Lipids

Lipids are non-polar (hydrophobic) organic compounds, insoluble in water, soluble in organic solvents (ether, acetone, carbontetrachloride). They contain carbon, hydrogen, and oxygen; sometimes nitrogen and phosphorus. In most cases they yield fatty acids on hydrolysis.They take place in lipid and plant metabolism.

What are Lipids?

Fatty acids

Fatty acids (FAs) consist of hydrocarbon chain with a carboxylic acid at one end straight-chain organic acids Most naturally occurring fatty acids have an even number of carbon atoms

They can be saturated and unsaturated.

Unsaturated fatty acids have lower melting points than saturated fatty acid.

Fatty acids

Monounsaturated FAs one double bond

Polyunsaturated FAs many double bonds

Eicosanoids (include prostaglandins, leukotriens, prostacyclins, thromboxanes)Double bonds in fatty acids are usually

in the cis configuration.

Linoleic acid is a nutritionally essential fatty acid. that must be ingested by humans and other animals because the body requires it but cannot synthesize it.

It is found in large conc. in corn, peanut, soyabean oils but not in olive oil.

Absence of linoleic acid by infants weight loss and ezema.

Linoleic acid

Classification of lipids according to their structures

Classification of lipids according to their structuresSimple lipids esters of FAs (FAT, OIL, WAX) [One or two chemical identities)

Hydrolysis of a simple lipid Simple lipid + H2Ofatty acid + alcohol

If the alcohol is glycerol (FAT or OIL)

If the alcohol is a monohydric alcohol WAX

Hydrolysis of complex lipids more fatty acids + alcohol +other compound

Phospholipid + H2O (hydrolysis) FA + alcohol + phosphorus + nitrogen compound.

Phospholipids phosphoglyceride or phosphosphingoside

Glycolipid + H2O (hydrolysis) FA +a carbohydrate + sphingosine

Precursor lipids compounds resulting from hydrolysis of simple or complex lipids (FA, sphingosine)

Derived lipids lipids which are formed due to the transformation of fatty acids (Prostaglandins, Fat-soluble vitamins)

Classification of lipids according to their structures

Fats and oilsFats with a melting point below room temperature are called oils.

Iodine numberThe iodine number of a fat or an oil is the umber of grams of iodine that will react with the double bond present in 100 g of fat or oil

Higher iodine number higher degree of unsaturation

Generally iodine number of animal fats < iodine number of vegetable oils

Iodine number of fats <70

Iodine number of oils > 70

Some uses of lipids in the body Fats serve as fuel.

Fats serve as reserve supply of food and energy.

Fats are stored in special adipose tissues and serve as a protector for vital organs.

Fats act as heat insulators.

Some lipids allow rapid propagation of electrical signals.

Physical properties White or yellowish solid or liquids

Pure fats and oils are odorless and tasteless. Over a period of time they become rancid and develop an unpleasant odor and tatse.

Lighter than water.

When shaken with water temporarily emulsion.

Emulsion can made permanent by addition of emulsifying agent such soap.

Fats and oils must be emulsified before they can be digested.

Chemical reactionsHydrolysis

3. Enzyme

Saponification

Hydrogenation

In Practice not all double bonds are hydrogenated.Hydrogenation lowers the iodine number.

Acrolein test: Test for fats or oils which contain glycerol

Glycerol (KHSO4) (heat)Acrolein (strong odor)

Rancidity: unpleasant odor or taste developed when fats stand at room temperature for a short period of time.Rancidity is due to hydrolysis and oxidation reactions.Oxidation of double bonds short chain aldehydes and acids bad odor and taste (Antioxidant Vit. E and C.)Fats + Water in butter (in presence of microorganisms)hydrolysis of fats Butyric acid disagreeable odor.Fats and foods containing fats have to be covered and stored in the refrigerator

Cleansing action of soaps

CH3-(CH2)16-COONa (Sodium stearate)

Non-Polar Polar

Hydrophopic Hydrophilic

Micelle

Mechanical Washing causes the oil to break down into small dropsSoap emulsifies then the oil and prevents it from coalescing.Soap acts also as surfactant lowers surface tension

Detergents

Synthetic compounds used as cleansing agents.

Soaps do not work in hard water insoluble Ca and Mg salts

Detergents work also in hard water

Soaps (alkaline); Detergents (neutral) Detergents can be used on silks and wool; Sops not.

Detergents: Sodium salts if long chain alcohol sulfates

Example: Sodium laurylsulfate

C12H23OH + H2SO4 C11H23CH2OSO3H + H2O

C11H23CH2OSO3H + NaOH C11H23CH2OSO3Na + H2O

Complex lipids and cell Membranes: an overview

Some functions of membranes (40-50% lipids; 50-60% Proteins)1. Mechanical support.2. Seperate contents of the cells from the environment3. Structural support for proteins (pumps; receptors)

Biochemistry IISelf aggregation of lipids

Introduction to lipids

Polar end (hydrophilic end)

non-polar endhydrophobic end)

Glycerophospholipids

Glycerophospholipids (phosphoglycerides), are common constituents of cellular membranes.They have a glycerol backbone.Hydroxyls at C1 & C2 are esterified to fatty acids.

