Chemistry of phospholipidsDR ROHINI C SANE

PROFESSOR

DEPARTMENT OF BIOCHEMISTRY

DR D Y PATIL MEDICAL COLLEGE

EBENE

CLASSIFICATION OF PHOSPHOLIPIDS

• FATTY ACIDS +ALCOHOL+NITRGEN BASE+ PHOSPHARIC ACID

• I GLYCEROPHOSPHOLIPIDS ----OR PHOSPHOGLYCERIDE---GLYCEROL /ALCOHOL

• II SPHINGOPHOSPHOLIPIDS----SPHINGOMYELINS----ALCOHOL –SPHINGOSINE

GLYCEROPHOSPHOLIPIDS

• GLYCEROPHOSPHOLIPIDS---MAJOR LIPID IN BIOLOGICAL MEMBRANE

• GLYCEROL -3-P IS esterified at C1& C2.

• C1---SATURATED FATTY ACID

• C2 ---UNSATURATED FATTY ACID

• TYPE –1—PHOSPHATIDIC ACID

• INTERMEDIADE IN SYNTHESIS OF TRIGLYCEROL

& PHOSPHOLIPIDS

GLYCEROPHOSPHOLIPIDSTYPE 2 –LECITHIN—PHOSPOTIDYL CHOLINE

FATTY ACID +GLYCEROL )CHOLINE

• MOST ABUNDANT GROUP OF PHOSPHOLIPID IN CELL MEMBRANE

• PHOSPHATIDIC ACID + CHOLINE

• STORAGE OF BODY”CHOLINE (DONAR OF METHYL GROU IN METHYLATION REACTIONS )

• CHOLINE –ACETYL CHOLINE NERVE IMPULSE TRANSMISSION

• LYSOLECITHIN –REMOVAL OF FATTY ACIDS FROM C1 OR C2 OF

LECTHINDIPALMITOL LECITHIN –MAINTAIN SURFACE TENSION—ADHERENCE OF INNER SURFACE OF LUNGS

DEFICIENCY –RESPIRATORY DISTRESS SYNDROME IN INFANTS

GLYCEROPHOSPHOLIPIDSTYPE III CEPHALIN ---(PHOSPHOTIDYL ETHANOLAMINE)

FATTY ACIDS +GLYCEROL +PHOSPHARIC ACID -ETHANOLAMINE(NITROGEN BASE )

• CLOTTING FACTOR III THROMBOPLASTIN –CEPHALIN

• FUNCTION HELPS IN CLOTTING OF BLOOD

TYPE IV PHOSPHOTIDYL INOSITOL

FATTY ACIDS +GLYCEROL +PHOSPHARIC ACID—INOSITOL

SECONDARY MESSENGER FOR OXYTOCIN,VASSOPRESSIN

GLYCEROPHOSPHOLIPIDSTYPE V PHOSPHTIDYL SERINE /PHOSPHOTIDYL THREONINE

• FATTY ACIDS +GLYCEROL +PHOSPHARIC ACID+SERINE

• FATTY ACIDS +GLYCEROL +PHOSPHARIC ACID+ THREONINE

• FOUND IN MOST TISSUES

TYPE VI PLASMALOGENS

• FATTY ACIDS LINKED WITH ETHER LINKAGE (NOT ESTER LINKAGE )

FUNCTIONS

• MYELIN SHEETH FORMATION

• CARDIAC MUSCLES

• PLATELET AGGREGATION

GLYCEROPHOSPHOLIPIDSCARDIOLIPINS

FATTY ACIDS +2 GLYCEROL +2PHOSPHARIC ACID(LINKED THROUGH P GROUP )

ISOLATED FROM HEART MUSCLES

PRESENT IN INNER MITOCHONDRIAL MEMBRANE

ANTIGENIC PROPERTIES

FUNCTIONS OF PHOSPHOLIPIDS1. Along with structural component of membrane regulate membrane permeability

2. ( lecithin /cephalin /cardiolipin )—present in electron transport chain –assist in cell respiration

3. Amphipathic nature – combine with polar & nonpolar compounds

4 .absorption of fat from intestine

5.lipoprotein synthesis---lipid transport (LDL/VLDL/HDL)

6.PREVENT FATTY LIVER—REGARDED AS LIPOTROPIC FACTORS

7.SYNTHESIS OF PROSTAGLANDINS /PROSTCYCLINS /THROMBOXANES

PHOSPHOLIPIDSARACHIDONIC ACIDS-EICOSANOIDS

FUNCTIONS OF PHOSPHOLIPIDS

9. REVERSE CHOLESTEROL TRANSPORT

• Eg LDL carrier of endogenous Cholesterol (LIVER TO PERIFERAL TISSUE)

• VLDL carrier of endogenous TRIGLYCEROL (LIVER TO PERIFERAL TISSUE)

10.SURFACTANT –(LOWERING SURFACE TENSION )—eg –Dipalmitoylphosphatidyl choline –lung surfactant –deficiency respiratory distress syndrome

11.Singnal transmission across the membrane

12.Component of bile –emulsification of fat

Phospholipids—Glycolipids /Sphingolipid

1) fatty acid + glycerol+ nitrogen base + p >>>Glycerophospholipid

2) fatty acid + spingol /sphingosine>>ceramide3) fatty acid + sphingosine+ Nitrogen base > sphingophospholipids

Ceramide

4) fatty acids + sphingosine + carbohydrate *>>>GlycolipidsCeramide + galactose *>>>>

Ceramide+ glucose *>>>>

5) fatty acid + sphingosine + glucose+ ( galactose ---n acetylgalactosamine—galactose )+ NANA ( N ACETYL neuaminicacid ) Ceramide +glucose + galactose ---n acetylgalactosamine—galactose )+NANA

