Inhibition of α-amylases by pentagalloyl glucose Kinetics, molecular dynamics and consequences for starch absorption Camila Gabriel Kato-Schwartz.pdf

该【Inhibition of α-amylases by pentagalloyl glucose Kinetics, molecular dynamics and consequences for starch absorption Camila Gabriel Kato-Schwartz 】是由【小舍儿】上传分享，文档一共【9】页，该文档可以免费在线阅读，需要了解更多关于【Inhibition of α-amylases by pentagalloyl glucose Kinetics, molecular dynamics and consequences for starch absorption Camila Gabriel Kato-Schwartz 】的内容，可以使用淘豆网的站内搜索功能，选择自己适合的文档，以下文字是截取该文章内的部分文字，如需要获得完整电子版，请下载此文档到您的设备，方便您编辑和打印。JournalofFunctionalFoods44(2018)265–273ContentslistsavailableatScienceDirectJournalofFunctionalFoodsjournalhomepage:ate/jffInhibitionofα-amylasesbypentagalloylglucose:ics,molecularTdynamicsandconsequencesforstarchabsorptionCamilaGabrielKato-Schwartza,FabrícioBrachtb,GefersondeAlmeidaGon?alvesa,AndréiaAssun??oSoaresc,TatianeFrancielliVieiraa,TatianeBrugnarid,AdelarBrachta,d,?RosaneMarinaPeraltaa,d,aProgramforPostgraduateStudiesonFoodSciences,UniversidadeEstadualdeMaringá,87020-900Maringá,PR,BrazilbDepartmentofPhysicalChemistry,UniversidadedeCampinas,Campinas,SP,BrazilcProgramforPostgraduateStudiesinMedicinalPlantsandPhytotherapics,UniversidadeParanaense,Umuarama,PR,BrazildDepartmentofBiochemistry,UniversidadeEstadualdeMaringá,87020-900Maringá,PR,BrazilARTICLEINFOABSTRACTKeywords:Pentagalloyl-glucose(PGG)occursinmanyplantsandpossessesseveraltherapeuticproperties,includinganti-,theinhibitoryactionofPGGonα--(pancreaticenzyme)plexationthatise?ectivelyallowed(salivaryMoleculardockingpetitiveinhibition).Thiscontrastswithapreviousreportonthesalivaryenzymeshowingnon-?ectivethanacarboseasaninhibitorofα-amylasesandpresentedadi?,(Gómez,Lopez,Verardo,Segura,&Fernandez,2016).Besidestheobviousfactthatconsumptionofthemangopulpalsoim-Pentagalloylglucose(PGG;1,2,34,6-penta-O-galloyl-β-D-glucose)pliesautomaticallyintheconsumptionofPGG,theseed,whichisisapolyesterofglucosewith?vegallicacidmoleculesandistheusuallydiscarded,-poundinthebiosyntheticpathwayofhydrolysabletanninspoundforthepreparationofdietarysupplements,forexample.(Zhang,Li,Kim,Hagerman,&Lu,2009;Torres-al.,2017).?veesterbondsformedofAfrica,Asia,andLatinAmericafortreatingseveraldiseases,mostlybetweencarboxylicgroupsofgallicacidsandthehydroxylgroupsoftropical,arenowknowntocontainPGG(Torres-al.,2017).,numerousstudieshavecon?rmedthatPGGexertsseveralstructureoftannicacids(Zhangetal.,2009;Torres-al.,2017).therapeuticandpharmacologicale??ectsincludeanti-cancerThelistofplantsthatcontainsigni?cantamountsoffreePGGisrela-(Kant,Yen,Lu,Lin,&Chen,2016),anti-in?ammatory(Kiss,Filipek,tivelylongandincludesspeciesbelongingtothefamiliesMyrtaceae,Barbara,&Naruszewicz,2013),anti-microbial(Yongetal.,2015),anti-Anacardiaceae,Meliacea,Myrtaceae,Geraniaceae,Paeoniaceae,Faba-allergic(Kimetal.,2015),anti-viral(al.,2016),anti-oxidantceae,SapindaceaeOnagraceae,bretaceaeand(Shaikhetal.,2016),andanti-diabetic(Mohan,Viswanatha,Savinay,Lamiaceae(Zhangetal.,2009;Torres-al.,2017).InspeciesRajendra,&Halemani,2013)-oxidantactivityoffromthesefamiliesPGGhasbeenfoundinseeds,fruits,leaves,?owers,poundpresentsmorehydroxylgroupsstems,-urringphenolicanti-(Torres-al.,PGGisoneofthemostpotentanti-oxidantsamongthetannins2017).Theseedsofmango(Mangiferaindica),forexample,contain(Abdelwahedetal.,2007;Kimetal.,2015).,-diabeticactivityisrootedinthe?Correspondingauthorat:ProgramforPostgraduateStudiesonFoodSciences,UniversidadeEstadualdeMaringá,87020-900Maringá,PR,-mailaddresses:******@,rosanemperalta@().https:///?.;Receivedinrevisedform12March2018;Accepted16March20181756-4646/?