C OHH

CH2OH

CH2OH

glycerol

An ester forms when a hydroxyl reacts with a carboxylic acid, with loss of H2O.

Formation of an ester:

O O

R'OH + HO-C-R" R'-O-C-R'' + H2O

Phosphatidate

In phosphatidate: fatty acids are esterified to hydroxyls on C1 & C2 the C3 hydroxyl is esterified to Pi.

O P O

O

O

H2C

CH

H2C

OCR1

O O C

O

R2

phosphatidate

In most glycerophospholipids (phosphoglycerides), Pi is in turn esterified to OH of a polar head group (X): e.g., serine, choline, ethanolamine, glycerol, or inositol. The 2 fatty acids tend to be non-identical. They may differ in length and/or the presence/absence of double bonds.

O P O

O

O

H2C

CH

H2C

OCR1

O O C

O

R2

X

glycerophospholipid

Phosphatidylinositol, with inositol as polar head group, is one glycerophospholipid. In addition to being a membrane lipid, phosphatidylinositol has roles in cell signaling.

O P

O

O

H2C

CH

H2C

OCR1

O O C

O

R2

OH

H

OH

H

H

OHH

OH

H

O

H OH

phosphatidyl- inositol

Phosphatidylcholine, with choline as polar head group, is another glycerophospholipid.

It is a common membrane lipid.

O P O

O

O

H 2 C

C H

H 2 C

OCR 1

O O C

O

R 2

C H 2 C H 2 N C H 3

C H 3

C H 3

+

p h o sp h a tid y lc h o lin e

O P O

O

O

H2C

CH

H2C

OCR1

O O C

O

R2

X

glycerophospholipid

Each glycerophospholipidincludes a polar region:

glycerol, carbonyl O of fatty acids, Pi, & the polar head group (X)

non-polar hydrocarbon tails of fatty acids (R1, R2).

Structure of phospholipids

Sphingosine may be reversibly phosphorylated to produce the signal molecule sphingosine-1-phosphate. Other derivatives of sphingosine are commonly found as constituents of biological membranes.

H2CHC

OH

CH

N+ CH

C

CH2

CH3

H

H3

OH

( )12

sphingosine

Sphingolipids are derivatives of the lipid sphingosine, which has a long hydrocarbon tail, and a polar domain that includes an amino group.

sphingosine-1-P

H2CHC

O

CH

N+ CH

C

CH2

CH3

H

H3

OH

( )12

P O

O

O

In the more complex sphingolipids, a polar “head group" is connected to the terminal hydroxyl of the sphingosine moiety of the ceramide.

H2CHC

OH

CH

N+ CH

C

CH2

CH3

H

H3

OH

( )12

sphingosineH2C

HC

OH

CH

NH CH

C

CH2

CH3

H

OH

( )12

C

R

O

ceramide

The amino group of sphingosine can form an amide bond with a fatty acid carboxyl, to yield a ceramide.

Sphingomyelin, with a phosphocholine head group, is similar in size and shape to the glycerophospholipid phosphatidyl choline.

Sphingomyelin has a phosphocholine or phosphethanolamine head group. Sphingomyelins are common constituent of plasma membranes.

H2CHC

O

CH

NH CH

C

CH2

CH3

H

OH

( )12

C

R

O

PO O

OH2C

H2CN+

CH3

H3C

CH3

Sphingomyelin

phosphocholine

sphingosine

fatty acid

Cholesterol is largely hydrophobic.

But it has one polar group, a hydroxyl, making it amphipathic.

C holesterolH O

Cholesterol, an important constituent of cell membranes, has a rigid ring system and a short branched hydrocarbon tail.

cholesterol PDB 1N83

Structural features of cholesterol (Chol) and cholesteryl esters (Chol-esters)

CholesterolFour fused hydrocarbon rings (A, B, C, and D, called the "steroid nucleus"C8 branched hydrocarbon chain attached to C17Hydroxyl group at C-3 Double bond between C-5 and C-6 Sterols: Steroids with 8 to 10 C in sides chain and hydroxyl group at C-3 Cholesterol does not occur in plantsCholesteryl estersMost plasma cholesterol is in an esterified form.More hydrophobic than CholNot in membranes

Cholesterolin membrane

Cholesterol inserts into bilayer membranes with its hydroxyl group oriented toward the aqueous phase & its hydrophobic ring system adjacent to fatty acid chains of phospholipids.

The OH group of cholesterol forms hydrogen bonds with polar phospholipid head groups.

