PPQ.docx
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PPQ.docx
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PPQ
Pyrroloquinolinequinone
FromWikipedia,thefreeencyclopedia
"PQQ"redirectshere.FortheIATAAirportCodePQQ,seePortMacquarieAirport.
Pyrroloquinolinequinone
Identifiers
CASnumber
72909-34-3
PubChem
1024
ChemSpider
997
KEGG
C00113
MeSH
PQQ+Cofactor
ChEBI
CHEBI:
18315
Jmol-3Dimages
Image1
SMILES
[show]
InChI
[show]
Properties
Molecularformula
C14H6N2O8
Molarmass
330.21gmol−1
Density
1.963g/cm3
Hazards
Flashpoint
569.8°C
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Exceptwherenotedotherwise,dataaregivenformaterialsintheirstandardstate(at25°C,100kPa)
Infoboxreferences
Pyrroloquinolinequinone(PQQ)wasdiscoveredbyJ.G.Haugeasthethirdredoxcofactorafternicotinamideandflavininbacteria(althoughtheyhypothesisedthatitwasnaphthoquinone).[1]AnthonyandZatmanalsofoundtheunknownredoxcofactorinalcoholdehydrogenaseandnameditmethoxatin.[2]In1979,Salisburyandcolleagues[3]aswellasDuineandcolleagues[4]extractedthisprostheticgroupfrommethanoldehydrogenaseofmethylotrophsandidentifieditsmolecularstructure.AdachiandcolleaguesidentifiedthatPQQwasalsofoundinAcetobacter.[5]
TheseenzymescontainingPQQarecalledquinoproteins.Glucosedehydrogenase,oneofthequinoproteins,isusedasaglucosesensor.Subsequently,PQQwasfoundtostimulategrowthinbacteria.[6]Inaddition,antioxidantandneuro-protectiveeffectswerealsofound.[7]
In1989,RuckerandcolleaguesreportedthatmicedeprivedofPQQshowedvariousabnormalities,anditwassuggestedthatPQQmayalsohaveanimportantnutritionalroleinothermammals.[8]In2003,itwasreportedthataminoadipatesemialdehydedehydrogenase(AASDH)mightalsousePQQasacofactor,suggestingapossibilitythatPQQisavitamininmammals.[9]RuckerandcolleaguesconcludedthatinsufficientinformationisavailablesofartostatethatPQQisavitaminformammals,althoughPQQmaybeanimportantbiologicalfactor.[10]
ItwasrecentlyshownthatPQQmaystimulategrowthofplants(cucumbersandtomatoes)inhydroponiccultureandmaybethecausativefactorinplantgrowthstimulationbyastrainofPseudomonasfluorescensbacterium.[11]
PQQasaprostheticgrouponglucosedehydrogenasehasbeenutilizedattheanodeinanenzymebasedfuelcell.[12]
Contents
[hide]
1Supplementationbenefits
1.1Antioxidantcapacityandroleinmitochondrialhealth
1.2Mitochondrialbiogenesis
1.2.1Activationofsignalingmolecules
1.3Neuroprotection
1.4Cognition
1.5Cardioprotection
1.6Supplementdosage
2References
[edit]Supplementationbenefits
PQQistakenasadietarysupplementtosupportmitochondrialhealthandcellularenergyproduction,andtoprotectthebodyfromoxidativestress.Mostnotably,PQQstimulatesthespontaneousgrowthofnewmitochondriainagingcells,andactivatesgenesthatgovernmitochondrialreproduction,protection,andrepair.
[edit]Antioxidantcapacityandroleinmitochondrialhealth
Mitochondriaaretheprimaryenginesofalmostallbioenergyproductioninthehumanbodyandareamongthemostvulnerablephysiologicalstructurestodestructionfromoxidativedamage.Scientistsnowrecognizemitochondrialdysfunctionasakeybiomarkerofaging.[13][14][15][16][17][18]RelativetocellularDNA,mitochondrialDNApossessesfewdefensesagainstfreeradicaldamage,andisdependentuponantioxidantsforprotection.[19][20]PQQ’spowerfulfreeradical–scavengingcapacityprovidesthemitochondriawithsuperiorantioxidantprotectionduetoitshighmolecularstabilityandtheroleitplaysinenergytransferdirectlywithinthemitochondria.Unlikeotherantioxidants,theexceptionalmolecularstabilityofPQQallowsittocarryoutthousandsofelectrontransferswithoutundergoingmolecularbreakdown[21]
PQQisespeciallyeffectiveinneutralizingsuperoxideandhydroxylradicals,[22][23]twoprominentcausesofmitochondrialdysfunction.
AccordingtoaUniversityofCaliforniaatDavisstudy,“PQQis30to5,000timesmoreefficientinsustainingredoxcycling(mitochondrialenergyproduction)...thanothercommon[antioxidantcompounds],e.g.AscorbicAcid(VitaminC).”[24]
[edit]Mitochondrialbiogenesis
In2010,researchersattheUniversityofCaliforniaatDavisreleasedapeer-reviewedpublicationshowingthatPQQ’scriticalroleingrowthanddevelopmentstemsfromitsuniqueabilitytoactivatecellsignalingpathwaysdirectlyinvolvedincellularenergymetabolism,development,andfunction.
