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Phospholipids

Phospholipids. Phospholipids & Glycolipids. Phospholipids (PL). PL are composed of an alcohol (ethanolamine, serine, choline , inositol ) attached by a phosphodiester bridge to: Diacyl glycerol Glycerophospholipids or Sphingosine Sphingolipids

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Phospholipids

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  1. Phospholipids

  2. Phospholipids & Glycolipids

  3. Phospholipids (PL) PL are composed of an alcohol(ethanolamine, serine, choline, inositol) attached by a phosphodiester bridge to: DiacylglycerolGlycerophospholipids or SphingosineSphingolipids Phospholipids are amphopathicin nature: Hydrophilic head: phosphate + alcohol (e.g. serine, choline) Hydrophobic tail: fatty acids

  4. Locations of Phospholipids • Cell membrane phospholipids(Membrane-bound) Phosopholipids are the predominant lipids of cell membrane Hydrophobic portion of PL: is associated with the nonpolar portion of the membrane constituents (glycolipids, proteins & cholesterol) Hydrophilic head of PL (polar): Extends outward facing intracellular or extracellular aqueous environment • Non-membrane phospholipids (Non-membrane bound) with certain functions in the body: e.g. Components of lung surfactant Essential components of bile (solubilization of cholesterol)

  5. Phospholipids (PLs) are the predominant lipids of the cell membranes • The hydrophilic heads of PLs protrude outwards facing the extracellular & intracellular aqueous medium

  6. Membrane-bound phospholipids Structural: Predominant lipids of cell membranesAnchoring: Attaching some proteins to membranesSignaling: Source of PI3 & DAG Myelin sheath: insulator & speeds up transmission of nerve impulse

  7. Non-membrane-bound phospholipids Easy re-inflation of alveoli by air: lung surfactantPLs are essential components of bile -solubilize cholesterol - preventing gall stones - emulsifying lipids for helping lipid digestion Bioactive molecule: Platelet-activating factor (PAF) Structural: Coat of lipoproteins

  8. Structural Classification of Phospholipids 1- Glycerolphospholipids: with glycerol backbone 2-Sphingolipids (sphingomyelin): with sphingosinebackbone

  9. Important glycerophospholipids 1- Phosphatidylcholine (Lecithin) 2- Phosphatidylinositol (PI) 2- Platelet-activating factor (PAF)

  10. Phosphatidylinositol (PI) • 1- Protein anchoring to plasma membranes • 2. Reservoir of arachidonic acid in membranes: • arachidonic acid is the precursor of prostaglandins • 3. Signal transmission across membranes via production of second messengers: • inositol 1,4,5-trisphosphate (IP3) & diacylglycerol (DAG)

  11. Phosphatidylinositol - Protein Anchoring Anchoring of proteins to membranes via carbohydrate-phosphatidylinositol bridge Examples of anchored proteins: 1- Alkaline phosphatase (to the surface of small intestine) 2- Acetylcholine esterase (to postsynaptic membrane) These proteins can be cleaved from their attachment to the membranes by phospholipase C

  12. Role of PI in signal transduction PIbound to membranes is phosphorylated to Phosphatidylinositol 4,5 bisphosphate (PIP2) PIP2is degraded by phospholipase C to: Inositol 1,4,5- triphosphate (IP3) & diacylglycerol (DAG) Phospholipase C is activated by protein G (a subunit) as a result of binding of hormone to its receptor on the cell membrane

  13. Role of PI in signal transduction

  14. Phosphatidylcholine (PC) PC is important in the liver: • The liver exports significant amounts of PC in the bile • PC is a component of lipoproteins in blood

  15. Role of phosphatidylcholine (PC) in lung surfactant • Dipalmitoylphosphatidylcholine (DPPC) or Dipalmitoyllecithin • DPPCis synthesized by pneumocytes • DPPCis 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)

  16. Respiratory Distress Syndrome (RDS) occurs in preterm infants associated with insufficient surfactant production and/or secretion is a significant cause of neonatal death • Ratio of DPPC/sphingomyelin (L/S) 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 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)

  17. RDS may occur in adults when surfactant-producing pnemocytes are damaged or destroyed (e.g. by infection, trauma or immunosuppressive medication or chemotheraputic drugs)

  18. Platelet-activating factor (PAF) • Mediates: • Acute inflammatory reactions • Hypersensitivity reactions • Stimulates: • Platelet aggregation • Neutrophils & alveolar macrophages to generate superoxide radicals as an antibacterial defense mechanism

  19. Cardiolpin(diphosphaidylglycerol) • important component of inner mitochondrial membrane • Antigenic importance: It is recognized by antibodies against Trponemapallidum bactria (bacteria causing syphilis)

  20. Sphingomyelin is a major lipid in 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

  21. Myelin Sheath Myelin sheath insulates the nerve axon to avoid signal leakage and greatly speeds up the transmission of impulses along axons Direction of nerve impulse

  22. Degradation of phosphoglycerides

  23. Functions of Phospholipases • 1- Degradation 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: • 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

  24. Phospholipase activity is also available in: 1- toxins & venoms 2- several pathogenic bacteria produce phosphlipases that dissolve cell membranes & allow the spread of infection

  25. Degradation of Sphingomyelin Sphingomyelin P-Cholinesphingomyelinase (a lysosomal enzyme) Ceramide ceramidase sphingosine + FA

  26. 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

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