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Properties of Lipids Greasy to touch, leaves a permanent oily stain on

paper;

Lighter than water Soluble in organic solvent, insoluble in water When pure, colorless with bland odor and taste Yellow color in fat is due to carotene

(provitamin A) When heated strongly, undergoes decomposition

forming acrid flammable vapors and whenignited, they burn with a sooty flame.

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LIPIDS Important dietary constituents

High energy value

Contains fat-soluble vitamins and essential fattyacids

Essential Fatty Acids (EFAs)

Are necessary fats that humans cannot synthesize,and must be obtained through diet.

Are long-chain polyunsaturated fatty acids derivedfrom linolenic, linoleic, and oleic acids

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Biomedical ImportanceFatFatstored in adipose tissue serves as thermal

insulator in the subcutaneous tissues andaround certain organs;

NonpolarNonpolar lipidslipids act as electrical insulator,allowing rapid propagation of depolarization

waves along myelinated nerves; LipoproteinsLipoproteins occur in both cell membrane and

mitochondria, and also serve to transport lipidin the blood.

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Major Roles of

Biological Lipids They serve as structural components ofbiological membranes;

They provide energy reserves, predominantlyin the form of triacylglycerols;

Both lipids and lipid derivatives serve as

vitamins and hormones; and Lipophilic bile acids aid in lipid

solubilization.

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IMPORTANCE OF LIPID

BIOCHEMISTRY

Obesity, Diabetes mellitus,

Atherosclerosis Role of various polyunsaturated fattyacids in nutrition and health

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Classification of Lipids Simple lipid

Ester of fatty acid and _______

Fats/fixed oil - ester of fatty acid and _______

Triglycerides - esters of three molecules of fatty acidsplus one molecule of glycerol

Found in adipose tissue, butterfat, lard, suet, fishoils, olive oil, corn oil

Waxes - ester of fatty acid and _______

beeswax, head oil of sperm whale, cerumen,carnauba oil, and lanolin

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Compound Lipid Esters of fatty acid, alcohol and another

compound. A. PHOSPHOLIPIDS

Fatty acid and alcohol plus a _______residue;

Frequently have nitrogen-containing basesand other substituents(glycerophospholipids, the alcohol is______; sphingophospholipids, thealcohol is __________).

Classification of Lipids

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B. GLYCOLIPIDS Glycosphingolipids

fatty acid and sphingosine pluscarbohydrate.

C. OTHER COMPLEX LIPIDS sulfolipids and aminolipids lipoproteins

Classification of Lipids

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Are aliphatic carboxylic acids Occur mainly as esters of natural fats and oils

but do occur in the unesterified form as free fattyacids ( transport form found in the plasma)

In natural fats, they are usually straight-chainderivatives containing an even number of carbon

atoms. SATURATED no double bonds UNSATURATED containing one or more doublebonds

Fatty Acids

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Fatty Acids Saturated fatty acids: CnH2nO2 Unsaturated fatty acids: C

n

H2n - (2x #db)

O2

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Structure of Fatty Acids

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Structure of Fatty Acids

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Structure of Fatty Acids

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Geometric isomerism in

unsaturated fatty acid cis

The acyl chain are on

the same side of thebond

Oleic acid

trans The acyl chain is on the

opposite side

Elaidic acid

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NOMENCLATURE Named after the corresponding hydrocarbons

with the same number and arrangement of

carbon atoms, with-oic being substituted for thefinal e :

anoicanoic saturated acid ends (e.g.,octanoic acid)

enoicenoic unsaturated acids with double bonds(e.g., octadecenoic acid)

C atoms are numbered from the carboxyl C as C-1

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Adjacent to carboxyl C as 2, 3 and 4 are alsoknown as , , and carbons, respectively

Terminal methyl C is known as or n-carbon

is used conventionally to indicate the numberand position of the double bond, eg., 9, double

bond between C-9 and C-10

NOMENCLATURE

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COMMON

NAME

# OF C

ATOMS

Acetic 2 Major end product of carbohydrate

fermentation by rumen organism

Butyric 4 In certain fats in small amounts (butter)

End product of carbohydrate fermentationby rumen organisms

Valeric 5

Caproic 6

Lauric 12 Spermaceti, cinnamon, palm kernel, coconut

oils, laurels, butterMyristic 14 Nutmeg, palm kernel, coconut oils, myrtles,

butter

Palmitic 16 Common in all animal and plant

Stearic 18

SATURATED FATTY ACIDS

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UNSATURATED FATTY ACIDS

MONOUNSATURATEDMONOUNSATURATED (Monoethenoid,monoenoic) acids containing double bond

