人类怎样改善“先天性”维生素C缺乏症

时间 : 2009-11-28 00:00:32 来源：www.91sqs.com

[摘要]

A new study appears to explain how humans, along with other higher primates, guinea pigs and fruit bats, get by with what some have called an inborn m

Anewstudyappearstoexplainhowhumans,alongwithotherhigherprimates,guineapigsandfruitbats,getbywithwhatsomehavecalledan"inbornmetabolicerror":aninabilitytoproducevitaminCfromglucose.

Unlikethemorethan4,000otherspeciesofmammalswhomanufacturevitaminC,andlotsofit,theredbloodcellsofthehandfulofvitaminC-defectivespeciesarespeciallyequippedtosuckupthevitamin'soxidizedform,so-calledL-dehydroascorbicacid（DHA）,theresearchersreportintheMarch21stissueofCell,apublicationofCellPress.Onceinsidethebloodcells,thatDHA--whichisimmediatelytransformedbackintoascorbicacid（a.k.a.vitaminC）--canbeefficientlycarriedthroughthebloodstreamtotherestofthebody,theresearcherssuggest.

"Evolutionisamazing.Eventhoughpeopletalkaboutthisasan'inbornerror'--ametabolicdefectthatallhumanshave--thereisalsothisincrediblemannerinwhichwe'verespondedtothedefect,usingsomeofthebody'smostplentifulcells,"saidNaomiTaylorofUniversitéMontpellierIandIIinFrance,notingthatthebodyharborsbillionsofredbloodcells."[Throughevolution],we'vecreatedthissystemthattakesouttheoxidizedformofvitaminCandtransportstheessential,antioxidantform."

Meanwhile,theredcellsofothermammalsapparentlytakeupverylittle,ifany,DHA,whichmightexplainwhytheyneedtoproducesomuchmorevitaminCthanweneedtogetfromourdiets,Taylorsaid.TherecommendeddailydoseofvitaminCforhumansisjustonemg/kg,whilegoats,forexample,producethevitaminatastrikingrateof200mg/kgeachday.

Inessence,theredcellsofanimalsthatcan'tmakevitaminCrecyclewhatlittlethey'vegot.Earlierstudieshaddescribedtherecyclingprocess,Taylorsaid."Ourcontributiontothewholestoryistoshowthatthisprocessofrecyclingexistsspecificallyinmammalsthatdon'tmakevitaminC."

ScientistsknewthattheproteincalledGlut1,foundinthemembranesofcellsthroughoutthebody,istheprimarytransporterofglucose.TheyalsoknewthatGlut1cantransportDHAtoo,thankstothestructuralsimilaritiesbetweenthetwomolecules.Inbiochemicalassays,itappearedthattheglucosetransporterwouldmoveglucoseandDHAinterchangeably.

But,inthenewstudy,Taylor'sgroupmadeasurprisingdiscovery:TheGlut1onhumanredbloodcellsstronglyfavorsDHAoverglucose.Infact,thehumanbloodcellsareknowntocarrymoreGlut1thananyothercelltype,harboringmorethan200,000moleculesonthesurfaceofeverycell.Nevertheless,theresearchersfound,asredbloodcellsdevelopinthebonemarrow,theirtransportofglucosedeclinesevenasGlut1numbersskyrocket.

ThekeytotheglucosetransportersswitchtoDHA,theyshow,isthepresenceofanothermembraneproteincalledstomatin.（Accordingly,inpatientswithararegeneticdisorderofredcellmembranepermeabilitywhereinstomatinisonlypresentatlowlevels,DHAtransportisdecreasedby50%whileglucoseuptakeissignificantlyincreased,theyreport.）

Then,anothersurprise:Theresearchersfoundthattheredcellsofmice,aspeciesthatcanproducevitaminC,don'tcarryGlut1ontheirredbloodcellsatall.TheycarryGlut4instead.TheysuspectedthatthedifferencesinhumanredbloodcellsmightbelinkedtoourinabilitytosynthesizethereducedformofDHA,vitaminC,fromglucose.Infact,theyconfirmedGlut1expressiononhuman,guineapigandfruitbatredbloodcells,butnotonanyothermammalianredcellstested,includingrabbit,rat,cat,dogandchinchilla.Next,theytookacloserlookatprimates.PrimatesbelongingtotheHaplorrhinisuborder（includingprosimiantarsiers,newworldmonkeys,oldworldmonkeys,humansandapes）havelosttheabilitytosynthesizevitaminC,whereasprimatesintheStrepsirrhinisuborder（includinglemurs）arereportedlyabletoproducethisvitamin,Taylorexplained.

Notably,theydetectedGlut1onalltestedredbloodcellsofprimateswithinthehigherprimategroup,includinglong-tailedmacaques,rhesusmonkeys,baboonsandmagotmonkeys.Inmarkedcontrast,Glut1wasnotdetectedonlemurredbloodcells.Moreover,theyreport,althoughDHAuptakeinhumanandmagotredcellswassimilar,theleveloftransportincellsfromthreedifferentlemurspecieswaslessthan10%ofthatdetectedinhigherprimates.

"Redbloodcell-specificGlut1expressionandDHAtransportarespecifictraitsofthefewvitaminC-deficientmammalianspecies,encompassingonlyhigherprimates,guineapigsandfruitbats,"theresearchersconcluded."Indeed,theredcellsofadultmicedonotharborGlut1anddonottransportDHA.Rather,Glut4isexpressedontheircells.Thus,theconcomitantinductionofGlut1andstomatinduringredbloodcelldifferentiationconstitutesacompensatorymechanisminmammalsthatareunabletosynthesizetheessentialascorbicacidmetabolite,"otherwiseknownasvitaminC.

TheresearchersincludeAmelieMontel-Hagen,InstitutdeGenetiqueMoleculairedeMontpellier,CNRS,Universite´MontpellierIandII,Montpellier,France;SandrinaKinet,InstitutdeGenetiqueMoleculairedeMontpellier,CNRS,Universite´MontpellierIandII,Montpellier,France;NicolasManel,InstitutdeGenetiqueMoleculairedeMontpellier,CNRS,Universite´MontpellierIandII,Montpellier,France;CedricMongellaz,InstitutdeGenetiqueMoleculairedeMontpellier,CNRS,Universite´MontpellierIandII,Montpellier,France;RainerProhaska,MaxF.PerutzLaboratories,DepartmentofMedicalBiochemistry,MedicalUniversityofVienna,Vienna,Austria;Jean-LucBattini,InstitutdeGenetiqueMoleculairedeMontpellier,CNRS,Universite´MontpellierIandII,Montpellier,France;JeanDelaunay,Hematologie,HopitaldeBicetre,APHP,INSERMU779,Faculte´deMedecineParis-Sud,LeKremlin-Bicetre,France;MarcSitbon,InstitutdeGenetiqueMoleculairedeMontpellier,CNRS,Universite´MontpellierIandII,Montpellier,France;andNaomiTaylor,InstitutdeGenetiqueMoleculairedeMontpellier,CNRS,Universite´MontpellierIandII,Montpellier,France.