Phospholipids

Phospholipids & Glycolipids

Phospholipids (PL) alcohol phosphodiester bridge PL are composed of an alcohol (ethanolamine, serine, choline, inositol) attached by a phosphodiester bridge to: Diacylglycerol Glycerophospholipids or Sphingosine Sphingolipids amphopathic Phospholipids are amphopathic in nature: Hydrophilic head Hydrophilic head: phosphate + alcohol (e.g. serine, choline) Hydrophobic tail Hydrophobic tail: fatty acids

Cell membrane phospholipids (Membrane-bound)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)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) Locations 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 phospholipids Structural Anchoring Signaling Structural: Predominant lipids of cell membranes Anchoring: Attaching some proteins to membranes Signaling: Source of PI3 & DAG Myelin sheath: Myelin sheath: insulator & speeds up transmission of nerve impulse

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

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

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

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

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

Role of PI in signal transduction PI bound to membranes is phosphorylated to Phosphatidylinositol 4,5 bisphosphate (PIP 2 ) phospholipase C PIP 2 is degraded by phospholipase C to: IP3DAG Inositol 1,4,5- triphosphate (IP3) & diacylglycerol (DAG) 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 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)

Role of phosphatidylcholine (PC) in 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) preterm infants occurs i n preterm infants insufficient surfactant production and/or secretion associated with insufficient surfactant production and/or secretion neonatal death is a significant cause of neonatal death Ratio of DPPC/sphingomyelin (L/S) in amniotic fluidRatio 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 pneumocytes at about 32 weeks of gestation Synthesis occurs in pneumocytes 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.Mediates: inflammatory 1.Acute inflammatory reactions 2.Hypersensitivity 2.Hypersensitivity reactions 2.Stimulates: 1.Platelet 1.Platelet aggregation 2.Neutrophils & alveolar macrophages to generate superoxide radicals as an antibacterial defense mechanism 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 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

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

Degradation of phosphoglycerides

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 sphingomyelinase P-Choline sphingomyelinase (a lysosomal enzyme) Ceramide ceramidase sphingosine + FA Degradation of Sphingomyelin

Niemann-Pick disease (type A & B) Autosomal recessiveAutosomal recessive sphingomyelinaseDeficiency in sphingomyelinase resulting in inability to degrade sphingomyelin Type A: severe infantile (rare) lipid is deposited in liver and spleen enlarged neurodegeneration 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