POLYUNSATURATEDPOLYUNSATURATED (polyethenoid, polyenoic)acids containing two or more double bonds

EICOSANOIDSEICOSANOIDS

Derived from eicosa (20 carbon) polyenoic fatty acids

Arachidonic acid is the major precursors

Prostanoids

Leukotrienes (LTs )

Lipoxins (LXs)

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PROSTANOIDS

Are part of a family of biologically active lipidsderived from the twenty-carbon essential fattyacids or eicosanoidseicosanoids;

Relates to the products of the cyclooxygenasepathway

Prostanoic acid as the central structural element

Three main groups Prostaglandins (PGs)

Prostacyclins (PGIs)

Thromboxanes (TXs)

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PROSTAglandins

Acts as local hormones

Synthesized from eicosanoic polyunsaturated

fatty acids (arachidonic acid) to formcyclopentane ring

PG1, PG2, and PG3 numbers are based on thedouble bonds in the side chain

The letter component identifies the functionalgroups of the cyclopentane ring

PGE keto group in 9 position

PGF hydroxyl group in 9 position

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THROMBOXANES

Cyclopentane ringinterrupted with an

oxygen atom; The two major

thromboxanes are

thromboxane A2 andthromboxane B2

Its role is in clot formation(thrombosis)

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PHYSICAL and PHYSIOLOGIC

PROPERTIES OF FATTY ACIDS MELTING POINT of even numbered carbon fatty

acids; increases with chain length

decreases according to unsaturation TRIACYLGLYCEROL containing three saturated

fatty acids of 12 C or more is solid at bodytemperature 18:2 fatty residues are liquid at body temperature to

below 0C MEMBRANE LIPIDS must be fluid at all

environmental conditions More unsaturated than storage lipids

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TRIACYLGLYCEROLS

(TRIGLYCERIDES) Main storage forms of fatty acids

They are formed by esterification of glycerol withthree fatty acids

Depending on the content of unsaturated fattyacids, triglycerides can be solids (fats) or liquids

(oils) Oils have highly unsaturated fatty acid chains andare liquid at room temperature

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Main lipid constituents

of membrane Derivatives of

phosphatidic acid

Phosphate is esterifiedwith the OH of asuitable alcohol

Phosphatidic acid intermediate in thesynthesis oftriacylglycerols

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PHOSPHATIDYLCHOLINE

(Lecithin) Phosphoacylglycerol

containing choline

Most abundant phospholipidsof the cell membrane andrepresent a large proportion ofthe bodys store ofcholine

CHOLINECHOLINE important innervous transmission, asacetylcholine, and as a store oflabile methyl group

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DIPALMITOYL LECITHIN

Major constituent of the surfactant preventingadherence, due to surface tension, of the innersurfaces of the lungs.

Absence from the lungs of premature infantscauses respiratory distress syndrome

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PHOSPHATIDYLETHANOLAMINE

(Cephalin) Ethanolamine replaces choline A lipid found in biological

membranes Cephalin is found particularlyin nervous tissue such as thewhite matter of brain, nerves,neural tissue, and in spinalcord

Cephalin is the principalphospholipid in bacteria.

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PHOSPHATIDYLINOSITOL

Precursor of second messenger

Inositol is present as stereoisomer, myoinositol

Phosphatidylinositol 4,5-biphosphate importantconstituent of the cell membrane phospholipidsand cleaved into diacylglycerol and inositol

triphosphate (internal signals or secondmessenger)

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CARDIOLIPIN bisphosphatidyl glycerol

Is an important component of the inner

mitochondrial membrane, where it constitutesabout 20% of the total lipid

It serves as an insulator and stabilizes theactivity of protein complexes important to the

electron transport chain

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LYSOPHOSPHOLIPIDSAre intermediates in the metabolism of

phosphoglycerols

Important in the metabolism andinterconversions of phospholipids(lysophosphatidylcholine)

Found in oxidized lipoproteins and canpromote atheroschlerosis

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PLASMALOGENS

10% of the phospholipidsof the brain and muscle

Resemblephosphatidylethanolamine(ether linked)