Mostsignificantly,thestudydemonstratedthatPQQnotonlyprotectsmitochondriafromoxidativestress—itpromotesthespontaneousgenerationofnewmitochondriawithinagingcells,aprocessknownasmitochondrialbiogenesis.[25]Theimplicationsofthisrevelationforhumanhealthandlongevityaresignificantbecausetheonlyotherknownmethodsproventostimulatemitochondiralbiogenesisinaginghumansareintenseaerobicexercise,[26]strictcaloricrestriction,[27]andcertainmedicationssuchasthiazolidinediones[28]andthediabetesdrugmetformin.[29]
[edit]Activationofsignalingmolecules
TheteamofresearchersattheUniversityofCaliforniaanalyzedPQQ’sinfluenceovercellsignalingpathwaysinvolvedinthegenerationofnewmitochondriaandfoundthattherearethreesignalingmoleculesactivatedbyPQQthatcausecellstoundergospontaneousmitochondrialbiogenesis:
[25]
PQQactivatesexpressionofPCG-1α(peroxisomeproliferator-activatedreceptorgammacoactivator1-alpha),a“masterregulator”thatmobilizescells’responsetovariousexternaltriggers.Itdirectlystimulatesgenesthatenhancemitochondrialandcellularrespiration,growth,andreproduction.Itscapacitytoupregulatecellularmetabolismatthegeneticlevelfavorablyaffectsbloodpressure,cholesterolandtriglyceridebreakdown,andtheonsetofobesity.[30]
PQQtriggerstheCREBsignalingprotein(cAMP-responseelement-bindingprotein),whichplaysapivotalroleinembryonicdevelopmentandgrowth.Italsobeneficiallyinteractswithhistones,molecularcompoundsshowntoprotectandrepaircellularDNA.[31]CREBalsostimulatesthegrowthofnewmitochondria.
PQQregulatesarecentlydiscoveredcellsignalingproteincalledDJ-1.AswithPCG-1αandCREB,DJ-1isintrinsicallyinvolvedincellfunctionandsurvival,hasbeenshowntopreventcelldeathbycombatingintensiveantioxidantstress,[32][33]andisofparticularimportancetobrainhealthandfunction.DJ-1damageandmutationhavebeenconclusivelylinkedtotheonsetofParkinson’sdiseaseandotherneurologicaldisorders.
[edit]Neuroprotection
PQQisapotentneuroprotectivenutrientthathasbeenshowntoprotectmemoryandcognitioninbothaginganimalsandhumans.[34][35]Ithasbeenshowntoreversecognitiveimpairmentcausedbychronicoxidativestressinpre-clinicalmodelsandimproveperformanceonmemorytests.[36]PQQsupplementationstimulatestheproductionandreleaseofnervegrowthfactorincellsthatsupportneuronsinthebrain,[37]apossibleexplanationforthemarkedimprovementofmemoryfunctionitproducesinaginghumansandrats.
PQQhasalsobeenshowntosafeguardagainsttheself-oxidationoftheDJ-1gene,anearlystepintheonsetofParkinson’sdisease.[38]
PQQprotectsbraincellsagainstoxidativedamagefollowingischemia-reperfusioninjury—theinflammationandoxidativedamagethatresultfromthesuddenreturnofbloodandnutrientstotissuesdeprivedofthembystroke.[39]Reactivenitrogenspecies(RNS)arisespontaneouslyfollowingstrokeandspinalcordinjuriesandimposeseverestressesondamagedneurons,producingasignificantproportionofsubsequentlong-termneurologicaldamage.[40]PQQsuppressesRNSinexperimentallyinducedstrokes,[41]andprovidesadditionalprotectionfollowingspinalcordinjurybyblockinginduciblenitricoxidesynthase(iNOS),amajorsourceofRNS.[42]
Inanimalmodels,administrationofPQQimmediatelypriortoinductionofstrokesignificantlyreducesthesizeofthedamagedbrainarea.[43]TheseobservationshavebeenextendedinvivobyshowingthatPQQprotectsagainstthelikelihoodofseverestrokeinanexperimentalanimalmodelforstrokeandbrainhypoxia.[39]
PQQinteractsbeneficiallywiththebrain’sneurotransmittersystems.ItprotectsneuronsbymodifyingtheN-methyl-D-aspartate(NMDA)receptor.[44][45]andinhibitingexcitotoxicity—thedamagingconsequenceoflong-termoverstimulationofneuronsthatisassociatedwithmanyneurodegenerativediseasesandseizures.[46][47][48][49]
PQQalsoprotectsthebrainagainstneurotoxicityinducedbyotherpowerfultoxins,includingmercury[50](asuspectedfactorinthedevelopmentofAlzheimer’sdisease[51])andoxidopamine[22](apotentneurotoxinusedbyscientiststoinduceParkinsonisminlaboratoryanimalsbydestroyingdopaminergicandnoradrenergicneurons.[52])
PQQpreventsaggregationofalpha-synuclein,aproteinassociatedwithParkinson’sdisease.[53]PQQalsoprotectsnervecellsfromtheoxidizingravagesoftheamyloid-betaproteinlinkedwithAlzheimer’sdisease,[54]andworkspreventativelytoblocknewamyloidbetamolecularstructuresfromformingbeforetheycancauseanydamage.[55]
[edit]Cognition
PQQhasbeenshowntopromotememory,attention,andcognitioninanimals[34]andhumans.
Inadouble-blind,placebo-controlledclinicaltrialconductedinJapanin2007,supplementationwith20mgperdayofPQQresultedinimprovementsontestsofhighercognitivefunctioninagroupof71middle-agedandelderlypeopleagedbetween40-70,whooutperformedtheplacebogroupbymorethantwofoldintheirstandardizedmemorytests.[35]
Interestingly,theresultsofthestudyalsosuggestasynergisticrelationshipbetweenPQQandthenutrientc
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