KnowYourInner:AllaboutLipids

Haveyoueverthoughtunderstandinglipidswasasimpletask…untilyoutriedtotackletheexamquestions?Thistutorialwillmainlyserveasaguidedoutlinetocomprehendingandcompletingthetoughestandmostintensivequestionsaboutlipids.

PartA:WhatisaLipid,Anyway?Bydefinition,alipidis“an[organic]moleculeofbiologicaloriginthatissolubleinsolventsoflowpolarityandinsolubleinsolventsofhighpolarity.”1

Atfirstglance,thereseemtobemanycomplexpartstothisdefinition,solet’sbreakitdown:

First,alipidisanorganicmolecule,meaningthemoleculemustcontaincarbon.Furthermore,lipidsarebiomolecules,meaningthattheyderivefrombiologicalorigins(ie.aresynthesizedbyalivingorganism).Assuch,atitsmostbaselevel,themolecularformulaforlipidswillcontaincarbons,hydrogens,andoxygens.

Secondly,lipidsaresolubleinsolventsoflowpolarity,whichsimplymeansthatlipidsaresolubleinnonpolarsolvents.Thissolubilitypropertyisaresultofthelargenonpolarregionsthatareindicativeofthelipidmolecule.

HOWCANYOUDISTINGUISHALARGENONPOLARREGION?

Longhydrocarbonchainsinlipidmoleculesdevelopthelargelynonpolarregionalpropertyoflipids.Duetocarbonandhydrogenformingnonpolarbondsduetotheirlowelectronegativedifference(asopposedtoOxygen‐Hydrogen,whichhaveahighelectronegativedifferenceandarethuspolar),alargehydrocarbonchainorringcreatesanonpolarregion.

Forexample:PHOSPHOLIPID

NONPOLARREGION

Anotherexample:STEROIDS

FATTY

Thelargehydrocarbonrings,methylgroups,andhydrocarbonchainsallconsistofnonpolarC‐Hbondsduetoitslowelectronegativedifference,andassuchcontributedtoitsnon‐polarity.

Whenfinalsdayapproaches,itwillbeimportanttounderstandwhatareasofthelipidmoleculecontributetoitsnon‐polarity,sotakeheed!

What’sthesignificanceofthenon‐polarity/lowpolarity?

Themostsimplistic(andnotentirelychemicallytrue)rule‐of‐thumbisthat“likedissolveslike”,whichindicatesthatasolutewilldissolveinasolventofidenticalpolarproperty,buttwosubstancesofopposingpolarpropertieswillnotinteract.Forexample,anonpolarmolecule(ie.afattyacid)willnotdissolveinapolarsubstance(ie.water),andviceversa.

Assuch,thirdly,lipidsareinsolubleinwater(apolarmoleculeduetothehighelectronegativeO‐Hbonddifference),fornon‐polarmoleculesareinsolubleinpolarmolecules.Thus,thepresenceofanonpolarmolecule(orregionofmolecule)meansthattheregionormoleculeishydrophobic(Greek,“waterfearing”),andproducesahydrophobiceffect,“whichcausesthepolarendstobeorientedoutwardstowardsthesolventandthenonpolarregionsorientedinwardsawayfromthepolarsolvent.”2,whenincontactwithapolarsolvent(ie.solvent),makingthenonpolarmoleculeisinsolubleinwater.Thistermisinterchangeablewithlipophilic(Greek,“fatloving”),indicatedthatnonpolarlipidsaresolubleinothernonpolarsolvents.

Thus,polarmoleculesareconsideredtobehydrophilic(“waterloving)andlipophobic(“waterfearing”),duetotheabilityofhighlypolarbondsbeingsolubleinpolarsolvents,andinsolubleinnonpolarsolvents(ie.fats,lipids).

However,therearecategoriesoflipidsthatarebothhydrophobicandhydrophilic.Theselipidsarecalledamphiphiles,moleculesthatcontainbothlargeareasofpolarityandnonpolarity,andarethusbothhydrophilicandlipophilic.Phospholipidshavebothalonghydrophobichydrocarbontail,andahydrophilichead,givingphospholipidsintegralbiologicalproperties,whichwillbelaterdiscussed.

SUMMARY,PLEASE!:Lipidshavelargenonpolarregionsderivingfromnonpolarhydrocarbonbonds(whichhavelowelectronegativedifference).Thus,lipidsarelargelyinsolubleinpolarsolvents(water),andaresolubleinnonpolarmolecules.Assuch,thenonpolarregionsarehydrophobic/lipophilic,andthepolarregionsarehydrophilic/lipophobic.

