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Overview of Physiological Importance and Functions of Phospholipid Compounds

This article presents an in-depth exploration of phospholipids, highlighting their vital roles in biological systems. It covers various types of phospholipids, including glycerophospholipids and sphingomyelin, and their critical functions such as membrane structure, signaling, and surfactant properties essential for lung health. The therapeutic relevance of phospholipids in conditions like congenital respiratory distress syndrome (RDS) is discussed, along with mechanisms involving phospholipases and cellular signaling pathways. Understanding these components is crucial for appreciating their physiological significance.

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Overview of Physiological Importance and Functions of Phospholipid Compounds

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  1. بسم الله الرحمن الرحيم

  2. Phospholipid Compounds of Physiological Importance By Reem M. Sallam, M.D.; Ph.D.

  3. Objectives • To introduce selected members of phospholipids • To understand the physiological importance of phospholipids • To recognize the roles of specific plospholipases: • PhospholipasesA1, A2, C andD • Lysosomalphospholipase:Sphingomyelinase

  4. Background: Lipid Compounds • Heterogeneous group • Relatively water-insoluble (with the exception of Ketone bodies) • Soluble in non-polar solvents

  5. Lipid Compounds: Heterogeneous Group • Simple Lipids: • Fatty acids • Ketonebodies • Triacylglycerol • Cholesterol • Complex Lipids: • Phospholipids • Lipoproteins • Glycolipids

  6. Functions of Phospholipids • Membrane-bound phospholipids:Structural: They are the predominant lipids of cell membranesAnchoring: Attaching some proteins to membranesSignaling: Acting as a source of PI3 and DAG Example of specific functions: Myelin sheath is an insulator and speeds up transmission of nerve impulses

  7. Functions of Phospholipids CONT’D • Non-membrane-bound phospholipids: • Easy re-inflation of alveoli by air: Lung surfactant • Detergent effect: Phospholipids are essential component of bile: Solubilize cholesterol and preventing gall stones Emulsifying lipids and helping their digestion • Structural: Coat of lipoproteins

  8. Phospholipids Glycerophospholipids Glycerol-containing phospholipids Sphingo-phospholipids: Sphingosine-containing phospholipids

  9. Phospholipids A. Glycerophospholipids: Phosphatidylcholine(Lecithin) e.g., Surfactant (Dipalmitoylecithin) Phosphatidylinositol(Signaling and anchoring molecule)

  10. Phospholipids: A. Glycerophospholipids Members: Phosphatidylcholine (Lecithin) e.g., Surfactant (Dipalmitoylecithin) Parent Compound Phosphatidic acid

  11. Phospholipids: Glycerophospholipids DipalmitoylLecithin (Lung surfactant) • Synthesis and secretion: by granular pneumocytes • Major lipid component of lung surfactant • Lung surfactant is made out of: • Dipalmitolylecithin (65%) • Other phospholipids, cholesterol & proteins (35%)

  12. Phospholipids: Glycerophospholipids DipalmitoylLecithin (Lung surfactant), continued… Surfactantdecreases surface tension of fluid layer lining of alveoli↓the pressure needed for their inflation by air preventing alveolar collapse (atelectasis) Congenital Respiratory distress syndrome (RDS): Insufficient production of lung surfactant (especially in pre-term babies)  neonatal death

  13. Congenital RDS Diagnosis • Pre-natal diagnosis by: • Lecithin/sphingomyelin (L/S) ratio in amniotic fluid: • Ratio of 2 or above indicates lung maturity and no RDS (i.e., shift from sphingomyelin to lecithin synthesis by pneumocytesthat normally occurs by 32 weeks of gestation) • Low L/S Ratio (< 2): RDS

  14. Congenital RDS Prevention & Treatment • Prevention of RDS: • Glucocorticoids to the pregnant mother with low L/S ratio shortly before delivery • Treatment: • Intratrachealadministration of surfactant to pre-term infants with RDS

