Download Cell membrane phospholipids

Phospholipids
Phospholipids & Glycolipids
Phospholipids (PL)
PL are composed of an alcohol (ethanolamine, serine, choline,
inositol) attached by a phosphodiester bridge to:
or
Diacylglycerol
Sphingosine
Glycerophospholipids
Sphingolipids
Phospholipids are amphopathic in nature:
Hydrophilic head: phosphate + alcohol (e.g. serine, choline)
Hydrophobic tail: fatty acids
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)
• 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:
Predominant lipids of cell membranes
Anchoring:
Attaching some proteins to membranes
Signaling:
Source of PI3 & DAG
Myelin sheath: insulator & speeds up transmission of nerve
impulse
Non-membrane-bound phospholipids
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: Platelet-activating factor (PAF)
Structural: Coat of lipoproteins
Structural Classification of Phospholipids
1- Glycerolphospholipids:
with glycerol backbone
2- Sphingolipids (sphingomyelin):
with sphingosine backbone
Important glycerophospholipids
1- Phosphatidylcholine (Lecithin)
2- Phosphatidylinositol (PI)
2- Platelet-activating factor (PAF)
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)
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
Role of PI in signal transduction
PI bound to membranes is phosphorylated
to Phosphatidylinositol 4,5 bisphosphate (PIP2)
PIP2 is 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
Role of PI in signal transduction
Phosphatidyl choline (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
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)
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)
RDS may occur in adults
when surfactant-producing pnemocytes are damaged or destroyed
(e.g. by infection, trauma or immunosuppressive medication or
chemotheraputic drugs)
Platelet-activating factor (PAF)
1. Mediates:
1. Acute inflammatory reactions
2. Hypersensitivity reactions
2. Stimulates:
1. Platelet aggregation
2. Neutrophils & alveolar macrophages to
generate superoxide radicals as an
antibacterial defense mechanism
Cardiolpin
•
important component of
inner mitochondrial membrane
•
Antigenic importance:
It is recognized by antibodies
against Trponema pallidum
bactria (bacteria causing syphilis)
(diphosphaidylglycerol)
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
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
Phospholipase activity is also available in:
1- toxins & venoms
2- several pathogenic bacteria
produce phosphlipases that dissolve cell membranes & allow the
spread of infection
Degradation of Sphingomyelin
Sphingomyelin
sphingomyelinase
P-Choline
(a lysosomal enzyme)
Ceramide
ceramidase
sphingosine
+
FA
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