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LIPIDSANDBIOLOGICALMEMBRANESHLeeYuJsuicoJunsay
DepartmentofChemistry
SchoolofScienceandEngineering
AteneodeManilaUniversity1
Lipidsareallwaterinsolublebiomoleculesasidefromcarbohydrates,proteinsandnucleicacids.
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FaGyacidbased Non‐faGyacidbased
FATTYACIDBASEDLIPIDS
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Fa8yacidsarecarboxylicacidswithlong,unbranchedaliphaLcchain.
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SaturatedFa8yacids–Nodoublebonds
Fa8yacidsarecarboxylicacidswithlong,unbranchedaliphaLcchain.
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UnaturatedFa8yacids–presenceofdoublebonds.
Monounsaturated–betweenC9andC10.
Fa8yacidsarecarboxylicacidswithlong,unbranchedaliphaLcchain.
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Fa8yacidsarecarboxylicacidswithlong,unbranchedaliphaLcchain.
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HO
O
Linolenicacid
9 10 12 13 15 16 ω
ThecarbonchaindictatesphysicalandchemicalproperLesoffaGyacids
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Fa8yAcid Condensed Solubility(g/LsoluHon) MP
Caprylic C8:0 0.7 16.7
Capric C10:0 0.15 31.6
Lauric C12:0 0.055 44.2
MyrisLc C14:0 0.02 53.9
PalmiLc C16:0 0.007 63.1
Stearic C18:0 0.003 69.6
Oleic C18:1(cis) 16.2
Elaidic C18:1(trans) 43.7
Linoleic C18:2 ‐5
hGp://www.cyberlipid.org/cyberlip/home0001.htm
ThecarbonchaindictatesphysicalandchemicalproperLesoffaGyacids
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COOH: CanreactwithbasestoformSOAPS
-O
O
Na+
Polarhead Non‐polartail
AggregaLontoformmicelles
Iodinevaluetest
ThecarbonchaindictatesphysicalandchemicalproperLesoffaGyacids
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HO
O
Linolenicacid
Alkenes: CanreactviaelectrophilicaddiLon CanreactviaoxidaLon/reducLonreacLons
SuscepLbletoAUTOOXIDATIONwhenexposedtoair!OXIDATIVERANCIDITY
O
O
FaGyacidsmaybereactedwithAlcoholstoformesters.
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Beeswax Carnauba Leafwax
WAXES:ESTERSofFATTYACIDSandLONGALCOHOLS
AcylglycerolsareestersoffaGyacidwithglycerol.
1‐Monoglyceride2‐Monoglyceride1,2‐Diglyceride1,3‐DiglycerideTriglyceride
=FATS
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13
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Triglyceridescanbedegradedinthepresenceofwater:HYDROLYTICRANCIDITY.
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AddiLonofBasescanalsocleavetheesterlinkagetoformglycerolandsoaps:SAPONIFICATION.
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Doublebondsmaybehydrogenatedtoformsaturatedfats(butthisisusuallyincomplete)resultsintotransfats.
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Doublebondsmaybehydrogenatedtoformsaturatedfats(butthisisusuallyincomplete)resultsintotransfats.
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Lipidscanhavechargedorpolarparts,creaLngamphiphilicmolecules.
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Phospholipidsarelipidsthatcontainaphosphategroup
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Phospholipidsdifferontheirpolargroups
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Phospholipidsdifferontheirpolargroups
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Sphingolipidsarelipidsthathavethesphingosinebackbone
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Becauseoftheirshape,phospholipidsformbilayersinsteadofmicelles
NON‐FATTYACIDBASEDLIPIDS:ISOPRENOIDS
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Isoprenoidsmakeupanotherclassoflipids.Theyarecomposedofisopreneunits.
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Isoprenoidsaregroupedaccordingtohowmanyisopreneunitsmakeupthecompound
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No.ofIsopreneunits Name
1(C5) Hemiterpenes
2(C10) Monoterpenes
3(C15) Sesquiterpenes
4(C20) Diterpenes
6(C30) Triterpenes
SterolsandSteroidsarederivedfromTriterpenes.Amongthemostfamousoftheseischolesterol.
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Whilecholesterolisanintegralpartofthecellmembrane,italsoservesasaprecursortohormonesandbileacids.
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Plantsalsohavesimilarsterolmoleculescalledphytosterols.
Theyaresaidtolowercholesterollevelsinblood.
