receptors for hormones and glycoproteins

3-Sterols Structural lipids present in the membranes of some eukaryotic cells. Characterized by the steroid nucleus consisting of four fused rings three rings with 6 C atoms and one ring with 5 C atoms, the steroid nucleus is relatively rigid and planar Cholesterol is the major sterol in animal tissues and it is amphipathic with a polar head (the –OH group), and the non-polar body is the steroid nucleus Similar sterols are present in eukaryotes: Stigmasterol plantsErgosterol fungi

Functions- Membrane constituents

- Precursors of different product with vital biological activities (steroidal hormones that regulate the gene expression)

- Bile acids are derivatives of cholesterol that act as emulsifying agent in the intestine

Lipids as Signals, cofactors and pigments Group of lipids present in small amounts play various essential function- Have active roles in metabolic processes as metabolite and messenger- Potent signals and hormones carried in the blood from one tissue to others- Intracellular messengers generated to response to outer signal - Can function as cofactors- Pigments- Fat soluble vitamins

Phosphotidyl inositol: act as intracellular signals: Intracellular messengers are released from the Phosphotidyl inositol in response to extra cellular signals interacting with receptors on the outer surface of the membrane

* Signals act through a series of steps

IP3

Eicosanoids: are paracrine hormones; substances that act only on site cells near the point of synthesis instead of being transported in the blood to act on other cells or tissues. Eicosanoids are derived from membrane lipids and mainly from Arachodonic acid [20:4(Δ5,8,11,14 ]1- Prostaglandins•C20 compounds • Five carbon ring• affect a wide range of cellular and tissue function•Act at low concentration and are involved in the production of pain and fever, regulation of blood pressure, blood coagulation and reproduction •Produced and used locally• Regulate the synthesis of the intracellular messenger (cAMP) which mediate the action of different hormones. -Stimulate the contraction of smooth muscle in uterus -Affect the blood flow-Elevate the body temperature and mediate the inflammation and pain2- Thromboxanes:Six-memebred ring containing an ether, produced by the platelets (thrombocytes) and play role in formation of the blood clots 3- Leukotriens: contain conjugated double bonds, found in the leukocytes, powerful biological signals, induce contraction of muscles lining the airways of the lung. Over production cause asthmatic attack

Aspirin and NSAIDs•Aspirin inhibits the synthesis of prostaglandins from arachidonicacid by chemically modifying a serine residue of the enzyme PGH2 synthase (Cyclo oxygenase enzyme) preventing arachidonicacid from reaching the enzyme active site •Non-steroidal anti-inflammatory drugs (NSAIDs) (ibuprofen and acetaminophen) non covalently bind to PGH2 synthase, also preventing arachidonicacid from reaching the enzyme active site

•Leukotrienes have been implicated in various inflammatory and hypersensitivity disorders (such as asthma). They are synthesized from arachidonateby an aspirin-insensitive pathway Steroidal anti-inflammatory drugPrednisone and prednisolone inhibit the phospholipase A2 that release the Arachodinic acid from the phospholipids in the membrane the synthesis of all eicosanoid will be inhibited

Steroidal HormonesSteroids: oxidized form of the sterol, with the steroid nucleus but lack the alkyl chain-More polar than cholesterol -Move through the blood on proteins carriers from site of production to target tissue.Then bind to their receptors

enter the nucleus affect the gene expression and metabolism-male and female sex hormones (Testosterone and estradiaol) -adrenal cortex hormone: cortisol and aldesterone-Prednisone and prednisoloneare synthetic steroids

Lipid Soluble Vitamins Vitamins: Compounds that are essential to the health of human and other animalsand most of the vitamins cannot be synthesized by endogenously Two classes of Vitaminsa. Fat soluble vitaminsb. Water soluble vitamin, Vit B and Vit C

Vitamin DA group of structurally related compounds that play a role in the regulation of calcium and phosphorus metabolism

-the most abundant form in the circulatory system is vitamin D3 (Cholecalciferol) which is formed in the skin from 7-dehydrocholesterol

-Vit D3 is converted into the active form in two steps the first at the liver and the second at the kidney

-The active form of vit D3 (1,25-dihydroxycholecalciferol) regulates the Ca uptake in the intestine and Ca levels in the kidney

-Deficiency of Vit D3 defective bone formation and Rickets disease

Vitamin D activation

Vitamin A (Retinol)•Vit A with its precursors and its derivatives function as hormones and as the visual pigments in the eye• β-carotene: yellow pigments in the carrotRetinoic acid : is a derivative of Vit A and can regulate gene expression in the development of epithelial tissue (skin)

Vitamin E•Vitamin E is a group of compounds of similar structure; the most active is α-tocopherol- Associates with cell membranes, lipids, lipoproteins in the blood- An antioxidant; traps HOO• and ROO• radicals formed as a result of oxidation by O2 of unsaturated hydrocarbon chains in membrane phospholipids

protect the unsaturated F.A from oxidation and prevent oxidative damage to membrane lipid-Deficiency of Vit E : Rough skin, muscular weakness and sterility

•Blood clot factor: undergo a cycle of oxidation reduction during the formation of the active prothrombine•Different forms, most common n=8•Functions in blood clotting

Vitamin K

Vit K1 (Phylloquinone)

The End