Lipids

Are heterogeneous group of compounds (fats, oils, steroids, waxes and related compounds), that are related more by their physical than by their chemical properties. Common properties
(1)Relatively insoluble in water (2) Soluble in non-polar solvents

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 when ignited, they burn with a sooty flame.

LIPIDS
Important dietary constituents
High energy value Contains fat-soluble vitamins and essential fatty acids Essential Fatty Acids (EFAs)
Are necessary fats that humans cannot synthesize, and must be obtained through diet. Are long-chain polyunsaturated fatty acids derived from linolenic, linoleic, and oleic acids

Biomedical Importance
Fat stored in adipose tissue serves as thermal
insulator in the subcutaneous tissues and around certain organs; Nonpolar lipids act as electrical insulator, allowing rapid propagation of depolarization waves along myelinated nerves; Lipoproteins occur in both cell membrane and mitochondria, and also serve to transport lipid in the blood.

Major Roles of Biological Lipids

They serve as structural components of biological membranes; They provide energy reserves, predominantly in the form of triacylglycerols; Both lipids and lipid derivatives serve as vitamins and hormones; and Lipophilic bile acids aid in lipid solubilization.

IMPORTANCE OF LIPID BIOCHEMISTRY

Obesity, Diabetes mellitus, Atherosclerosis Role of various polyunsaturated fatty acids in nutrition and health

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 acids plus one molecule of glycerol Found in adipose tissue, butterfat, lard, suet, fish oils, olive oil, corn oil

Waxes - ester of fatty acid and _______

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

Classification of Lipids
Compound Lipid
Esters of fatty acid, alcohol and another compound. A. PHOSPHOLIPIDS Fatty acid and alcohol plus a _______ residue; Frequently have nitrogen-containing bases and other substituents (glycerophospholipids, the alcohol is ______; sphingophospholipids, the alcohol is __________).

Classification of Lipids
B. GLYCOLIPIDS Glycosphingolipids
fatty acid and sphingosine plus carbohydrate.

C. OTHER COMPLEX LIPIDS sulfolipids and aminolipids lipoproteins

Derived Lipid product of simple and compound lipid upon hydrolysis.

Fatty acids
occur in plant and animal foods also exhibit in complex forms with other substances obtained from hydrolysis of fats usually contains an even number of carbon atoms and are straight chain derivatives

Glycerol Steroids Other alcohols Fatty aldehydes Ketone bodies Hydrocarbons, Lipidsoluble vitamins Hormones * Acylglycerols, cholesterol, and
cholesteryl ester are uncharged, so are termed

NEUTRAL LIPIDS

Fatty Acids
Are aliphatic carboxylic acids Occur mainly as esters of natural fats and oils but do occur in the unesterified form as free fatty acids ( transport form found in the plasma) In natural fats, they are usually straight-chain derivatives containing an even number of carbon atoms.
SATURATED no double bonds UNSATURATED containing one or more double bonds

Fatty Acids
Saturated fatty acids: CnH2nO2 Unsaturated fatty acids: CnH2n - (2x #db) O2

Structure of Fatty Acids

Structure of Fatty Acids

Structure of Fatty Acids

Geometric isomerism in unsaturated fatty acid

cis
The acyl chain are on the same side of the bond Oleic acid

trans
The acyl chain is on the opposite side Elaidic acid

NOMENCLATURE
Named after the corresponding hydrocarbons with the same number and arrangement of carbon atoms, with-oic being substituted for the final e :
anoic saturated acid ends (e.g.,octanoic acid) enoic unsaturated acids with double bonds (e.g., octadecenoic acid)

C atoms are numbered from the carboxyl C as C1

NOMENCLATURE
Adjacent to carboxyl C as 2, 3 and 4 are also known as , , and carbons, respectively Terminal methyl C is known as or n-carbon is used conventionally to indicate the number and position of the double bond, eg., 9, double bond between C-9 and C-10

SATURATED FATTY ACIDS

COMMON NAME # OF C ATOMS

Acetic
Butyric

2
4

Major end product of carbohydrate fermentation by rumen organism

In

Valeric
Caproic Lauric

5
6 12

certain fats in small amounts (butter) End product of carbohydrate fermentation by rumen organisms Spermaceti, cinnamon, palm kernel, coconut oils, laurels, butter