Alkyl radical is an

unsaturated alcohol Choline, serine or inositol

---- may be substituted forethanolamine

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SPHINGOMYELINS

Found in large quantities in brain and nervetissues

Yields fatty acid, phosphoric acid, choline, anda complex amino alcohol, sphingosine

SPHINGOSINE

(the atoms in red are derived from glycerol)

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CERAMIDE

Sphingosine plus amino acid

Structure found in glycosphingolipids

"n" indicates any fatty acidmay be N-acetylated at this

position

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GLYCOLIPIDS

(GLYCOSPHINGOLIPIDS) Distributed in every tissue of the body

Nervous tissues (brain)

Plasma membrane cell surface carbohydrates

Glycosphingolipids

Major glycolipids in animal tissues

Ceramide + sugar GALACTOSYLCERAMIDE

Major sphingolipid of brain & other nervoustissue, C24 fatty acids

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GANGLIOSIDES Are complex glycosphingolipids derived from

glucosylceramide that contain in addition one ormore molecules of a sialic acid

NEURAMINIC ACID principal sialic acidfound in human tissues.

GM3 contains ceramide, one molecule ofglucose, one molecule of galactose and onemolecule of NeuAc The simplest gangliosides in tissues

GLYCOLIPIDS

(GLYCOSPHINGOLIPIDS)

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CHOLESTEROL

Associated with atherosclerosis & heart disease Biochemical significance

Precursor of bile acids, adrenocortical hormones, sexhormones, Vit. D, cardiac glycosides, sitosterols andalkaloids

Major constituent of the plasma membrane and ofplasma lipoproteins

Cholesteryl ester OH at 3 position is esterified with long chain fatty

acid Occurs in animals but not in bacteria

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POLYPRENOIDS

Not steroids, but synthesized like cholesterol

UBIQUINONE- participates in respiratory chain

in mitochondrion DOLICHOL - takes part in glycoprotein

synthesis by transferring carbohydrate residues

to asparagine residues of polypeptide ISOPRENOID rubber, camphor, fat soluble-Vit A, D, E & K and -carotene (provitamin A)

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LIPID PEROXIDATION

Lipids exposed to oxygen (Auto-oxidation)

A chain reaction providing a continuous supply

of free radicals Effects of peroxidation include:

deterioration of food (rancidity)

damage of tissue (cancer, inflammation,atheroschlerosis and aging) caused by free radicalscontaining methylene-interrupted double bonds

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PEROXIDATION

Catalyzed in vivo by heme compounds andby lipoxygenases (platelets andleukocytes)

Other products of auto-oxidation (orenzymatic oxidation) of physiologic

importance include; Oxysterols formed from cholesterol

Isoprostanes - prostanoids

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CLASSES OF ANTIOXIDANTS

i. Preventive antioxidants reduce the rate ofchain initiation

Catalases and Peroxidases - gluthathione peroxidase (reacts with ROOH)

Selenium

EDTA, DTPA (Chelators of metal ions)

ii. Chain-breaking antioxidants interfere withchain propagation

Superoxide dismutase trap superoxide free radicals

Urate

Vitamin E lipid phase trap ROO radicals

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AMPHIPHATIC LIPIDS

Contain predominantly nonpolar groups plus apolar group

Molecule is partly hydrophobic and hydrophilic Include fatty acids, phospholipids,

sphingolipids, bile salts, and cholesterol

Oriented at oil:water interfaces with the polargroup in water phase and the nonpolar group inthe oil phase

Basic structure of biologic membranes (bilayer)

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MICELLESMICELLES Formed when critical concentration

of amphiphatic lipids is present in

aqueous medium LIPOSOMESLIPOSOMES Formed by sonicating an

amphiphatic lipid in an aqueousmedium

Useful as carriers of drugs in

circulation, targeted to specificorgans, eg, in cancer therapy Also used for gene transfer into

vascular cells Carriers for topical and

transdermal delivery of drugs andcosmetics

AMPHIPHATIC LIPIDS

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Source of

fatty acid

Bodys main

fuel reserve

1

2

3

Acetoacetate and 3-

hydroxybutyrate important

fuels in prolonged fasting

Triacylglycerols

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Citric acid

cycle

Triacylglycerols

(fats)

Fatty acids

Acetyl CoA

CO2

Cholesterol

Steroids

Ketone bodies

Carbohydrates

Amino acids Ketogenesis

Cholesterologenesis

Steroidogenesis

Lip

olysis

Esterif

ication

Lipogenesis

-oxida

tion

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