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EICOSANOIDSANDOTHERLIPIDS
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Eicosanoidsarederivedfromarachidonicacidandhavehormone‐likeacLvity
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COX‐1:consLtuLveCOX‐2:inflammatoryresponse
UseofNSAIDs
Eicosanoidsarederivedfromarachidonicacidandhavehormone‐likeacLvity
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Eicosanoidsarederivedfromarachidonicacidandhavehormone‐likeacLvity
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Pheromonesaresignalingsubstancesthatarereleasedbyoneorganismtoalterthebehaviorofanotherorganism
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ElectroncarriersareimportantmoleculesforenergyharvesLngfromelectrons(intheelectrontransportchainandphotosynthesis)
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ElectroncarriersareimportantmoleculesforenergyharvesLngfromelectrons(intheelectrontransportchainandphotosynthesis)
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FATSANDHEALTH
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FuncLonsofFats• Usedtobuildcellsandpartsofthecell(e.g.braincells,nerve
Lssues,cellmembrane)
• StoredinthebodyinadiposeLssue– AdiposeLssuearecalledfatdepots
• Surroundvitalorgans(e.g.heart,kidney,spleen)toserveasprotecLvecushion
• StoredundertheskinforinsulaLon• FatreservesareconvertedtoglycerolandfaGyacids(9kcal
pergram)– Glycerolisburnedforenergyorconvertedtoglucose
Thehumanadipocyte
• ComposeadiposeLssue• Forstorageandsynthesisof
triacylglycerides,insulaLon,energystorage(higherenergycontentthanglycogen)
• Whitefatcells:lipiddropletwithperipheralcytoplasmandnucleus;semi‐liquidfatwithsomesterolderivaLves
• Brownfatcells:lipiddropletsscaGered,highmitochondriacontent
www.cnrs.fr,www.vulgaris‐medical.com
40
FatsTransport• Someimportantbloodlipoproteins– Groupofproteinswithatriglycerideorcholesterol
– Very‐lowdensitylipoprotein(VLDL)• TransportnewtriglyceridesfromlivertoadiposeLssue
– Lowdensitylipoprotein(LDL)• Transportcholesterolfromlivertocells
– Highdensitylipoprotein(HDL)• TransportcholesterolfromLssuestoliver
Atherosclerosis:Notjustasimplecloggingproblem!
From:hGp://www.nia.nih.gov/NR/rdonlyres/C3B176CB‐3173‐4F89‐8FDA‐2774FB751108/4227/pic_atherosclerosis.jpg
Cholesterolbiosynthesis
From:hGp://banon.cshl.edu/cgi‐bin/eventbrowser?DB=gk_current&FOCUS_SPECIES=Homo%20sapiens&ID=191273&
Loweringcholesterolsynthesis
• Usehypolipidemicdrugs(eg.StaLns)• STATINSareHMG‐CoAinhibitors– Eg.LovastaLn
Tablefrom:hGp://en.wikipedia.org/wiki/StaLn
CriscoandOlestra(byP&G)
1911:Shortening
“Toeat,ornottoeat‐fatistheques1on.”‐fromtheIntroduc1onofMaryEnig,KnowyourFats:TheCompletePrimerforUnderstandingtheNutri1onofFats,Oils,andCholesterol,BethesdaPress,USA,2000.
Olestra• 1998,ProctorandGambleintroducedanewfat/oilsubsLtutecalledOlestra(brandnameOlean®
• materialreplacesfatsinsnackfoodssuchaspotatochips
• claimedthatfoodusingOlestrainplaceofdigesHblefatsprovidelesscaloriessincetheOlestraisnotdigestedandpassesthroughthebodyunchanged
• Somesideeffectsincludeabdominalcrampingandloosestools
Olestra
HowdoesOlestrawork?
hGp://www.cnn.com/HEALTH/9802/10/fakefat.olestra/olestra.large.jpg
Olean®
Olean®
hGp://staLc.howstuffworks.com/gif/quesLon526‐fat‐chips.jpghGp://staLc.howstuffworks.com/gif/quesLon526‐olestra‐chips.jpg
CarniLneCraze
• ResponsibleforfaGyacidtransportfromcyosoltomitochondriawheretheFAismetabolised
• NaturallysynthesizedfromLysandMet(L‐isomer)inliverandkidneys
ImagefromhGp://en.wikipedia.org/wiki/Image:Acyl‐CoA_from_cytosol_to_the_mitochondrial_matrix.gif
CarniLneCraze• Highestamountinmeat,dairy,nuts• Healthyindividuals,includingstrict
vegetarians,generallysynthesizeenoughL‐carniLnetopreventdeficiency.