Part2:WhataretheDifferentkindsofLipids?Thereare8majorclassificationsoflipids(with7ofthembeingimportantforthepurposeofChem14C)

1. FattyAcids

2. Waxes

3. Triacylglycerides

4. Phospholipids

5. Prostaglandins

6. Steroids

7. LipophilicVitamins

8. Terpenes(plant‐basedlipids)

Part3:HowintheworlddoItelltheselipidsapart?Thissectionwillbethemostinvaluabletoyoufortheexam.Mostexamquestionsfrompreviousyearscenteronhowtodistinguishandclassifytypesoflipids,andtheimportantdefinitionsbehindsaidmolecules.

FattyAcids:

Fattyacidsarelipidsthatconsistof(1)Carboxylicacid(‐COOH)witha(2)long,un‐branchedhydrocarbonchain.

Example:Arachidicacid(C20H40O2)

CARBOXYLICACID(‐COOH)LONGUNBRANCHEDHYDROCARBONCHAIN(C‐H)

Fattyacidscommonlyhavethefollowingcharacteristics(besuretolookforthesepropertiesontheexam)

‐ Evennumberofcarbons(ex.arachidicacidhas20carbons).Themostcommonfattyacidsconsistof12‐20carbons,whilethemostbiologicallyimportantfattyacidshave18carbons(forexample,stearic,oleic,andlinoleicacids)

‐ Actasabasic“buildingblock”formorecomplexlipidmolecules(actasaprecursortootherlipids).Forexample,thelonghydrocarbonchainprovidesanessentialnonpolarregionforthehydrophobictailofphospholipids;waxes,triacylglycerides,andphospholipidshaveatleastonefattyacidasanattachment.

‐ LowpolarityduetothelowelectronegativedifferenceintheC‐Hbondsofthelonghydrocarbonchain,producingahydrophobiceffect.

Furthermore,fattyacidscanbedividedintotwosubcategories:saturatedandunsaturated.ThisismaincategorizedbythepresenceofC=Cbondsinthehydrocarbonchain.SaturatedcarbonshavefullC‐Hbondsinthehydrocarbonchain,andassuchhavenonC=Cbonds.Unsaturatedcarbons,however,haveatleastoneC=Cbond(monounsaturated,morethanoneispolyunsaturated)inthechaintoreplacetwohydrogenC‐Hbonds.

Withinunsaturatedfattyacids,cis‐C=Cbonds(Carbonbondsareonthesameside)aremuchmoreprevalentthantrans‐C=Cbonds(carbonbondsonoppositesides)innature.“Trans‐fats”arenotaseasilymetabolizedbycatalyticenzymesascis‐fats,andareleftuncatalyzedandcandamagehealth(plaquebuildup).

Waxes:

Waxesare(1)estersthathaveattached(2)afattyacidand(3)along‐chainalcohol.Thesynthesisofwaxesusuallyderivesfromthedehydrationsynthesisofafattyacidandalong‐chainalcoholgroup.

Duetothelowpolaritycausedbythetwolonghydrocarbonchainsoneithersideoftheesterlinkage,waxesarehighlyinsolubleinpolarsolventsandarehydrophobic;extremelyrepellenttowardwater.Asaresult,themajorbiologicalfunctionwaxesaretoactasawaterbarrier(ie.birdfeathersarecoatedinwaxlipids,whichminimizeswettingofthefeathers,leavesarecoatedinwaxtopreventtheevaporationofwater,damagingplantnourishment.

Myricyl cerotate Present in beeswax, carnauba

wax

ESTER

Long‐chainalcohol(‐OH)

Fattyacid

Triacylglycerols:

Triacyglycerols,ortriacylglycerides,arelipidssimilartothatofwaxes(inthattheycontainesterandanalcohol‐likefunctiongroup),butconsistof(1)atriester,(2)afattyacid,and(3)glycerol,orglycerin,athreecarbonalcoholstructure:

Glycerolandthefattyacidundergodehydrationsynthesis,whichinturncreatesthetriacylglycerolmolecule.

Where“R”indicatesthelong,un‐branchedhydrophobictailofhydrocarbonsthatarerepresentativeofthefattyacid.

Triacylglycerolshavethefollowingimportantcharacteristics

‐ Varyingmeltingpoints.Ifsolidatroomtemperature,thenthelipidisconsideredafat,ifliquidatroomtemperature,oil.

