LIPIDS

PRASETYASTUTI

LIPIDS• Insoluble in water

• Soluble in non polar solvents : ether, CHCl3, benzene

• The lipids include : fats, oils, steroids, waxes

• Important dietary constituents because

- of their high energy value

- the fat - soluble vitamins

- the essential fatty acids contained in the fat of natural foods

• Serves as

• 1. an efficient source of energy directly and potentially when stored in adipose tissue

Serves as

1. an efficient source of energy directly and potentially when stored in adipose tissue2. A thermal insulator in the sub cutaneous tissues and around certain organs3. Non polar lipids act as electrical insulator

Lipoprotein ( combination of fat and protein ) are:

- important cellular constituents- occurring in the cell membrane in the mitochondria within the

cytoplasm- transporting lipids in the blood

CLASIFICATION1. Simple lipids: ester of fatty acids with various alcohols

a. Fats : ester of fatty acids with glycerol – Oil , a fat in the liquid stateb. Waxes : ester of fatty acids with higher molecular weight

monohydride alcohos

2. Complex lipids : ester of fatty acids containing groups in addition to an alcohol and a fatty acids

a. Phospholipids : lipids containing fatty acids, alcohol , a phosphoric acids residue frequently have nitrogen – containing bases and other substituent - glychophospholipids : the alcohol is glycerol

- sphingophospholipids : the alcohol is sphingosineb. Glycolipids : lipids containing a fatty acid, sphingosine,

carbohydrate

• C. Other complex lipids : sulfolipids, aminolipids , lipoproteins

• 3. Precursor and derived lipids

• Include : fatty acids, glycerol, steroids, alcohols in addition to glycerol and sterols, fatty aldehides and ketone bodies, hydrocarbons, lipid- soluble vitamins, and hormones

• Acylglycerols (glycerides)

• Cholesterol

• Cholesteryl esters

• -------------------------- neutral lipids because they are uncharged

• FATTY ACIDS- are aliphatic carboxylic acids

- occur mainly as :

• ester in natural fats and oils ( unesterified form)

• Usually straight-chain derivatives and contain an even number of carbon atoms because they are synthesized from two-carbon units

• free fatty acids

• Saturated acids end in – anoic ( octanoic acid)

• Contain no double bonds

• CH3 – COOH : the first member of the series

• - CH2 – is progressively added between the terminal CH3 – and – COOH groups

• Unsaturated acids end in – enoic ( octadecenoic acid (oleic acid)

• Contain one or more double bonds

• 1. Monounsaturated : contain one double bond

• 2. Poly unsaturated : contain >/ 2 double bond

• 3. Eicosanoid : derived from eicosa ( -20-C ) polyenoic fatty acids

• = Prostanoids :– Prostaglandin

– Prostasiklin

– Tromboxan

= Leukotrienes

= lipoxins

• Prostaglandins• Exist in every mammalian tissues

• Acting as local hormones

• Have important physiologic and pharmacologic activities.

• Synthesized in vivo by cyclization of the center of the carbon chain of 20 – carbon (eicosanoic) polyunsaturated fatty acids to form a cyclopentane ring

• Physical and physiologic properties of fatty acids • - the melting points of even – numbered- carbon fatty acids increase

with chain length and decrease according to unsaturation

• Triacylglycerol contaning all saturated fatty acids of 12 carbons or more is solid at body temperature

• If all three fatty acid residues are 18 :2, it is liquid to below O o C

• TRIACYLGLYCEROLS ( TRIGLYCERIDES)• - the main storage forms of fatty acids

• -esters of the alcohol glycerol and fatty acids.

• - in naturally occurring fats

• - the propotion of triacylglycerol molecule containing the same fatty acid residue in all three ester positions is very small.

• - nearly all mixed acylglycerols

• - if all three fatty acids represented by R were stearic acid : tristearin

• PHOSPHOLIPIDS the main lipid constituents of membranesinclude : 1. Phosphatidic acid and phosphatidylglycerol : intermediate

in synthesis of TG2. Phosphatidylcholine ( lecithins)- occur in cell membranes- represent a large proportion of the body’s store of choline(important in nervous transmission, as acetylcholine, and as

store of labile methyl groupsDipalmitoyl lecithin : - very effective surface-active agent - major constituent of the surfactant preventing adherence,

due to surface tension

3. Phosphatidylethanolamine (cephalin)

4. Phosphatidylinositol

- is a precursor of second messengers

- inositol as the stereoisomer, myoinositol

- Phosphatidylinositol 4,5 bisphosphate – is an important constituent of cell membrane phospholipids

– It is cleaved ---- diacylglycerol and inositol triphosphate ( act as internal signals or second messengers)

5. Phosphatidylserine

6. Lysophospholipids– Intermediates in the metabolism of phosphoglycerols

– Phosphoacylglycerols containing only one acyl radical ( lysophosphatidylcholin = lysolecithin, important in the metabolism and interconversion of phospholipids

7. Plasmalogens

- constitute as much as 10% of phospholipids of brain and muscle

- structurally resemble phosphatidylethanolamine

8. Sphingomyelins

- are found in large quantities in brain and nerve tissue.

