第六章脂类代谢The sixth chapter is lipid metabolism文档格式.docx

第六章脂类代谢The sixth chapter is lipid metabolism文档格式.docx

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3.masterofpalmiticacidsynthesisparts,rawmaterials,pathwaysandkeyenzymes;

familiarwithfattyacidchainlengthandsaturationtounderstandtheregulationoffattyacidmetabolism.

4.familiarwiththebiosynthesisoflecithinandbrainphospholipids.

5.familiarwiththesite,rawmaterial,processandtransformationofcholesterolsynthesis.

Introduction:

lipidisanimportantnutrientofthehumanbody,dividedintotwocategories:

fatandlipid.Themainfunctionoffatisenergystorageandenergysupply.Lipids,includingphospholipids,glycolipids,cholesterolandtheiresters,areimportantcomponentsofbiologicalmembranes,involvedincellrecognitionandinformationtransmission,andareprecursorsofavarietyofbiologicallyactivesubstances.Therearetwosourcesoffattyacidsinthebody:

first,thebodyitselfissynthesized,storedinfattissueasfat,andmobilizedfromfatasneeded.Saturatedfattyacidsandmonounsaturatedfattyacidsaremainlysynthesizedbytheorganismitself.Anothersourceofdietaryfatsupply,especiallysomepolyunsaturatedfattyacids,theanimalbodyitselfcannotbesynthesized,needtobeextractedfromvegetableoil,calledessentialfattyacids.Thischapterfocusesonthedecompositionandanabolismoffats.

Section1Introduction

Lipids

Fat（fat）,alsoknownastriglyceride（triglyceride,TG）.Fatcellsarethemajorreservoirofmammalianfat.Glycogencanbeinashorttime（about1H）isusedtoprovideenergyformusclecontraction,butsustained,intensework,suchasthemarathonrace,migratorybirdslastingflightandlocustmigration,theenergysourcedependsonthemetabolismofTG.1goxidationrelease37.6kJ,morethan2timesmorethanthesameamountofsugarorprotein.

MostnaturalfattyacidsareevennumbersC,16Cor18Carecommon;

linoleicacid,linolenicacidandpeanutfouracidsaretheessentialfattyacidsinunsaturatedfattyacids.

Phospholipidsaredividedintoglycerol,lecithinandsphingomyelinaccordingtotheirchemicalstructure.

Glycerophospholipidsarethemostcontentoflipidsinbiologicalmembranes,thecorestructureis-3-C1andglycerolphosphate,C2hydroxylgroupsare2acylsubstitutedlongchain（hydrophobictail）,phosphateandhydroxylC3withvarioussubstituentstoformthepolarhead.Includingphosphatidylcholine（lecithin,PC）,phosphatidylethanolamine（PE,PE）,phosphatidylserine（PS）,phosphatidylglycerolandphosphatidylglycerol（twocardiolipin）andphosphatidylinositol（PI）sixclasses,eachclasswithdifferentfattyacidcompositionandseveralkindsoftheredbloodcells,therearemorethan100kindsofdifferentphospholipids.Sphingomyelinandcerebrosidesandgangliosidesofsphingolipids,highercontentinnervetissueandbrain.Consistingofamoleculeoffattyacid,amoleculeofsphingosineorderivativesthereof,andapolarheadgroup.

Sterolisaderivativeofcyclopentane,phenanthreneandphenanthrene.Cholesterol（cholesterol,Ch）andcholesterolestersareimportantcomponentsofplasmaproteinsandextracellularmembrane.Cholesterolregulatesthefluidityofbiologicalmembranesandisalsotheprecursortothesynthesisofbiologicallyactivesubstancessuchasbileacids,steroids,andvitaminD.

Two.Biofilm

Theoutermembraneofcellsandtheinnermembranesystemoforganellesarecollectivelycalledbiofilms.Itsfunctionistomaintaintheintracellularenvironmentisrelativelystablebarrier,butalsoforsubstanceexchange,cellidentification,informationtransmissionsites,theinternalmembranesystemenzymestoregionaldistribution,toensurethatavarietyofbiochemicalreactionsinanorderlymanner.Thebasicstructureofthemembraneisthelipidbilayer,andisexplainedbythefluidmosaicmodel.

Three.Enzymatichydrolysisoflipids

1.lipaseisfoundwidelyinanimals,plantsandmicroorganisms.Inhumans,thedigestionoffatismainlyinthesmallintestine,catalyzedbypancreaticlipase,whichassiststhegradualhydrolysisoffatstoproducefattyacidsandglycerol.

2.phospholipasehasavarietyofesterbondsthatactondifferentpartsofthephospholipidmolecule.The1and2esterbondsarecalledphospholipaseA1andA2,

Formationoflysophosphatidicacidandfreefattyacid.Theenzymeactingonthe3position,calledphospholipaseC,actsasanenzymethatactsasanalternativetotheesterbondbetweenthephosphatesubstituentsandiscalledphospholipaseD.Theenzymeactingonthe1-pointesterbondiscalledphospholipaseB1.

3.cholesterolesterasehydrolyzecholesterolesterstoproducecholesterolandfattyacids.