  15. Phospholipids: Glycerophospholipids Phosphatidylinositol 4,5 bisphosphate

  16. Calcium/Phosphatidylinositol System Diacylglycerol (DAG) Inositol Trisphosphate (IP3) Phospholipase C

  17. Phosphatidylinositol System Signal: Hormones or neurotransmitters e.g., Acetylcholine, antidiuretic hormone (V1- receptor) and catecholamines(α1 actions) Receptor: G-protein coupled receptor Effects: Activation of phospholipase C Hydrolysis of phosphatidylinositol4,5-bisphosphateIP3 ( Ca2+) + DAG Activation of protein kinase C Response: Phosphorylation of cellular proteins and responses to hormones

  18. * * Acetylcholine Antidiuretic hormone (ADH)Catecholamines Intracellular Signaling by Inositol trisphosphate

  19. PI- 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 • byphospholipase C

  20. Phospholipids B. Sphingo-phospholipids: Sphingosine-containing phospholipids: e.g., sphingomyelin (Myelin sheath)

  21. Phospholipids: B. Sphingo-phospholipids Sphingomyelin CH3 (CH2)12 CH CH CH CH CH2O Phosphorylcholine OH NH C (CH2)n CH3 O Long Chain Fatty acid

  22. Sphingosine CH3 (CH2)12 CH CH CH CH CH2OH OH NH2 Long chain, unsaturated amino alcohol

  23. Ceramide: Parent Sphingolipid Compound CH3 (CH2)12 CH CH CH CH CH2OH OH NH C (CH2)n CH3 O Long Chain Fatty acid

  24. Sphingomyelin CH3 (CH2)12 CH CH CH CH CH2O Phosphorylcholine OH NH C (CH2)n CH3 O Long Chain Fatty acid

  25. Structure & Function of Myelin Sheath Glycolipids (mainly) Myelin structure: Lipids (80%) Sphingomyelin Proteins (20%) Myelin sheath insulates the nerve axon to avoid signal leakage and greatly speeds up the transmission of impulses along axons Direction of nerve impulse

  26. Lipoprotein Structure • Outer part (coat): • Apoproteins or apolipoproteins • Phospholipids(amphipathic) • Free cholesterol • (Relatively hydrophilic, allowing transport of lipid particles of the core in the aqueous plasma) • Inner part (core): • According to the type of lipoproteins • Different lipid components in various combinations

  27. Lipoprotein Structure

  28. Phospholipases • (1) For glycerophospholipids: • PhospholipasesA1, A2, C andD • Present in all tissues and pancreatic juice • Present in snake venoms and bacterial toxins • (2) For sphingophospholipids: • Lysosomalphospholipase • Sphingomyelinase • SphingomyelinCeramide + Phosphocholine

  29. Glycero-phospholipases

  30. Functions of Phospholipases • (1) Degradation of phospholipids • Production of second messengers • Digestion of phospholipids by pancreatic juice • Pathogenic bacteria degrade phospholipids of membranes and causing spread of infection • (2) Remodeling of phospholipids: • Specific phospholipase removes fatty acid from phospholipid • Replacement of fatty acid by alternative fatty acid using fatty acylCoAtransferase • e.g., Binding of 2 palmitic acids in: Dipalmitoylphosphatidylcholine(DPPC) • Binding of arachidonic to carbon 2 of PI or PC

  31. Take Home Message • Phospholipidsare Complex lipids • Phospholipidshave important physiological functions: A. Membrane-bound: StructuralSignalling& anchoring: e.g., PI Myelin sheath: e.g., sphingomyelin B. Non-membrane bound: Structural: Lipoprotein coatAlveolar re-inflation: Lung surfactantDetergent effect: Phospholipids of bile

  32. Take Home Message CONT’D Phospholipases:PhospholipasesA1, A2, C andDLysosomalPhospholipase: Sphingomyelinase Function of phospholipases: • Degradation of phospholipids e.g., production of second messengers • Remodeling of phospholipids • e.g., production of DPPC (lung surfactant)

  33. THANK YOU

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