‐ Themostabundantnaturallysynthesizedlipid.‐ Itsmainbiologicalfunctionisforenergystorage(ie.consumptionoffatsprovidesaslowburninglong‐

termstorageofenergythatcanbemetabolized).‐ Withtheadditionofwaterinahydrolysisreaction,the“breaking”offatsderivedfromanimalsyields

soaps,whicharehydrophilicCO2‐groupsattachedtoahydrophobichydrocarbonchain.

Glycerol Fatty acids

Triacylglycerol

HOWDOSOAPSWORK?

1. Thepolar,hydrophilicheadofsoap(CO2‐)isattractedtothepositivelychargedendsofwater,whilethe

hydrophobichydrocarbontailcanavoidthewater.2. Thishydrophobic,lipophilictailthencanattachtodirts,fattyacids,andotherlipids,duetotheirlow

polarity.3. Thesetailssurroundthe“dirts”inspherescalledmicelles,whichisolatethedirtandremovethem

frominteractionwiththewatermolecules.4. Finally,whenthewaterisremoved,themicellesencapsulatingthedirtarecarriedaway,leavingthe

areafreeofthedirts.

Phospholipids:

Aphospholipidsimilarlyconsistsof(1)glycerol,three‐carbonalcoholstructureswhichthenformsan(2)triesterwith(3)twofattyacidsand(4)onephosphategroup

Genericexample:

Where“R”representsthelongun‐branchedhydrocarbonchainrepresentativeofafattyacid.

Phospholipidshavethefollowingkeyproperties:

‐ Secondmostabundantnaturallysynthesizedlipid‐ Itsmajorbiologicalfunctionistoformaintegralphospholipidbilayerinthecellmembraneofliving

organisms,acriticalcomponentthatallowsfortheselectivediffusionofionsandmoleculesthroughthebarrier

HOWDOESTHEPHOSPHOLIPIDBILAYERWORK?

Twophospholipidsfaceapartfromeachother,thepolar,hydrophilicheadofthephosphategroupfacingoutwards,andthehydrophobic,hydrocarbonchainonthefattyacidsfacinginwards.Thiscreatesthehydrophobiceffectofthetails,avoidingwater.Thisbilayerofthecellmembraneallowsforthecelltofreelymovethroughwater,yetmaintaintheinternalstructureofthecell

Phosphategroupester

2Fattyacidesters

Prostoglandins:

Prostoglandinsarelipidmoleculesthatcontaina(1)prostanoicacidskeleton,whichconsistofa(2)cyclopentaneringattachedtoaupperchainofa(3)fattyacidwithsevencarbons,andalower(4)long,unbranchedchainofhydrocarbons,with8carbons.

Ex.ProstaglandinF2alpha

Thenomenclatureofprostaglandinsisdependentonthestereochemistryofthelipid,basedonthenumberofOH,C+C,andC=Ogroupsinthemolecule.

Majorcharacteristicsofprostaglandinsinclude:

‐ Majorbiologicalfunctiontoactasaregulatorandsignalmolecule(regulationofhormones,inflammation,calciummovement;controlofcellulargrowth;constrictionofsmoothmusclecells;regulationofplateletgrowth;spinalneuronsensitization)

‐ Prostoglandinsoftensynthesizeatwoundsitestoregulateandsignalaninflammatoryresponse,leadingtoinflammation.

‐ Shorthalf‐lifefromorigination,about5minutesorless.‐ Whileeachstructurehasthesameprostanoicacidskeleton,thedifferingstereochemistryofeach

prostaglandinderivesvastlydifferingbiologicalfunctionsforeachlipid.

Prostaglandin F2α (PGF2α

)

Upperchainoffattyacids

Lowerchainofhydrocarbons

Cyclopentane

ring

Steroids:

Steroidmoleculesconsistofabasic(1)4‐carbonringskeletonformingaflatcore.

Examplesofsteroidsinclude:cholesterol,testosterone,estrone,cortisone,aldosterone,corticoidhormones,bileacids,andcholicacids.

Whileallsteroidshaveaverysimilarcarbonringskeletalstructure,thevariousfunctiongroupattachmentsgivesteroidsaverywiderangeoffunctions.

Abbreviatedlistofbiologicalfunctions:

1. Hormones:chemicallyregulatethebodya. Testosteroneandestrone,sexhormones,regulatethesexualdevelopmentoforganismsb. Corticoidsteroids/hormones,regulatethemetabolicprocessesofthebodyc. Cortisone:regulatesthebodyinflammatoryresponse,glucosemetabolismd. Digestive:emulsifiesfatsinintestinestoaidinthedigestiveprocess,integralcomponentofbile

acid.

Biosynthesisofsteroidsisalongandcomplexprocess,startingfromAcetylCoenzymeA;variousenzymaticstepsformintermediatesteroidmolecules,formingcholesterolattheend.