4.smallintestinecanabsorbthehydrolysisproductsoflipids.Bilesaltshelpemulsifyandformapoprotein,aformofapothatisabsorbedbyintestinalmucosalcellsintothebloodcirculation.Thus,CM（chylomicron）isalipoproteinthattransfersexogenouslipids（mainlyTG）.

Catabolismofsecondsectionsoffat

Thefatinthefoodthroughthedigestivelipasewasgraduallydegradedintoglycerolandfreefattyacid（FFA）,andstoredinthefatcellsinthefatfatmobilizationinthedegradationoffatmobilization,threetriacylglycerollipaseactivityislow,theratelimitingenzymeoffatmobilization.Lipolysisisthefirststepinanorganism'

suseoffatasanenergysource.

I.oxidationofglycerol

Theglycerolproducedbyfatmobilizationismainlyproducedbytheactionofglycerolkinaseinlivercells,whichisproducedby3-,followedbythepathwayofglucosemetabolism,orbygluconeogenesis.Adiposetissueandskeletalmuscletissuescannotmakegooduseofglycerolbecauseoftheirlowactivityofglycerolkinase.

Two,theoxidationoffattyacids

Fattyacids,insolubleinwater,bindtogetherwithalbuminintheblood（10:

1）,transportthetissuesofthebody,oxidizeandbreakdowninthetissuesofthemitochondria,releaselargeamountsofenergy,andactivatetheliverandmusclesmostactively.In1904,Knooplabeledwithbenzene,tracethefattyacidsinthetransformationprocessofanimalbody,foundthatwhentheoddcarbonfattyacidderivativesweredegradedwhendetectedinurineishippuricacid,ifevencarbon,urineisphenaceturicacid.Obviouslythedegradationoffattyacylchainoccursinthebetacarbonatom,i.e.eachfromthefattyacidchaincuttingunitunderasecond.Afterthescientificexperimentsprovethatbetaoxidationtheoryiscorrect,thesecondcutunitisacetylCoA,fattyacidintomitochondriabeforebeingactivated.

（I）activationoffattyacids

Incytosol,FFAisactivatedbyesterificationwithCoA,whichcatalyzesthesynthesisoftheacylCoAsynthetase,involvingATPandMg2+.TheresultingPPiisimmediatelyhydrolyzedbythephosphatase,whichpreventsthereversereaction,sotheactivationofthe1moleculeFFAactuallyconsumes2high-energyphosphatebonds.

RCOOH+ATP+CoASH-RCO~SCoA+AMP+PPi

（two）acylCoAentersmitochondria

Theoxidationoffattyacidsiscarriedoutinmitochondria,whereasacylCoAisnotfreetoenterthestromathroughthemitochondrialmembraneandisrequiredtotransportcarnitineviamitochondriaviacarnitinetransportinthemitochondrialmembrane.TheacylcarnitineacyltransferaseCoAandII（isozymes）catalyzethetransportofacyltransportersandreleaseofcarnitine.EnzymeIisthedominantratelimitingenzymeinFFAoxidationdecomposition.

（three）betaoxidationofacylCoA

TheoxidationofacetylCoAtoacetylCoAinvolvesfourbasicreactions:

thefirstoxidationreaction,thehydrationreaction,thesecondoxidationreactionandthesulfurhydrolysisreaction.

ThefirststepiscatalyzedbyacylCoAdehydrogenasedehydrogenationofanti-Delta2-enoylCoAandFADH2.

Thesecondstepbyanti-Delta2-enoylCoAhydratasecatalyzingwatertogenerateL-（+）-betahydroxyacylCoA.

Thethirdstep,catalyzedbyL-（+）-betahydroxyCoAdehydrogenase,producesbetaketoacylCoAandNADH+H+.

Thefourthstepinvolvesthecleavageofalpha-tobeta-CbetweenthesubstrateandtheCoA,andCoASHparticipatesintheformationof1acetylCoAandlessthan2Coflipidacyl.Thenanotherroundofbetaoxidation,socyclicreactions.

（four）energycalculationoffattyacidoxidation

1moleculesofpalmiticacid（16C）after7betaoxidationcangenerate8acetylCoA,7NADH+H+,7FADH2.EachacetylCoAenterstheTCAcycle,generating3NADH+H+,1FADH2,1GTP,andreleasing2moleculesCO2.

Thetotalreactionequationis:

CoA+23O2+131Pi+131ADP,CoASH+16CO2+123H2O+131ATPhexadecanoyl

ThenumberofATPnetgeneration:

12***=12983727-2.（fattyacidactivationconsumes2high-energyphosphatebonds,whichconsume2ATP）

Whenfatisusedasenergy,theorganismalsogetsalotofwater.Thecamel'

shumpisastorehouseofstoredfatthatprovidesbothenergyandwater.

（five）otherpathwaysfortheoxidationoffattyacids

1.oxidationofanoddnumberedcarbonatomfattyacid

Thebodycontainsaverysmallamountofoddnumberedcarbonfattyacids,whilemanyplants,marineorganisms,petroleumyeasts,etc.containacertainamountofoddnumberedcarbonfattyacids.InadditiontoproducingacetylCoA,thebetaoxidationalsogeneratesa1molecule,propylCoA,whichproducessuccinateCoAviabetacarboxylaseandisomeraseandisthoroughlyoxidizedbyTCApathway.

2.oxidationofunsaturatedfattyacids

Thebodyfatacidabout