Myristic
Palmitic

14
16

Nutmeg, palm kernel, coconut oils, myrtles, butter

Common in all animal and plant

Stearic

18

UNSATURATED FATTY ACIDS

MONOUNSATURATED (Monoethenoid,
monoenoic) acids containing double bond POLYUNSATURATED (polyethenoid, polyenoic) acids containing two or more double bonds EICOSANOIDS Derived from eicosa (20 carbon) polyenoic fatty acids Arachidonic acid is the major precursors Prostanoids Leukotrienes (LTs ) Lipoxins (LXs)

PROSTANOIDS
Are part of a family of biologically active lipids derived from the twenty-carbon essential fatty acids or eicosanoids; Relates to the products of the cyclooxygenase pathway Prostanoic acid as the central structural element Three main groups
Prostaglandins (PGs) Prostacyclins (PGIs) Thromboxanes (TXs)

PROSTAglandins
Acts as local hormones Synthesized from eicosanoic polyunsaturated fatty acids (arachidonic acid) to form cyclopentane ring PG1, PG2, and PG3 numbers are based on the double bonds in the side chain The letter component identifies the functional groups of the cyclopentane ring
PGE keto group in 9 position PGF hydroxyl group in 9 position

THROMBOXANES
Cyclopentane ring interrupted with an oxygen atom; The two major thromboxanes are thromboxane A2 and thromboxane B2 Its role is in clot formation (thrombosis)

LEUKOTRIENES and LIPOXINS

Formed via the lipooxygenase pathway Has three (leukotrienes) to four (lipoxins) conjugated double bonds Leukotrienes - a proinflammatory agents and causes bronchoconstriction, thus play a part in asthma
Common leukotriene inhibitors
Zyflo Zileuton Accolate Zarfirlukast Singulair - Montelukast

PHYSICAL and PHYSIOLOGIC PROPERTIES OF FATTY ACIDS

MELTING POINT of even numbered carbon fatty acids; TRIACYLGLYCEROL containing three saturated fatty acids of 12 C or more is solid at body temperature MEMBRANE LIPIDS must be fluid at all environmental conditions
More unsaturated than storage lipids increases with chain length decreases according to unsaturation

18:2 fatty residues are liquid at body temperature to below 0C

TRIACYLGLYCEROLS (TRIGLYCERIDES)
Main storage forms of fatty acids They are formed by esterification of glycerol with three fatty acids Depending on the content of unsaturated fatty acids, triglycerides can be solids (fats) or liquids (oils)
Oils have highly unsaturated fatty acid chains and are liquid at room temperature

 Main lipid constituents of membrane Derivatives of phosphatidic acid Phosphate is esterified with the OH of a suitable alcohol Phosphatidic acid intermediate in the synthesis of triacylglycerols

PHOSPHATIDYLCHOLINE (Lecithin)
Phosphoacylglycerol containing choline Most abundant phospholipids of the cell membrane and represent a large proportion of the bodys store of choline CHOLINE important in nervous transmission, as acetylcholine, and as a store of labile methyl group

DIPALMITOYL LECITHIN
Major constituent of the surfactant preventing adherence, due to surface tension, of the inner surfaces of the lungs. Absence from the lungs of premature infants causes respiratory distress syndrome

PHOSPHATIDYLETHANOLAMINE (Cephalin)
Ethanolamine replaces choline A lipid found in biological membranes Cephalin is found particularly in nervous tissue such as the white matter of brain, nerves, neural tissue, and in spinal cord Cephalin is the principal phospholipid in bacteria.

PHOSPHATIDYLSERINE
Serine replaces choline Found in most tissues US-FDA qualified claim states that;
"Consumption of phosphatidylserine may reduce the risk of dementia in the elderly" and; "Consumption of phosphatidylserine may reduce the risk of cognitive dysfunction in the elderly".

PHOSPHATIDYLINOSITOL
Precursor of second messenger Inositol is present as stereoisomer, myoinositol Phosphatidylinositol 4,5-biphosphate important constituent of the cell membrane phospholipids and cleaved into diacylglycerol and inositol triphosphate (internal signals or second messenger)

CARDIOLIPIN
bisphosphatidyl glycerol Is an important component of the inner mitochondrial membrane, where it constitutes about 20% of the total lipid It serves as an insulator and stabilizes the activity of protein complexes important to the electron transport chain

LYSOPHOSPHOLIPIDS
Are intermediates in the metabolism of phosphoglycerols Important in the metabolism and interconversions of phospholipids (lysophosphatidylcholine) Found in oxidized lipoproteins and can promote atheroschlerosis