Cholesterolistheprecursortoallvertebratesteroids,themostbasicsteroidbiologicallyproducedbylivingorganisms.

LipophilicVitamins:

First,vitaminsareorganiccompounds(containingcarbon,hydrogen),thatarenotclassifiedasfats,proteins,orcarbohydrates,thatarerequiredforthegrowth,regulation,andmaintenanceofanimals.Thisbroaddefinitionofvitaminsthusencompassescompoundswithawidevarietyofstructuresandfunctions.

Therearetwomajorlipophilic(andthushydrophobic)vitamins:VitaminEandVitaminA(retinol)

VitaminEisamixtureofstereoisomers,mainlyconsistingofamoleculecalledalpha‐tocopherol

Withahydrophobictailcreatedbythelonghydrocarbontail.Itsmainfunctionistoprotectcellsagainstfreeradicals,unstableionswithanopenvalencethatcancauseoxidativedamagetothecells.

VitaminA(retinol)containsalonghydrophobicnonpolarhydrocarbonchain,withitsmainfunctionbeingusedinphoton‐harvestingproteins,essentialtothedevelopmentofvision.

Theeasiestmethodofdistinguishinglipophilicvitaminsfromotherlipidcategoriesisthattheyhaveastructureunlikethatofotherlipids,andcanwidelyvary.Whenindoubt,Useamethodofeliminationtorejectthepossibilityofthemoleculebeinganyotherkindoflipidfirst.

α-Tocopherol Hydrophobic antioxidant

vitamin

Part4:Finally,whatshouldIpracticethemostformytestonlipids?Thefollowingisanabbreviatedlistoftopicsyououghttorememberforthefinalexam.Thebestrecommendationistodoalloftheproblemsfrompreviousfinalexams,astheywillbemostindicativeoftherigorandextentinwhichitdelvesintolipids.

‐Moleculeswiththelargesthydrocarbonchainshavelowerpolarity,andarethusmostsolublewithfats,andinsolublewithwater.

‐Whenaskedwhichmoleculewitheasilypassthroughahydrophobicmembrane,lookforthemoleculewhichexhibitsthelowestpolarity(lowestelectronegativedifferenceinbonds,diploemoments,etc.);rememberthesimple“likedissolvelike”rule.

‐Knowinsideandoutthekeyfundamentalcharacteristicsofeachcategoryoflipid(asoutlineineachbox),andthecommonnamesofafewmoleculesofeachcategory.

‐Ifdescribingthestructurecangetconfusingforyouattimes,learninghowtodrawthebasicstructureofeachlipidwouldbeinvaluableinyouranalysisofthelipidanditsfunctionalproperties.

‐Knowthemostbasispropertiesoflipids(insolubleinwater,solubleinnonpolarsolvents,organicbiologicalmolecule)

‐Finally,whenindoubtaboutdrawingthestructureoflipidcategories,drawthemostgenericexample.

Suggestedpracticereview:Problem16,FinalExamPartA,Fall2012;Problem13,FinalExamPartA,Winter2012.Allproblemscanbefoundonhttp://www.chem.ucla.edu/harding,underPastExams.

Goodluck,anddigdeep,theanswerismostdefinitelyinyourgut.

Works Cited

Brandt, Mark. "Introduction to Lipids." Rose-Hulman.edu. Rose-Hulman Institute of Technology, 2011. Web. 9 June 2012. <http://www.rose-hulman.edu/~brandt/Chem330/Lipid_properties.pdf>. Web.

“Fatty Baby”. Picture from http://musicallmorning2.files.wordpress.com/2009/03/fattybaby.jpg. Google Images, 9 June 2012. Web.

Hardinger, Steven. "Biomolecules Survey 2: Lipids." Chemistry 14C, Lecture 1. UCLA, Young CS50, Los Angeles. 4 June 2012. Lecture. (Majority of information from this tutorial derives from this lecture)

Hardinger, Steven. Chemistry 14C: Organic Molecular Structures and Interactions : PowerPoint Lectures for Chemistry 14C with PowerPoint CD. Plymouth, MI: Hayden-McNeil, 2012. Print. (All chemical diagrams, pictures, and figures are taken from Prof. Hardinger’s Powerpoint Slides provided with the Course Supplement.)

1,2 Hardinger, Steven. “Illustrated Glossary of Organic Chemistry: A product of the Institute for Reduction of Cognitive Entropy in Organic Chemistry”. Organic Chemistry at UCLA. http://www.chem.ucla.edu/harding/ 2012. Web.