-(2018)265–-amylase(TypeVI-B),humansalivary-amy-OOOlase,acarbose,potatostarchandtannicacidwerepurchasedfromOHSigma--O-galloyl--D-glucose(PGG)waspreparedbymethanolysisoftannicacidasdescribedelsewhere(Lietal.,2011).Brie?y,theme-OHthanolysissolution(800mLmethanol,360mLsodiumacetatebu?er,,pH5)°(5×500mL)(5×100mL)(essivesteps)-crystallizedfroma2%-amylaseandOthehumansalivaryα-amylasewerecarriedoutat37°Cin20mMHO?OHOHphosphatebuer,,(PGG;1,2,3,4,6-penta-O-galloyl--D-(potatostarch,–)andPGG(upglucopyranose))?cactivityofbothenzymeswas500units/mgpro----induceddiabetesinC57BL/6mice(al.,2013).Ithasbeenresultingfromthestarchhydrolysiswereassayedbythe3,5-dini-alsoclaimedthatPGGcanstimulateglucosetransportinadipocytes,trosalicylicacid(DNS)method,usingmaltoseasstandard(Miller,reducebloodglucoseandinsulinlevelsinbothdiabeticandobesean-1959).Thealdehydegroupofreducingsugarsconverts3,5-dini-?ectshavebeenattributedtoinsulinmimetics(Ren,trosalicylicacidto3-amino-5-nitrosalicylicacid,whichisthereducedHimmeldirk,&Chen,2006).Besidestheseratherintracellularme--amino-5-nitrosalicylicacidinreaseschanismsofthepossiblePGGanti-diabeticaction,thereisanotherac-,--amylaseatrelativelylowconcentrationsα(Gyémántetal.,2009).Inhibitionof-?ttingstarchhydrolysisduringdigestionand,consequently,diminishestheursafterastarch--maximalαThisphenomenonhasbeendemonstratedforseveralinhibitorsof-inhibitorconcentrations(IC)wasdoneusingtheScientistSoftwareα50amylases,notonlyforacarbose,whichistheclassical-amylasein-fromMicroMathScienti?cSoftware(SaltLakeCity,UT).Thesamehibitor,urringtannins(Silvaetal.,2014;programwasusedfor?ttingtherateequationstotheexperimentalLinks,Taylor,Kruge&Taylor,2015;Katoetal.,2017).Theinhibitoryinitialratesbymeansofaniterativenonlinearleast--amylasewaspreviouslyin-Thedecisionaboutthemostadequatemodel(equation)wasbasedonβvestigatedusingthesyntheticsubstrate2-chloro-4-nitrophenyl-4-O--themodelselectioncriterion(MSC)andonthestandarddeviationsofD-galactopyranosyl-maltoside(Gyémántetal.,2009).Itisimportant,,whichcorre-however,tocharacterizetheinhibitionofthisenzymeaswellasthespondstothenormalizedAkaikeInformationCriterion(Akaike,1974),possibleinhibitionofitspancreaticanaloguewiththenaturalsubstrate,isde?nedas:,wedecidedtoexamineindetailtheαn2icsoftheinhibitionofbothsalivaryandthepancreatic-amylases?∑i=1wYiobsobs()i?Y?2pMSC=ln?,moleculardynamicssimu-?∑nwY?Y2?n?i=1iobscal()ii?(1),invivoexperi-Yobsaretheexperimentalreactionrates,Yobsisthemeanexperimentalmentsweredoneinratsaimingat?ndingoutifinhibitionoftheα-reactionrate,Ycalisthetheoreticallycalculatedreactionrate,wistheamylasesbyPGGise?ectiveornotindiminishingthehyperglycemicweightofeachexperimentalpoint,nisthenumberofobservations,,-(2018)265–273deviationsoftheestimatedparameterswasconsideredthemostap-(Onufriev,Bashford,&Case,2004).Aper-residueenergyde-propriatedescriptionoftheexperimentaldata,positionschemewasusedtoobtaineachresidue’–250gwereusedinallex-Theproteinstructurechosentoevaluatetherelativea?(HSA,PDBcode:-1SMD).parisonpurposes,theacarbosemoleculewaschosenasvestigations,theanimalswerekeptfortendaysunderstandarden-esstostandardpelletedfoodandwaterglycosidehydrolases(Yoon&Robyt,2003).TheHSA’sionizablere--sidueswereassignedtheirprotonationstateswiththepropkaprogramperimentsinvolvingratsweredoneinconformitywiththeworldwide(Olsson,S?ndergaard,Rostkowski,andJensen(2011)).eptedethicalguidelinesforanimalexperimentationandapprovedchoicewastheoptimalpHvalueforactivity,,á(Protocol8119260115-CEUA-UEM).aligningtheresolvedcrystalbackbonestructureofthehumanpan-Ratsweredividedinto5groups(n=4ratspergroup).TogroupIcreaticalpha-amylase(PDBcode:1B2Y)(mercialcornstarch(1gperkgbodyweight)(negativecontrol)receivedonlymixedschemeofSteepestDescent/ConjugateGradient(SD/CG)(Caseetal.,2016).Boththeplusacarbose(50mg/kg).GroupsIVandVreceivedintragastricallyacarbose,modeledwitha+1charge,mercialcornstarchplusPGGdosesof50and100mg/kg,respec--(Caseetal.,2016).ThechargeswerederivedusingtheAM1-BCCferredfromliteraturedata(Ikarashi,Takeda,Ito,Ochiai,&Sugiyama,chargemodelandtheatomtypeswerethoseofthegeneralAMBER2011;Silvaetal.,2014).Fastingbloodglucoselevelsweredeterminedforce?eld(GAFF)(Wang,Wolf,Caldwell,Kollman,&Case,2004;beforetheadministrationofstarchandα-amylaseinhibitors(0time).Jakalian,Bush,Jack,&Bayly,2000).-Chek??exibleligandprotocols(Brozelletal.,2012;.,2015).ThestandardDOCKprotocolforthegenerationofdockingsurfaceandthesurfacesphereswithinthebindingsiteoftheTheerrorparameterspresentedinthegraphshowinginvivoex-acarbosemoleculewasused(Brozelletal.,2012).(Meng,Shoichet,&Kuntz,1992)?resolu-signi?cancewasdonebymeansofmultiplevarianceanalysistionenergygridwithinthebo