- on hydrolysis, yield a fatty acud, phosphoric acid, choline, and a complex amino alcohol, sphingosine

-combination of sphingosine plus fatty acid is ceramide

Glycolipids (glycosphingolipids) Are important in nerve tissues and in the cell membrane Are widely distributed in every tissue of the body,

particularly in nervous tissue such as brain. Occur particularly in the outer leaflet of the plasma

membrane, where they contribute to cell surface carbohydrates

Glycosphingolipids :

– the major glycolipids found in animal tissues

– Contain ceramide and one or more sugars

Galactosylceramide :

• a major glycosphingolipid of brain and other nervous tissue

• Can be converted to sulfogalactosyl ceramide (sulfatide) is present in high amounts in myelin

Glucosylceramide :

• Predominant simple glycosphingolipid of extraneural tissues, in the brain in small amount

Gangliosides

• Are complex glycosylceramide that contain in addition one or more molecules of a siallic acid

• Neuraminic acid is the principal sialic acid found in human tissues

• Present in nervous tissues in high concentration

• The simplest ganglioside found in tissues is Gm3

• Gm3 contain ceramide, one molecule of glucose, one molecule of galactose and one molecule of NeuAc

• STEROIDSCholesterol

• Is widely distributed in all cells of the body, particularly in nervous tissue

• A major constituent of the plasma membrane & plasma lipoprotein

• Often found as cholesteryl ester

• Occurs in animal fat, not in plant fat

precursor :– The bile acids

– Adrenocortical hormones

– Sex hormones

– D. vitamins

– Cardiac glycosides

– Sitosterols

– Some alkaloids

ERGOSTEROL• A precursor vitamin D

• Occurs in plants and yeast

• When irradiated with UV light, it acquires antirachitic properties consequent to the opening of ring B

COPROSTEROL/COPROSTANOL

• Occurs in feces as a result of the reduction of the double bond of cholesterol between C5 and C6 by bacteria in the intestine

• POLYPRENOIDSNot steroidsAre synthesized like cholesterol, from five carbon isoprene

unitsInclude:* ubiquinone : a member of the respiratory chain in

mitochondria* dolicol : the long chain alcoholTake part in glycoprotein synthesis by transferring

carbohydrate residues to asparagine residues of the polypeptide

* rubber* camphor* vit. A, D, E, K and beta carotene :

• LIPID PEROXIDATION• Is a source of free radicals ( ROO., RO. OH.)

• Peroxidation lipids exposed to oxygen is responsible for

– Deterioration of food (rancidity)

– Damage to tissues in vivo ----• Cause : cancer

» Inflammatory diseases

» Atherosclerosis

» aging

The whole process of lipid peroxidation:

• 1. Initiation– ROOH + metal (n)+ ----- ROOo + metal (n-1)+ + H+

– Xo + RH ----- Ro + XH

2. Propagation

Ro + O2 ----- ROOo

ROOo + RH ----- ROOH + Ro

3. Termination

ROOo + ROOo ----- ROOR + O2

ROOo + Ro ----- ROOR

Ro + Ro ----- RR

• To control and reduce lipid peroxidation use antioxidants

• - propyl gallate

• Butylated hydroxyanisole (BHA)

• Butylated hydroxytoluene (BHT)

• Vitamin E (tocopherol) ---- lipid soluble– antioxidant at high PO2

• Urate

• Vitamin C

• Bata carotene , antioxidant at low PO2

Antioxidants fall into two classes• 1. Preventive antioxidants : reduce the rate of chain

initiation

• : catalase, DTPA, EDTA

• 2. Chain – breaking antioxidants ; interfere with chain propagation

• : phenol

• Superoxide dismutase : which acts in the aqueous phase to trap superoxide free radicals

• Urat and Vitamin E : which acts in the lipid phase to trap ROOo radicals

• Peroxidation is also catalyzed by : heme compounds

• And lipoxygenase

• Separated and identify lipids• I. Classic chemical procedures

– Crystallization

– Distillation

– Solvent extraction

• II. Chromatographic procedures– TLC : separation of the various lipid classes

– GLC : separation of the individual fatty acids

Amphipathic • Lipids are insoluble in water( contain a predominance of

non polar= hydrocarbon)

• Fatty acids, phospholipids, sphingolipid, bile salt, cholesterol contain polar groups

• Part of the molecule is hydrophobic, or water in soluble and part is hydrophilic, or water soluble === amphipathic

• They become oriented at oil- water interface with the polar group in the water phase and nonpolar group in the oil phase.

• A bilayer of such amphipathic lipids has been regarded as a basic structure in biologic membranes