C holesterolH O

Two strategies by which phase changes of membrane lipids are avoided: Cholesterol is abundant in membranes, such as

plasma membranes, that include many lipids with long-chain saturated fatty acids. In the absence of cholesterol, such membranes would crystallize at physiological temperatures.

The inner mitochondrial membrane lacks cholesterol, but includes many phospholipids whose fatty acids have one or more double bonds, which lower the melting point to below physiological temperature.

Biochemistry IIMembrane lipids / Cholesterol Introduction to

lipids

Testosterone, the male sex hormone, is produced in the testes. Estradiol, one of the female sex hormones, is produced in the ovaries and placenta. Cortisol and aldosterone are hormones synthesized in the cortex of the adrenal gland; they regulate glucose metabolism and salt excretion.Prednisolone and prednisone are synthetic steroids used as antiinflammatory agents.

• Anabolic steroids (Athletes)TestosteroneIncrease of body mass, strengthSide effects (men) liver cancer, impotenceHypercholesterolemiaBreast growthSide effects (women) increased amount of

body hairVoice deepeningMenstrual irregularities

Biochemistry IIMembrane lipids / Cholesterol

Introduction to lipids

AtherosclerosisForm of ateriosclerosis resulting from the

deposition of lipids, primarily TAGs, and Chol, from the blood stream

Chol. is the larger threatWe have to reduce lipid intakeUnstaurated fish and vegetable oil Loweing of

Chol levelNormal Chol level = 200-220 mg/dlElevated Chol level should be cotrolled by dietIn extreme cases cholesterol lowering drungs

(pravastatin, lovastatin)

GM2

Sphingomyelin

Glycosphingolipids differ from sphingomyelin in that they do not contain phosphate.The polar head function is provided by a monosaccharide or oligosaccharide attached directly to the ceramide by an o-glycosidic bond.

Structure Of glycosphingolipids

The simplest neutral (uncharged) glycosphingolipids are the cerebrosides (ceramide + galactose or ceramide + glucose).They serves primarily as an intermediate in the synthesis and degradation of the more complex glycosphingolipids).The cerebroside are found predominantly in the brain and peripheral nervous tissue.Ceramide oligosaccharides (or globosides) are produced by attaching additional monosaccharides (including GalNAc).

Neutral glycosphingolipidsO

O HO

O H

OO

O H

OO H

H O

H O(C H2)1 2 C

HN (C H2)1 6 C H3

O

O H

Lactosylceramide (Gal- b 1,4-Glc- b 1,1'-Cer)

globo-

GalNAc- b 1,3-Gal- a1,4-

OH

O

O H

N H A c

H O

H OO

O H

OO

O H

Galactosylceramide

H OO H

O

O H

O

( C H 2 ) 1 2 C H 3

H N ( C H 2 ) 1 6 C H 3

O H

O H

Glucosylceramide

H OO H

O

O H

O

( C H 2 ) 1 2 C H 3

H N ( C H 2 ) 1 6 C H 3

O H

H O

O O

Eicosanoids participate in many processes in the body:Inflammatory response that occurs after infection or injury with symptoms such as pain, swelling, and fever. An exaggerated or inappropriate expression of the normal inflammatory response may occur in individuals who have allergic or hypersensitivity reactionsContraction of smooth muscles (particularly in the intestine and uterus)Increase in the excretion of water and sodium by the kidneyRegulation of blood pressureRegulation of bronchoconstriction and bronchodilation (modulators)

Functions of the Eicosanoids

Biosynthesis of the Eicosanoids

Cyclooxygenase Pathway: Synthesis of the Prostaglandins and Thromboxanes

1. Synthesis of PGH2

Oxidative cyclization of free arachidonic acid by prostaglandin endo-peroxide synthase PGH2 !!!!

PGH2!!!! variety of prostaglandins and thromboxanesProstaglandin endoperoxide synthase-2 activities (COX and peroxidase)

2 isoenzymes (COX1 and COX2) [2 O2 molecules]COX1: (in most tissues): maintenance of healthy gastric tissue, renal homeostasis, and platelet aggregation.COX2: (inducible in a limited number of tissues) in response to products of activated immune and inflammatory cells.

Cyclooxygenase Pathway: Synthesis of the Prostaglandins and Thromboxanes

2. Inhibition of prostaglandin synthesis Cortisol (a steroidal anti-inflammatory agentinhibition of PLA2, COX2 but not COX1.NSAIDS (nonsteroidal anti-inflammatory agents (e.g. Aspirin) inhibition of COX1 and COX2 damage to the stomach and the kidneys, and impaired clotting of blood, is the basis of aspirin's toxicity.Specific inhibitors for COX2 (for example, celecoxib1) are designed to reduce pathologic inflammatory processes while maintaining the physiologic functions of COX2.