PHOSPHO LIPIDS

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PHOSPHO LIPIDS

• M.Prasad Naidu
• MSc Medical Biochemistry, Ph.D,.

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Definition

• Phospholipids are polar , ionic compounds
  composed of an alcohol that is attached by a
  phosphodiester bridge to either diacylglycerol
  or to sphingosine

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Introduction

• Phospholipids are amphipathic in nature they have
  hydrophilic head ( the phosphate group what
  ever attached to itserine,ethanolamine,choline
  ,etc) a long hydrophobic tail ( containing 2
  fatty acid chains ).
• Phospholipids are the major lipids of the cell
  membranes.

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phospholipids

• There are 2 classes of phospholipids
• 1 ) those that have glycerol as back
  bone (phosphoglycerides )
• 2 ) those that contain sphingosine
  (sphingomyelins ) .

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Phosphoglycerides

• Phosphoglycerides constitutes the major class of
  phospholipids .
• Phosphatidic acid is the simplest
  phosphoglyceride is the precursor of the other
  phophoglycerides triacylglycerol synthesis .
• Phospholipids are formed from phosphatidic acid
  an alcohol .

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• PHOSPHOLIPIDS are synthesized in the smooth
  endoplasmic reticulum.
• From there they are transported to the golgi
  apparatus then to membranes of organelles or
  the plasma membrane or are secreted by the cell
  by exocytosis.

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Phosphatidyl Ethanolamine ( Cephalin )
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Uses of Cephalin

• Cephalin is found in all living cells, although
  in human physiology it is found particularly in
  nervous tissue such as the white matter of brain,
  nerves, neural tissue, and in spinal cord.
  Whereas lecithin is the principal phospholipid in
  animals, cephalin is the principal one in
  bacteria.
• As a polar head group phosphatidylethanolamine
  creates a more fluid lipid membrane compared to
  phosphatidylcholine

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Phosphatidyl choline

• Phosphatidyl choilne is also called as lecithin .
• Dipalmityl phosphotidyl choline is lung
  surfactant .
• Choline is reutilized in the body .
• Phosphatidylcholine is a major constituent of
  cell membranes, and also plays a role in
  membrane-mediated cell signalling.

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Phosphatidyl Serine Structure
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Phosphotidyl Inositiol

• PI is synthesized from the free myoinosiotol
  CDP- Diacyl glycerol .
• PI is an unusual phospholipid it contains Stearic
  acid in C-1 position arachidonic acid on C- 2
  of glycerol .
• PI has role in signal transmission across
  membrane .
• PI has role in membrane protein anchoring.

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Phosphatidyl Inositol
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• 1.Role of PI in signal transmission across
  membranes
• phosphorylation of PI occur in response to
  binding of neurotransmitter,hormones
  ,growthfactors to receptors on cell membrane.
• The degradation of this PI result in mobilization
  of intra cellular calcium activation of protein
  kinase c.
• Both act synergistically promote cellular
  responses,resulting in signal transmission across
  the membrane.

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• 2.Role of PI in membrane protein anchoring
• Specific proteins are covalently attached by a
  carbohydrate bridge to membrane bound PI.
• egalkaline phosphatasedigestive enzyme
• attacks organic phosphates.
• acetyl choline esterasedegrades
  neuro-
• transmitter acetylcholine.
• Some proteins are found in parasitic protozoans

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• Egtoxoplasma,leishmania etc.
• These proteins allow PI glycan anchored protein
  rapid mobility on surface of plasma membrane.
• These proteins can be cleaved from anchor by
  phospholipase-C releasing DAG that activate
  protein kinase-c.

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Cardiolipin

• Cardiolipin is formed when two molecules of
  phosphatidic acid esterified through their
  phosphate groups to an additional molecule of
  glycerol .
• This is the only human phospholipid that is
  antigenic .
• Cardiolipin is an important component of the
  inner mitochondrial membrane .

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Phosphotidyl Glycerol
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Cardiolipin Structure
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Uses

• Because of cardiolipins unique bicyclic
  structure, a change in pH and the presence of
  divalent cations can induce a structural change.
  CL shows a great variety of forms of aggregates.
  It is found that in the presence of Ca2 or other
  divalent cations, CL can be induced to have a
  lamellar-to-hexagonal phase transition. And it is
  believed to have a close connection with membrane
  fusion.

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• Helps to build quaternary structure
• The enzyme cytochrome c oxidase or Complex IV is
  a large transmembrane protein complex found in
  bacteria and the mitochondrion.
• It is the last enzyme in the respiratory electron
  transport chain of mitochondria (or bacteria)
  located in the mitochondrial (or bacterial)
  membrane.
• It receives an electron from each of four
  cytochrome c molecules, and transfers them to one
  oxygen molecule, converting molecular oxygen to
  two molecules of water.
• Complex IV has been shown to require two
  associated CL molecules in order to maintain its
  full enzymatic function. Cytochrome bc1(Complex
  III) also needs cardiolipin to maintain its
  quaternary structure and to maintains its
  functional role.
• Complex V of the oxidative phosphorylation
  machinery also displays high binding affinity for
  CL, binding four molecules of CL per molecule of
  complex V.

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• Triggers apoptosis
• During apoptosis, cytochrome c (cyt c) is
  released from the intermembrane spaces of
  mitochondria into the cytosol.
• Cyt c can then bind to the IP3 receptor on ER,
  stimulating calcium release, which then reacts
  back to cause the release of cytochrome c. When
  the calcium concentration reaches a toxic level,
  this causes cell death. Cytochrome c is thought
  to play a role in apoptosis via the release of
  apoptotic factors from the mitochondria .
• A cardiolipin-specific oxygenase produces CL
  hydroperoxides which can result the conformation
  change of the lipid. Then, the oxidized CL first
  transfers from inner membrane to the outer
  membrane and then helps to form a permeable pore
  which releases cyt c.

