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Phosphatidylinositol and Phospholipases: Structure, Functions, and Signaling Pathways

Explore the structure and functions of Phosphatidylinositol (PI) in membranes and its role in cell signaling pathways. Learn about various phospholipases involved in phospholipid degradation and remodeling. Discover how PI anchors proteins to membranes and produces second messengers.

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Phosphatidylinositol and Phospholipases: Structure, Functions, and Signaling Pathways

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  1. بسم الله الرحمن الرحيم

  2. Phospatidylinositol and Phospholipases By Reem Sallam, MD, MSc, PhD

  3. Phosphatidylinositol (PI) • Structure • Functions • Plospholipases: • Phospholipases A1, A2, C and D • Lysosomalphospholipase:Sphingomyelinase Objectives

  4. Background: Phospholipids A. Glycerophospholipids Glycerol-containing phospholipids e.g., Phosphatidylinositol B. Sphingo-phospholipids: Sphingosine-containing phospholipids e.g., Sphingolmyelin

  5. Phosphatidylinositol (PI) Diacylglycerol (DAG) Saturated FA Parent Phospholipid Unsaturated FA OH - Inositol Phosphatidylinositol (PI)

  6. Phosphatidylinositol (PI): Functions • Protein anchoring to plasma membranes • Reservoir of arachidonic acid in membranesArachidonic acid is the precursor of prostaglandins • Signal transmission across membranes via production of second messengers:Inositol 1,4,5-trisphosphate (IP3) Diacylglycerol (DAG)

  7. 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

  8. Phosphatidylinositol 4,5 bisphosphate

  9. Calcium/Phosphatidylinositol System Diacylglycerol (DAG) Inositol 1,4,5-Trisphosphate (IP3) Phospholipase C

  10. GTP-Dependant Regulatory Proteins (G-Proteins) Gq-Proteins: Trimeric membrane proteins (αβγ) Binds to GTP/GDP Forms of G-Proteins Active form α-GTP bound (α/GTP) Inactive form Trimeric –GDP bound (αβγ/GDP) The α-subunit has intrinsic GTP-ase activity, resulting in: Hydrolysis of GTP into GDP  Inactivation of G-proteins

  11. Phosphatidylinositol System What is the initial Signal? Hormones or neurotransmitters e.g., Acetylcholine, antidiuretic hormone (V1-receptor) & catecholamines(α1 actions)What is the Receptor? G-protein coupled receptor What are the downstream Effects? Activation of phospholipase C  Hydrolysis of phosphatidylinositol 4,5-bisphosphate Production of : IP3 ( release of Ca2+ from intracellular stores) and DAG Activation of protein kinase C What is the Response? Phosphorylation of cellular proteins response to hormones

  12. Gq * Gq protein with Gq protein * Acetylcholine Antidiuretic hormone (ADH)Catecholamines Intracellular Signaling by Inositol 1,4,5-trisphosphate (IP3)

  13. 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

  14. 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 using fatty acyl CoA transferase • e.g.: • Binding of 2 palmitic acids in Dipalmitoylphosphatidylcholine (DPPC; lung surfactant) • Binding of arachidonic to carbon # 2 of PI or PC

  15. (1) Glycero-phospholipases

  16. Sphingosine-containing phospholipids: Sphingomyelin CH3 (CH2)12 CH CH CH CH CH2O Phosphorylcholine OH NH C (CH2)n CH3 O Long Chain Fatty acid

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

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

  19. Sphingomyelin Sphingomyelin = Ceramide + phosphorylcholine CH3 (CH2)12 CH CH CH CH CH2O Phosphorylcholine OH NH C (CH2)n CH3 O Long Chain Fatty acid

  20. (2) Lysosomal Phospholipase: Sphingomyelinase Degradation of sphingomyelin by sphingomyelinase and ceramidase produce intracellular messengers: Ceramide and sphingosine

  21. Take Home Message • Phosphatidylinositol (PI) is present in membranes • Functions of PI: Anchoring for proteins to membrane Production of second messengers Reservoir of arachidonic acid, a PG precursor • Phospholipases: Phospholipases A1, A2, C andDLysosomal Phospholipase: Sphingomyelinase

  22. Take Home Message CONT’D Function of phospholipases: • Degradation of phospholipids e.g., production of second messengers • Remodeling of phospholipids • e.g., production of DPPC (lung surfactant)

  23. THANK YOU 

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