PLASMALOGENS
10% of the phospholipids of the brain and muscle Resemble phosphatidylethanolamine (ether linked) Alkyl radical is an unsaturated alcohol Choline, serine or inositol ---- may be substituted for ethanolamine

SPHINGOMYELINS
Found in large quantities in brain and nerve tissues Yields fatty acid, phosphoric acid, choline, and a complex amino alcohol, sphingosine

SPHINGOSINE (the atoms in red are derived from glycerol)

CERAMIDE
Sphingosine plus amino acid Structure found in glycosphingolipids

"n" indicates any fatty acid may be N-acetylated at this position

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 nervous tissue, C24 fatty acids

GLYCOLIPIDS (GLYCOSPHINGOLIPIDS)
GANGLIOSIDES
Are complex glycosphingolipids derived from glucosylceramide that contain in addition one or more molecules of a sialic acid

NEURAMINIC ACID principal sialic acid found in human tissues. GM3 contains ceramide, one molecule of glucose, one molecule of galactose and one molecule of NeuAc
The simplest gangliosides in tissues

STEROIDS
Phenanthrene rings

Cyclopentane ring

This nucleus, partially or completely hydrogenated, is generally substituted by methyl groups at C10 and C13. A chemical group (ketone, hydroxyl...) or an alkyl side-chain may also be present at C17

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Steroids
The carbon skeleton of steroids is bent to form 4 fused rings
Cholesterol

Cholesterol is the base steroid from which your body produces other steroids

Estrogen Testosterone

Estrogen & testosterone are also steroids

CHOLESTEROL
Associated with atherosclerosis & heart disease Biochemical significance
Precursor of bile acids, adrenocortical hormones, sex hormones, Vit. D, cardiac glycosides, sitosterols and alkaloids

Major constituent of the plasma membrane and of plasma lipoproteins Cholesteryl ester
OH at 3 position is esterified with long chain fatty acid Occurs in animals but not in bacteria

ERGOSTEROL
Precursor of vitamin D2 Occurs in plants and yeast It is turned into viosterol by UV light, and is then converted into ergocalciferol (a form of Vitamin D) Acquires antirachitic properties when irradiated with UV light A component of fungal cell membranes, serving the same function that cholesterol serves in animal cells

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 solubleVit A, D, E & K and -carotene (provitamin A)

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 radicals containing methylene-interrupted double bonds

PEROXIDATION
Catalyzed in vivo by heme compounds and by lipoxygenases (platelets and leukocytes) Other products of auto-oxidation (or enzymatic oxidation) of physiologic importance include;
Oxysterols formed from cholesterol Isoprostanes - prostanoids

ANTIOXIDANTS
Control and reduce lipid peroxidation Antioxidants for food are propyl gallate, BHA, BHT Naturally occuring antioxidants include;
Vitamin E (tocopherol) is lipid soluble Vitamin C and urate are water soluble Beta-carotene

CLASSES OF ANTIOXIDANTS
i. Preventive antioxidants reduce the rate of chain initiation
Catalases and Peroxidases - gluthathione peroxidase (reacts with ROOH) Selenium EDTA, DTPA (Chelators of metal ions)

ii. Chain-breaking antioxidants interfere with chain propagation

Superoxide dismutase trap superoxide free radicals Urate Vitamin E lipid phase trap ROO radicals

AMPHIPHATIC LIPIDS
Contain predominantly nonpolar groups plus a polar group Molecule is partly hydrophobic and hydrophilic Include fatty acids, phospholipids, sphingolipids, bile salts, and cholesterol Oriented at oil:water interfaces with the polar group in water phase and the nonpolar group in the oil phase Basic structure of biologic membranes (bilayer)

AMPHIPHATIC LIPIDS
MICELLES
Formed when critical concentration of amphiphatic lipids is present in aqueous medium Formed by sonicating an amphiphatic lipid in an aqueous medium Useful as carriers of drugs in circulation, targeted to specific organs, eg, in cancer therapy Also used for gene transfer into vascular cells Carriers for topical and transdermal delivery of drugs and cosmetics

LIPOSOMES

Bodys main fuel reserve

Source of fatty acid

2

3 1

Acetoacetate and 3hydroxybutyrate important fuels in prolonged fasting

Triacylglycerols (fats)
Esterification Lipolysis

Steroids
Steroidogenesis

Fatty acids
-oxidation Lipogenesis

Cholesterol
Cholesterologenesis

Carbohydrates

Acetyl CoA
Amino acids

Ketogenesis
CO2

Citric acid cycle

Ketone bodies