Phospholipids

Phospholipids & GlycolipidsPhospholipids & Glycolipids

Phospholipids (PL) PL are composed of an alcoholalcohol (ethanolamine, serine, choline, inositol) attached by a phosphodiester bridge phosphodiester bridge to:

Diacylglycerol Glycerophospholipidsor Sphingosine Sphingolipids

Phospholipids are amphopathic amphopathic in nature:

Hydrophilic headHydrophilic head: phosphate + alcohol (e.g. serine, choline)Hydrophobic tailHydrophobic tail: fatty acids

• Cell membrane phospholipidsCell membrane phospholipids (Membrane-bound)(Membrane-bound)

Phosopholipids are the predominant lipids of cell membranePhosopholipids are the predominant lipids of cell membrane

Hydrophobic portion of PL: Hydrophobic portion of PL: is associated with the nonpolar portion of the membrane constituents(glycolipids, proteins & cholesterol)

Hydrophilic head of PL (polar):Hydrophilic head of PL (polar):Extends outward facing intracellular or extracellular aqueous environment

• Non-membrane phospholipids Non-membrane phospholipids (Non-membrane bound)(Non-membrane bound)

with certain functions in the body:with certain functions in the body: e.g. Components of lung surfactant Essential components of bile (solubilization of cholesterol)

Locations of PhospholipidsLocations of Phospholipids

• Phospholipids (PLs) are the predominant lipids of the cell membranes

• The hydrophilic heads of PLs protrude outwards facing the extracellular & intracellular aqueous medium

Membrane-bound phospholipidsMembrane-bound phospholipids

StructuralStructural: Predominant lipids of cell membranes

AnchoringAnchoring: Attaching some proteins to membranes

SignalingSignaling: Source of PI3 & DAG

Myelin sheathMyelin sheath: : insulator & speeds up transmission of nerve impulse

Easy re-inflation of alveoli by airEasy re-inflation of alveoli by air: lung surfactant

PLs are essential components of bilePLs are essential components of bile -- solubilize cholesterolsolubilize cholesterol - preventing gall stones- preventing gall stones

- emulsifying lipids for helping lipid digestion - emulsifying lipids for helping lipid digestion

Bioactive moleculeBioactive molecule: Platelet-activating factor (PAF)

Structural:Structural: Coat of lipoproteins

Non-membrane-bound phospholipidsNon-membrane-bound phospholipids

Structural Classification of PhospholipidsStructural Classification of Phospholipids

1- GlycerolphospholipidsGlycerolphospholipids: with glycerol backbone

2- Sphingolipids (sphingomyelin)Sphingolipids (sphingomyelin): with sphingosine backbone

1- Phosphatidylcholine (Lecithin)

2- Phosphatidylinositol (PI)

2- Platelet-activating factor (PAF)

Important glycerophospholipidsImportant glycerophospholipids

Phosphatidylinositol (PI)Phosphatidylinositol (PI)

1- Protein anchoring to plasma membranesProtein anchoring to plasma membranes

2. Reservoir of arachidonic acid in membranes:Reservoir of arachidonic acid in membranes: arachidonic acid is the precursor of prostaglandins

3. Signal transmission across membranes via production Signal transmission across membranes via production of second messengers: of second messengers:

inositol 1,4,5-trisphosphate (IP3) & diacylglycerol (DAG)

Phosphatidylinositol - Protein AnchorinPhosphatidylinositol - Protein Anchoringg

Anchoring of proteins to membranes via

carbohydrate-phosphatidylinositol bridge

Examples of anchored proteins:

1- Alkaline phosphatase Alkaline phosphatase

(to the surface of small intestine)

2- Acetylcholine esterase Acetylcholine esterase

(to postsynaptic membrane)

These proteins can be cleaved from their

attachment to the membranes

by phospholipase C

Role of PI in signal transductionRole of PI in signal transduction

PI bound to membranes is phosphorylated to Phosphatidylinositol 4,5 bisphosphate (PIP2)

PIP2 is degraded by phospholipase Cphospholipase C to:

Inositol 1,4,5- triphosphate (IP3IP3) & diacylglycerol (DAGDAG)

Phospholipase C is activated by protein G (subunit)as a result of binding of hormone to its receptor on the cell membrane

Role of PI in signal transductionRole of PI in signal transduction

PC is important in the liver:• The liver exports significant amounts of PC in the bile• PC is a component of lipoproteins in blood

