LIPID CHEMISTRY

DR ROHINI C SANE

PROFESSOR

DEPARTMENT OF BIOCHEMISTRY

D Y PATIL MEDICAL COLLEGE EBENE

PROPERTIES OF ESSENTIAL FATTY ACIDS (EFA )

• HYDROGENATION (UNSATURATED --- SATURATED FATTY ACIDS(SOLIDIFICATION )

• LINOLENIC ACID (3 = BONDS)+ 2HLINOLEIC ACID (2 =BONDS )

• LINOLEIC ACID (2 =BONDS )+2 HOLEIC ACID (1 = BOND )

• OLEIC ACID (1 = BOND ) +2 HSTEARIC ACID (NO = BOND)—SATURATED FATTY ACID

PROPERTIES OF ESSENTIAL FATTY ACIDS (EFA )

• NOT SYNTHESIZED IN BODY

• TO BE SUPPLIED IN DIET (ESSENTIAL)---HUMAN BODY DOSE NOT HAVE ENZYMES TO ADD DOUBLE BOND BEYOND POSITION 9

• LINOLEIC ACID18 ,2,(9,12)

• LINOLENIC ACID 18,3,(912,15)

• ARACHIDONIC ACID 20 4,(5,8,11,14)

• ARACHIDONIC ACID -- LINOLENIC ACID (PARTIALLY SYNTHESIZED IN HUMAN BODY)

PROPERTIES OF FATTY ACIDS (EFA )

• II HYDROGENATION

• UNSATURATED FATTY ACIDS + 2 HALOGEN ATOMS >HALOGENATED DERIVATIVE (eg DI IDOOLEIC ACD)

III MELTING POINT

• SHORT & MEDIUM CHAIN ---LOW MELTING POINT

• LONG CHAIN ----HIGH MELTING POINT

• INCREASE IN CHAIN LENGTH ---MELTING POINT &BOILING POINT INCREASES

• STEARIC ACID (18C)---69οC, OLEIC ACID (1= BOND ) 15 ο C

• INCREASE IN CHAIN LENGTH----SOLUBILTY DECREASES (BILE SALTS NEEDED FOR ABSORPTION )

•

PROPERTIES OF FATTY ACIDS (EFA )

IV SALT FORMATION WITH ALKALI

• CH3COOH + NaOH -CH3COONa+ H2O

• LONG CHAIN FATTY ACID + NaOH -SOAP (INSOLUBLE)

• CALCIUM /MAGNESIUM SALTS---- >GREASE

PROPERTIES OF FATTY ACIDS (EFA )

V ESTER FORMATION

• FATTY ACIDS +ALCOHOL(GLYCEROL ) -- ESTER

• (GLYCEROL )+ FATTY ACIDS --MONOACYL GLYCEROL

• MONOACYL GLYCEROL +FATTY ACIDS ----DIACYL GLYCEROL

• DIACYL GLYCEROL + FATTY ACIDS ----->TRIACYL GLYCEROL

Isomerization of unsaturated fatty acids

Geometrical isomerization

• I Acyl groups are on same side of double bond –cis isomers –oleic acid –less stable

• II I Acyl groups are on opposite side of double bond—trans isomers –Elaidic acid—more stable

• MCQ ---CIS ISOMERS PACK THE MEMBRANE STRUCTURE.

• Naturally occurring unsaturated fatty acids exist in cis forms.

•

OXIDATION OF FATTY ACIDS

• SATURATED FATTY ACIDS -----BETA OXIDATION---ATP

• UNSATURATED FATTY ACIDS ---AUTOOXIDATION (REACTIVE DOUBLE BONDS )

• PEROXIDES

• ENEDIOLS

• EPIOXIDES

• ALDEHYDES

ANTIOXIDANTS PREVENT OXIDATION OF FATTY ACIDS

• BHA ---BUTYLATED HYDROXY ANISOL

• BHT ----BUTYLATED HYDROXY TOLUENE

• VITAMIN E

• PROPYL GALLATE

HYDROQUINONE

FUNCTIONS OF ESSENTIAL FATTY ACIDS (EFA )

