Polar Lipid Synthesis

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Polar Lipid Synthesis
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Lipids Role in Signaling
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Signal amplification
1st messenger (hormone, neurotransmitter, growth
factor, etc.)
Modulator ( G protein, receptor tyrosine kinase)
Enzyme activation (phospholipases, adenylate
cyclase)
2nd messenger (calcium, cAMP, IP3, DAG, ceramide)
Enzyme activation (PKA, PKC, phosphatases)
substrates
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Discovery of the "phospholipid effect" by Hokin
MR et al. phosphorus incorporation into
phospholipids showed a remarkable increase in
pigeon pancreas slices on stimulation with
acetylcholine (J Biol Chem 1953, 203, 967).
Michell RH in a famous review proposed for the
first time that the "phosphoinositide effect
discovered in 1953 by Hokin plays a role in
cellular calcium mobilization (Biochim Biophys
Acta 1975, 415, 81) Univ. of Birmingham, UK
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Rates of lipid flip-flop across
bilayers Diacylgycerol 0.1 sec Ceramide 10
min Phosphatdiylcholine 10 hr Lysophosphatidic
acid gt10 hr Ganglioside gtgt10 hr Conclusion
as the headgroup becomes more polar or larger
and as the hydrophobic moiety becomes
smaller, the lipid flips less readily
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ceramide
Ceramide-activated protein phosphatase (PP2A, PP1)
Ceramide-activated protein kinase
Protein kinase C zeta
Rb dephosphorylation
?
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Growth arrest
inflammation
?
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• Lipids as receptor agonists
• Platelet-activating factor
• Lysophosphatidic acid
• Sphingosine phosphate
• Lipopolysaccharide

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• Platelet-activating factor (PAF) or
• 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine
• an ether analogue of phosphatidylcholine
• causes aggregation of platelets at picomolar
  concentrations
• acts through a G-protein coupled receptor

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Model of G-protein coupled receptor (PAF
receptor) signal transduction
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• Lysophosphatidic acid or 1-acyl-sn-glycerol-3-phos
  phate (LPA)
• metabolite of phosphatidic acid
• is an important serum mitogen
• acts through the EDG family of G-protein coupled
  receptors

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• Sphingosine phosphate
• Synthesized by sphingosine kinase
• Acts through the EDG family of G protein coupled
  receptors
• Also considered to be mitogenic

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Bacterial cell wall organization
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