Phosphatidyl choline (PC)Phosphatidyl choline (PC)

Role of phosphatidylcholine (PC) Role of phosphatidylcholine (PC) in lung surfactantin lung surfactant

• Dipalmitoylphosphatidylcholine (DPPC) or Dipalmitoyllecithin

• DPPC is synthesized by pneumocytes

• DPPC is the major lipid component of lung surfactant (extracellular fluid layer lining the alveoli) Surfactant reduces the pressure needed to reinflate alveoli So, it prevents alveolar collapse (atelectasis)

Respiratory Distress Syndrome (RDS)Respiratory Distress Syndrome (RDS)

occurs in preterm infantspreterm infants associated with insufficient surfactant production and/or secretioninsufficient surfactant production and/or secretion is a significant cause of neonatal deathneonatal death

• Ratio of Ratio of DPPC/sphingomyelin (L/S)DPPC/sphingomyelin (L/S) in amniotic fluid in amniotic fluid

used to estimate lung maturity of newborn a ratio of 2 or more is evident of maturity of lung as it reflects major shift from sphingomyelin to DPPC Synthesis occurs in pnemcytes at about 32 weeks of gestationpnemcytes at about 32 weeks of gestation

• Lung maturation can be accelerated by giving glucocorticoids to mothers shortly before delivery

• RDS in treated or prevented in newborns by intratracheal instillation of surfactant (natural or synthetic)

RDS may occur in adults when surfactant-producing pnemocytes are damaged or destroyed

(e.g. by infection, trauma or immunosuppressive medication or

chemotheraputic drugs)

1.1. MediatesMediates: : 1. Acute inflammatoryinflammatory reactions

2.2. HypersensitivityHypersensitivity reactions

2.2. StimulatesStimulates: : 1.1. PlateletPlatelet aggregation

2. Neutrophils & alveolar macrophages to generate superoxide radicals as an antibacterial defense mechanism

Platelet-activating factor (PAF)Platelet-activating factor (PAF)

Cardiolpin (diphosphaidylglycerol)

• important component of inner mitochondrial membrane • Antigenic importance: It is recognized by antibodies against Trponema pallidum bactria (bacteria causing syphilis)

Sphingomyelin is a major lipid Sphingomyelin is a major lipid in nerve tissue membranesin nerve tissue membranes

1-Sphingomyelin of the myelin sheath contains predominantly longer-chain fatty acids such as lgnoceric & nervonic acid Myelin sheath is a layered membranous structure that insulates & protects neuronal fibres of CNS

2-Sphingomyelin of the grey matter of the brain contains primarily stearic acid

Myelin SheathMyelin Sheath

Myelin sheath insulates the nerve axon to avoid signal Myelin sheath insulates the nerve axon to avoid signal leakage and greatly speeds up the transmission of leakage and greatly speeds up the transmission of

impulses along axonsimpulses along axons

Direction of nerve impulse

Degradation of phosphoglyceridesDegradation of phosphoglycerides

Functions of Phospholipases1- Degradation of phospholipidsDegradation of phospholipids Production of second messengers Digestion of phospholipids by pancreatic juice Pathogenic bacteria degrade phospholipids of membranes spread of infection

2- Remodeling of phospholipids:Remodeling of phospholipids: Specific phospholipase removes fatty acid from phospholipid. Replacement of fatty acid by alternative fatty acid e.g.:

Binding of 2 palmitic acids in dipalmitoylphosphatidylcholine (DPPC; lung surfactant) Binding of arachidonic to carbon # 2 of PI or PC

Phospholipase activity is also available in:

1- toxins & venoms

2- several pathogenic bacteria produce phosphlipases that dissolve cell membranes & allow the

spread of infection

Sphingomyelin

P-Choline sphingomyelinase sphingomyelinase (a lysosomal enzyme)

Ceramide ceramidase

sphingosine + FA

Degradation of SphingomyelinDegradation of Sphingomyelin

Niemann-Pick disease (type A & B)

• Autosomal recessive• Deficiency in sphingomyelinase resulting in inability to degrade sphingomyelin

• Type A: severe infantile (rare) lipid is deposited in liver and spleen enlarged Progressive neurodegeneration due to deposition of sphingomyelin in CNS Death in early childhood

• Type B: less severe no damage (or little) damage to neural tissue but, spleen, liver & lung & bone marrow are affected Death in early adulthood