• MEMBRANE STRUCTURE

• CHOLESTEROL TRANSPORT

• FORMATION OF LIPOPROTEINS

• PREVENTION OF FATTY LIVER

• FORMATION OF PROSTAGLANDINS PROSTACYCLINS,THROMBOXANES

• HYDROXY FATTY ACIDS –BETA HYDROXY BUTYRIC ACID –KETONE BODY—ENERGY SOURCE IN STARVATION

• CHAULMOOGIC ACID ACID –CYCLIC FATTY ACID—CYCLO PENTENYL RING –LEPROSY TREATMENT

• EICOSONOIDS –eg –PROSTAGLANDINS ,LEUKOTRIENES ,THROMBOXANES

DEFICIENCY MANIFESTIONS OF ESSENTIAL FATTY ACIDS

TOAD SKIN DISEASE ----PHRYNODERMA

POOR WOUND HEALING

HORNY ERUPTIONS ON POSTERIOR & LATERAL PARTS OF LIMB,ON BACK ,BUTTOCK

TOAD SKIN DISEASE---PHRYNODERMA

PROSTAGLANDINS• CYCLIC COMPOUNDS (POLY ENOIC FATTY ACIDS )

• DERIVATIVES OF UNSATURATED FATTY ACIDS –ARACHIDONIC ACID 20C ,4 =BONDS –POSITIONS OF= BONDS --5,8,11,14

FUNCTIONS OF PROSTAGLANDINS• PREVENT INFLAMMATION

• LOWER BLOOD PRESSURE

• TREATMENT OF GASRTIC ULCERS

• INHIBIT PLATELET AGGREGATION

• PROMOTE CLOTTING PROCESS

• TREATMENT OF ASTHMA & CONGENITAL HEART DISEASE

PROSTAGLANDINS SITE OF FORMATION FUNCTIONS

PGE2 MOST TISSUE VASODIALATATIONSMOOTH MUSCLE RELAXATIONLABOUR INDUCER –UTERINE CONTRACTIONTREATMENT OF HYPER TENTION

PGF2ALPHA MOST TISSUE VASOCONSTRICTIONBRONCHOCONSTRICTIONSMOOTH MUSCLE CONTRACTIONMEDICAL TERMINATIONOF PREGNANCY –UTERINE CONTRACTION

PROSTAGLANDINS SITE OF FORMATION FUNCTIONS

PGI2 ENDOTHELIAL VESSELS VASODIALATATION

THROMBOXANES PLATELETS INCREASE PLATELET AGGREGATIONTHROMBOSISVASO CONSTRICTIONSMOBALIZATION OF INTRACELLULAR CALCIUMBRONCO CONSTICTION

LEUKOTRIENES

A4,B4.C4,D4,E4

LEUCOCYTESPLATELETSMAST CELLS HEART CELLSVASCULAR TISSUE

CHEMOTAXISMOVEMENT OF CELL RESPONSE TO STIMULIBRONCO CONSTICTIONVASO CONSTRICTIONSC4,D4,E4—ALLERGIC REACTIONS--FATAL

CHEMISTY OF CHOLESTEROL

• CHOLE =GREEK WORD ---MEANS BILE ,ISOLATED FROM BILE.SOLID ALCOHOL FROM BILE ---ANIMAL STEROL

• MOLECULAR FORMULA C27H46O

• OH AT C3---AMPHILIC ,FORMS ESTER WITH FATTY ACIDS –CHOLESTEROL ESTERS

• DOUBLE BOND BETWEEN C5= C6

• OCCURRENCE ---CELL MEMBRANE,BILE, LIPOPROTEINS

Cholesterol: is a sterol (with 8 carbons at C17,= bet 5&6)

Sterols: are steroids with 8-10 carbon atoms in the AMPHIPHATIC

side chain at C-17 & OH at C-3

•Cholesterol is the major sterol in animal tissues

•Plant sterols as B-sitosterol are poorly absorbed by

humans, it blocks the absorption of dietary cholesterol

•Dietary intake of plant steroid esters (trans fatty acid –free

margarine ) helps in reduction of plasma cholesterol

Structure of cholesterol and its ester.