• TherolesofL‐carniLnesupplementaLonasanadjuncttostandardmedicaltherapyinmyocardialinfarcLon,heartfailure,anginapectoris,Alzheimer'sdisease,andHIVinfecLonrequirefurtherresearch.
• Althoughrecentstudiesinratssuggestacetyl‐L‐carniLnesupplementaLonmaybebeneficialinprevenLngage‐relateddeclinesinenergymetabolismandmemory,itisnotknownwhetheracetyl‐L‐carniLnesupplementaLonwillhelppreventsuchage‐relateddeclinesinhumans.
• ThereisliGleevidencethatL‐carniLnesupplementaLonimprovesathleLcperformanceinhealthypeople.
Infofrom:hGp://en.wikipedia.org/wiki/CarniLne,TheLinusPaulingInsLtute(OregonStateUniversity).hGp://lpi.oregonstate.edu/infocenter/othernuts/carniLne/
53
BIOLOGICALMEMBRANES
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Biologicalmembranesservesmanypurposes:
1. Physicalbarrier2. SelecLvefilter3. CommunicaLon4. Energymanagement
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Biologicalmembranesaresupramolecularassembliesofproteins,lipidsandcarbohydrates.
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Biologicalmembranesaresupramolecularassembliesofproteins,lipidsandcarbohydrates.
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Lipids:PhospholipidsSphingolipidsSterolsGlycolipids
Proteins:IntegralproteinsPeripheralproteinsGlycoproteins
Lipidbilayersmakeupthemainmatrixormembraneenvironment.
58
Liposomes:phospholipidbilayers
MembranesaremadeupmostlyofphospholipidswhichcanfreelymoveinalateraldirecLon(FLUID).
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PhospholipidcomposiLonofthemembraneisasymmetrical.
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Otherlipidmoleculesgiverigiditytothemembrane
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Otherlipidmoleculesgiverigiditytothemembrane
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Otherlipidmoleculesgiverigiditytothemembrane
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Otherlipidmoleculesgiverigiditytothemembrane
MembranelipidsallowfordynamicacLonsofmembranes
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Integralproteins:spansthemembrane(monolayerorbilayer)
Peripheralproteins:noncovalentlybondedtointegralproteins
IntegraLonofproteinsmaybeviaalphahelices,betabarrelsorcovalentlinkagetolipids
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BecauseofthisfluidcombinaLonofdifferentmolecules,thecurrentlyacceptedmodelformembranesistheFluidMosaicModel.
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MEMBRANETRANSPORT
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Membranesregulatetheflowofmoleculesinandoutofthecell
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Studiesusingtheplanarbilayersshowthatmembraneshaveverylowpermeabilitytoionsandmostpolarmolecules
70
• Thepermeabilitycoefficientsofsmallmoleculesarecorrelatedwiththeirsolubilityinanonpolarsolventrela8vetotheirsolubilityinwater(KD)
• Totraverseamembrane,asmallmolecule
1.shedsitssolvaLonshellofwater
2.becomesdissolvedinthehydrocarboncoreofthemembrane
3.diffusesthroughthecore
4.becomesresolvatedwithwater
MembranesallowpassiveandacLvetransportofmolecules
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Passive:noenergyneededAcHve:needsATP!
MembranesallowpassiveandacLvetransportofmolecules
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Passive:noenergyneededAcHve:needsATP!
Proteinmediatedpassivetransport(alsocalledfacilitateddiffusion)maybeofdifferentmodes
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Aquaporinsfacilitatediffusionofwateracrossthemembrane
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AcLvetransportneedsenergy.UsuallyittransportsmoleculesfromregionsoflowconcentraLontoregionsofhighconcentraLon.
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AcLvetransportneedsenergy.UsuallyittransportsmoleculesfromregionsoflowconcentraLontoregionsofhighconcentraLon.
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AcLvetransportneedsenergy.UsuallyittransportsmoleculesfromregionsoflowconcentraLontoregionsofhighconcentraLon.
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AcLvetransportneedsenergy.UsuallyittransportsmoleculesfromregionsoflowconcentraLontoregionsofhighconcentraLon.
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ProtonpumpsinthemitochondriaaredrivenbyhighenergyelectronswhileATPsynthaseisapassivetransportsystemthatcounteractsanimbalanceof+chargeononesideofthemembrane.
79