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• Serves as proton trap for oxidative
  phosphorylation
• During the oxidative phosphorylation process
  catalyzed by Complex IV, large quantities of
  protons are transfered from one side of the
  membrane to another side causing a large pH
  change.
• CL is suggested to function as a proton trap
  within the mitochondrial membranes, thereby
  strictly localizing the proton pool and
  minimizing the changes in pH in the mitochondrial
  intermembrane space.
• This function is due to CLs unique structure. As
  stated above, CL can trap a proton within the
  bicyclic structure while carrying a negative
  charge. Thus, this bicyclic structure can serve
  as an electron buffer pool to release or absorb
  protons to maintain the pH near the membranes.

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Plasmalogens

• When unsaturated fatty acid attached by an ether
  rather than by ester linkage at carbon 1 of the
  core glycerol molecule a plasmalogen is produced
  .
• 1 alkenyl, 2 acetyl phosphatidal choline is
  platelet activating factor , this is a
  plasmalogen .

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• Effects of PAF include
• Increasing airway pulmonary edema in lungs.
• It serve as mediator of hypersensitivity,acute
  inflammatory reactions anaphylactic shock,
• causing neutrophils,alveolar macrophages
  to generate superoxide radicals.
• PAF causes these responses by binding to receptor
  on cell membrane activating transmembrane
  signaling mechanisms.

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uses

• In many tissues plasmalogens are minor
  constituents, but in heart tissue nearly 50 of
  phosphatidylcholine contains the alkenyl ether at
  carbon 1.
• Nervous tissues, contains large amounts of
  ethynolamine plasmalogen .
• Testes and kidneys also contain significant
  amounts of plasmalogens.
• Alkenyl ether-containing phospholipids can
  protect cells against the damaging effects of
  singlet oxygen, which at high concentrations can
  kill cells.

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Sphingomyelin

• The back bone of sphingomyelin is the amino
  alcohol sphingosine rather than glycerol .
• A fatty acid is attached to the amino group of
  sphingosine by an amide linkage , producing
  ceramide this is present in all sphingolipids.
• The fatty acids found most frequently in
  sphingomyelin are palmitic , stearic , lignoceric
  , nervonic acids .
• The alcohol group at carbon 1 of sphingosine is
  esterified to phosphoryl choline producing
  sphingomyelin , an important constituent of the
  myelin of nerve fibers .

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Sphingomyelin
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USES

• Sphingomyelin of the myelin sheath ( a structure
  that insulates protects neuronal fibers of
  C.N.S ) contains predominantly longer chain fatty
  acids such lignoceric nervonic acid .
• Grey matter of brain has sphingomyelin that
  contains primarily stearic acid.

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Phosphilipids role in Membranes

• The favoured structure for most phospholipids in
  aqueous media is bimolecular sheet rather han a
  micelle .
• The reason for this is two fatty acyl chains of a
  phospholipid are too bulky to fit into the
  interior of the micelle .
• Formation of bilayers instead of micelles is of
  critical biological importance .

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contd

• Formation of bilayers is a self assembly process
  .
• Hydrostatic forces are the major driving forces
  for the formation of lipid bilayers.
• Water molecules are released from the hydrocarbon
  tails as these tails become sequestered in the
  non polar interior of the membrane .
• Vanderwalls forces between hydrocarbon tails
  favours close packing of tails .

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contd

• There are electrostatic hydrogen bonding
  attractions between polar head groups water
  molecules .
• Liposomes are aqueous compartments enclosed by a
  lipid bilayer .
• Liposomes are useful for delivery of drugs
  enzymes to the targeted organs .

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Functions of Phospholipids

• Phospholipids play a role in blood coagulation (
  activation of clotting factors prothrombin
  factor 8 requires PL ).
• Role in lipid absorption lecithin lowers
  surface tension of water aids in emulsification
  of lipid water mixtures .
• Role in transport of lipids from intestine
  exogenous TAG is carried as lipoprotein complex ,
  chylomicrons in which PL takes an active part.

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contd

• PL exist as component of VLDL particle helps in
  transport of lipids from liver .
• As most important storage of choline helps in
  lipotropic action of choline .
• L/S ratio in amniotic fluid prior to 34 weeks of
  gestation is useful in assesing fetal lung
  maturity .
• L/S ratio more than 2 5 indicates adequate lung
  maturity .
• L/S ratio less than 1 indicates lung immaturity.

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• Degradation of phospholipids
• By phospholipases found in all tissues
  pancreatic juice.
• Toxins venoms have phospholipase activity.
• Pathogenic bacteria produce phospholipases that
  dissolve cell membrane spread infection.
• A.Degradation of phosphoglycerides
• They hydrolyse esters of phosphodiester bonds at
  specific site.

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• Normal plasma levels of phospholipids
• 125-275mg / dL
• METHOD OF MEASUREMENT
• THIN LAYER CHROMATOGRAPHY
• METHODS TO MEASURE PULMONARY SURFACTANT
• LECITHIN/SPHINGOMYELIN (L/S) RATIO
• DPPC MEASUREMENT BY TLC
• PHOSPHATIDYLGLYCEROL
• FOAM STABILITY INDEX
• FLUORESCENCE POLARIZATION
• LAMELLAR BODY COUNTS

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