Plant sterols block the absorption of dietary cholesterol.

FUNCTIONS OF CHOLESTEROL• CELL MEMBRANE SRUCTURE FORMATION&FUNCTIONS

• LIPOPROTEIIN SYNTHESIS

• FATTY ACID TRANSPORT FOR BETA OXIDATION

• SYNTHESIS OF VITAMIN D

• SYNTHESIS OF STEROID HORMONES

• Glucocorticoid ---cortisol

• Minerocorticoid---Aldosterone

• Sex hormones----Progesterone//estradiol/Testosterone

• BILE SALTS SYNTHESIS

• POOR CONDUCTOR OF HEAT& ELECTICITY –INSULATING COVER—BRAIN &MYELIN SHEATH

CHOLESTROL BIOSYNTHESIS

• Animal Sterol

• 70kg/body weight------2gm /kg -----140 gm cholesterol/70kg body weight

• Amphiphatic---hydrophilic& hydrophobic regions

• 1 gm/day synthesis

• Organs involved in synthesis---- Cytosol /microsomes of adrenal cortex

• Liver/intestine/testes/ovaries/skin/adrenal cortex

Synthesis of cholesterol• SITES----CYTOSOL OF ALL TISSUES AND MICROSOMES

• REDUCING EUIVALENTS-----NADPH

• ENERGY---------ATP

• CARBON SKELETON------1,3,5,7,9,11,13,15,17,18,19,22,24,26

PROPERTIES OF CHOESTEROL• YELLOWISH CRYSTALLINE SOLID

• MICROSCOPIC NOTCHED APPEARANCE

• INSOLUBLE IN WATER

• SOLUBLE IN CARBON TETRA CHLORIDE,CHLOROFORM,ETHERS ,BENZENE

• TEST FOR DETECTION ---ZAKS TEST –FERRIC CHLORIDE +H2SO4—BROWN COLOR

•

CLINICAL SIGNIFICANCE OF CHOLESTEROL ESTIMATION

• Normal levels 150-200 mg/dl (adult )

• New born -----100 mg /dl

• Women < men ( Decrease in estrogen--------decrease cholesterol)

• ESTIMATION …….Liebermann Burchard reactions

• CHOLESTEROL + ACETIC UNHYDRIDE -------H2SO4 ---GREEN COMPLEX

• TOTAL CHOLESTROL = HDL+ LDL+VLDL

• TG /5= VLDL

• AFTER THE PPTATION OF LDL & VLDL BY PEG

• LDL CHOLESTEROL = Total cholesterol – ( HDL + VLDL)

• = Total cholesterol – ( HDL + TG/5)

• LDL CHOLESTEROL -----70-200 mg/dl

• HDL CHOLESTEROL -------30-60 mg/dl (increase in HDL cholesterol is beneficial…..> /decrease in HDL harmful ….. CHD ------ATHEROSCLROSIS

• INCREASE IN CHOLESTROL ………CHD

CLINICAL SIGNIFICANCE OF CHOLESTEROL ESTIMATION

• HYPERCHOLESTEROLEMIA > 200 mg/dl

• Diabetes Mellitus ------increase availability of acetyl CoA

• Hypothyroid ( myxedema)…….decrease HDL receptors on Hepatocytes

• Obstructive Jaundice -------obstruction in excretion of cholesterol through bile

• Nephrotic syndrome----increase globulins -----increase in plasmsa lipoproteins

• Hypercholesterolemia----atherosclerosis ----CHD -----POSITIVE correlation of LDL--------NEGATIVE correlation HDL

•

CONTROL OF HYPERCHOLESTEROLEMIA

• PUFA –LCAT----CHOLESTEROL TRANSPORT ---EXCRETION OF CHOLE---DECREASE IN CHOLESTEROL

• (PUFA---COTTON SEED OIL,SOYABEAN OIL,CORN OIL,FISH OIL,SUN FLOWER OIL)

• (B) DIETARY FIBRES –DECREASE IN CHOLESTEROL ABSORPTION

• (C) AVOID CARBOHYDRATE DIET

• (D) DRUGS ---LOVASTATIN