…………. Gangliosides

LIPID STORAGE DISEASE

• LYSOSOMAL STORAGE DEFECT

• INHERITED DISORDERS ( GENETIC DISEASE)

• ACCUMULATION OF COMPLEX LIPIDS-----SPHINGOLIPID/SPHINOMYELINS)

LIPID STORAGE DISEASE

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• GAUCHER”S DISEASE

• GLUCOCERBROSIDES----------------------GLUCOSE + CERAMIDE

• (GLU –CER) BETA GLUCOSIDASE

• SYMPTOMS

• ENLARGEMENT OF LIVER SPLEEN

• OSTEOPOROSIS

• PIGMATION OF SKIN

• ANAEMIA

• MENTAL RETARDATION

• FATAL

LIPID STORAGE DISEASE

• KRABB”S DISEASE

• BETA GALACTOSIDASE

• GALACTOCERBROSIDES--------------------------GALACTOSE + CERAMIDES

• (GAL-CER)

• Absence of myelin in nervous tissue• Mental retardation

• Convulsions

• Blindness• Deafness

• Fatal in early life

•

LIPID STORAGE DISEASE

• Niemann”s Pick”s Disease

• sphingomylinase

• Sphingomylin ----------------------- - choline p+ ceramide

• (choline-p-cer)

• Accumulation of sphingomyelins in liver & spleen-----enlargement

• Mental retardation

• Death early childhood

LIPID STORAGE DISEASE

• Faber”s disease

• Ceramidase

• Ceramide --------------------fatty acid + sphingosine

• Symptoms

• Skeletal deformation

• Subcutaneous nodules

• Dermatitis

• Mental redardation

• Fatal in early life

LIPID STORAGE DISEASE

• GANGLIOSIDES -----COMPLEX GLYCOSPHINGOLIPIDS FOUND IN GANGLIONS.

• THEY CONTAIN ONE OR MORE MOLECULES OF NANA (N acetyl neuraminic acid) BOUND TO CERAMIDE OLIGO SACCHARRIDES.

• DEFECT IN DEGRDTION OF GANGLIOSIDES CAUSES GANGLIOSIDOSIS----

• TAY SACH” S DISEASE

LIPID STORAGE DISEASE

DISEASE DEFECTIVE ENZYME STORAGE COMPOUND SYMPTOMS

NIEMANN”S PICK

SPHINGOMYLINASE SPHINGOMYELINS ENLARGED LIVER & SPLEEN MENTAL RETARDATION

FABERS CERAMIDASE CERAMIDE PAINFUL JOINTS AND DEFORMED JOINTS

GAUCHER”S Β GLUCOSIDASE GLUCOCEREBROSIDE ENLARGED LIVER & SPLEEN MENTAL RETARDATION,OSTEOPOROSIS

LIPID STORAGE DISEASE

DISEASE DEFECTIVE ENZYME STORAGE COMPOUND SYMPTOMS

KRABB”SDISEASE

BETA GALACTOSIDASE

GALACTOCEREBROSIDE ENLARGED LIVER & SPLEEN, ABSENCE OF MYELIN FORMATION MENTAL RETARDATION

TAY SACH”S DISEASE

Hexosaminidase Ganglioside GM2 BLINDNESSPAINFUL JOINTS AND DEFORMED JOINTS

ENLARGED LIVER & SPLEEN MENTAL RETARDATION,DEATH 2-3 YRS

LIPID STORAGE DISEASE

DISEASE DEFECTIVE ENZYME STORAGE COMPOUND SYMPTOMS

FABRY”S ALPHA GALACTOSIDASE

CERAMIDE TRIHEXOSIDE RENAL FAILURE ,SKIN RASH ,PAIN IN LOWEREXTREMITIS

Tay Sach disease: Inheritance

It is inherited as an autosomal recessive traits, with

a predilection in the Ashkenazi Jewish population,

where the carrier frequency is about 1/25.

Diagnosis of Tay-Sach disease

• is usually suspected in an infant with neurologic features and a cherry-red spot.

• Enzymatic Assays-Definitive diagnosis is by determination of the level of ß-hexosaminidase A in isolated blood leukocytes.

• Fine needle Aspiration Cytology of brain tissue – can show the degree of neuronal degeneration. FNAC has a great potential for diagnosis and follow-up of Tay-Sachs disease

• Prenatal screening-Future at-risk pregnancies for both disorders can be monitored by prenatal diagnosis by amniocentesis or chorionic villous sampling.

• Carrier screening- Identification of carriers within families is also possible by ß-hexosaminidase A and B determination.

LIPOSOMES --NANO DRUG DELIVERY SYSTEM

LIPOSOMES • SELECTIVE FUSION OF LIPOSOMES WITH TARGET CELLS –

CONTROLLING DRUG DELIVERY TO SPECIFIC CELLS –CANCER TREATMENT

• REDUCE SIDE EFFECTS OF TOXIC DRUGS

• IMPROVE PHARMOCOKINETIC &PHARMACODYMICS OF DRUGS

DetergentsI NATURAL a. Bile Salts &bile acids Emulsification of fat in GIT

II SYNTHETIC A. Anionic –SODIUM DODECYL SULPHATE (USED IN ELECTROPHORESIS ANALYSIS )PROTEIN +SDS = SOLUBILIZATION OF PROTEINS(SO4 IMPARS NEGATIVE CHARGE ) ---IMPARTS NEGATIVE CHARGEB.CATIONIC ---CETYL TRIMETHYL AMMONIUM BROMIDE (CTAB)ANTIBACTERIAL AGENTS (HAND WASH CREAMS )DESTROYING BACTERIAL MEMBRANE PROTEIN CARRY POSITIVE CHARGE.

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