1-维生素D的代谢及调控研究新进展

··2015JQ83052012KCT-29SLGQD13-19*[e-mail]*D723000Ｒ977.2A1006-7108201510-1267-06Dprohormone。D、、、、。DD。DD。DAdvanceinvitaminDmetabolismanditsregulatorymechanismQIShanshanWANGYongjiInstituteofvitaminDShaanxiUniversityofTechnologyShaanx[e-mail]linicalapplicationofvitaminDaprohormoneresultinsuccessfultreatmentforricketsandosteomalacia．ThemajorbiologicalfunctionofvitaminDistoregulatethemetabolismofcalciumandphosphateandboneformation．VitaminDinhibitscellproliferationandregulatesimmunesystemanditiseffectiveinthepreventionandtreatmentofmanydiseasessuchasosteoporosishyperparathyroidismpsoriasisautoimmunediseaseandcancer．ThereforethereisagreatexpectationongaininghealthybenefitsfromvitaminDsupplements．HoweveroverdosingvitaminDmaycauseseveresideeffects．ThisreviewdiscussestheeffectofthevitaminDhormonesystemanditsselfprotectionfunctionfromaspectsofmetabolismandregulationmechanismofvitaminD．KeywordsVitaminDMetabolismFunctionSideeffectsＲegulationmechanismD。D。D。12。D。DDprohormone。D、DD。1DDD。D。。76212015102110ChinJOsteoporosOctober2015Vol21No．10Publishedonline．wanfangdate．com．cndoi10.3969/j．issn．1006-7108.2015.10.024。1919EdwardMellanbyD。A3。1922McCollum“D”4。1919Huldshinsky56。SteenbockBlack7、HessWeinstock8、D。HolickD9。D。1971DeLucaD———125OH2D3、10。D125OH2D3。。DD、。D7-D。2DD。7-D3。D11。DD。25-25-D25-OHD。6P450cytochromeP450CYP27A1。CYP2Ｒ112。25-OHDDD。25-OHD20ng/mLdeficiency21～29ng/mLinsufficiency3030ng/mLsufficiency40～60ng/mL100ng/mL1。D25-OHD3DvitaminDbindingproteinDBP。25-OHDlα-1α-hydroxylase1125-D125OH2D13。125OH2DD1、。125OH2DDvitaminDreceptorVDＲ。VDＲ、、、、、β、、、、T、。VDＲ、、14-16。25-OHD3125OH2D324-2425D2425OH2D3、。19722425OH2D3DHolickDeLuca24-17125OH2D325-OH-D3。125OH2D3VDＲ24-18。DCYP24A124-19。24125OH2D3D3-23calcitroicacid2021D3-2322。3DD86212015102110ChinJOsteoporosOctober2015Vol21No．101DFig．1ChartofVitaminDmetabolismcalciumandphosphateabsorptioncalciumre-absorptioncalciummobilization。D。D。D、。parathyroidhormonePTHPTH124PTH125OH2D3125OH2D3。。1114。D。D。Dproliferation、differentiationapoptosis142324D125OH2D3、、、。125OH2D3。DI2526125OH2D3125OH2D327。125OH2D3、、、Ⅰ。D。510000IUD328。610000IUD329。1850000IUD23000IU630。D、31。D。DD32。96212015102110ChinJOsteoporosOctober2015Vol21No．104DDD。D325-OHD325-OHD2。125OH2D33。1α-125OH2D125OH2DPTH3423fibroblastgrowthfactor23FGF2335362。PTH1α-25-OHD125OH2D125OH2D3PTH125OH2D。125OH2DPTH125OH2D37。FGF23125OH2D125OH2DFGF23FGF23125OH2D35。。125OH2DVDＲ1α-24-24-hydroxylase。125OH2D/25OHD125OH2D38。125OH2DVDＲ/PTH1α-125OH2D。125OH2D。D。39125OH2D3125OH2D31α-。125OH2D3125OH2D3125OH2D3。“125OH2D3”“”VDＲ1α-。D。125OH2D3。2DFig．2TheregulationofvitaminDhormonemetabolism07212015102110ChinJOsteoporosOctober2015Vol21No．105D/D。D25-OHD25-OHDD。D。D。D125-OH2DPTH、FGF23“VDＲ”D。D。【】1Hossein-nezhadAHolickMF．VitaminDforhealthaglobalperspective．MayoClinProc2013887720-755．2HolickMFBinkleyNCBischoff-FerrariHAetal．EvaluationtreatmentandpreventionofvitaminDdeficiencyanendocrinesocietyclinicalpracticeguideline．JClinEndocrMetab2011961911-1930．3MellanbyE．Anexperimentalinvestigationonrickets．Lancet19191407-412．4McCollumEVSimmondsNBeckerJEetal．Anexperimentaldemonstrationoftheexistenceofavitaminwhichpromotescalciumdeposition．JBiolChem192253293-298．5McCollumEVSimmonsNPitzW．Therelationoftheunidentifieddietaryfactorsthefat-solubleAandwatersolubleBofthediettothegrowthpromotingpropertiesofmilk．JBiolChem19162733-38．6HuldshinskyK．Heilungvonrachitisdurchkunstlichhohensonne．DeutMedWochenschr191945712-713．7SteenbockH．Blackfat-solublevitamins．XVII．Theinductionofgrowth-promotingandcalcifyingpropertiesinarationbyexposuretoultravioletlight．JBiolChem192461405-422．8HessAFWeinstockM．Antirachiticpropertiesimpartedtolettuceandtogrowingwheatbyultravioletirradiation．ProcSocExpBiolMed1924225-6．9HolickMFMacLaughlinJAClarkMBetal．PhotosynthesisofprevitaminD3inhumanskinandthephysiologicconsequences．Sci1980210203-205．10DeLucaHFHolickMFSchnoesHKetal．Isolationandidentificationof125-dihydroxycholecalciferol．AmetaboliteofvitaminDactiveinintestine．Biochem1971102799-2804．11DeLucaHF．OverviewofgeneralphysiologicfeaturesandfunctionsofvitaminD．AmJClinNutr2004801689S-1696S．12ZhuJDeLucaHF．VitaminD25-hydroxylase-FourdecadesofsearchingarewethereyetArchBiochemBiophys201252330-36．13DeLucaHF．VitaminDthevitaminandthehormone．FedProc1974332211-2219．14WangYZhuJDeLucaHF．WhereisthevitaminDreceptorArchBiochemBiophys2012523123-133．15WangYBecklundBＲDeLucaHF．IdentificationofahighlyspecificandversatilevitaminDreceptorantibody．ArchBiochemBiophys2010494166-177．16WangYDeLucaHF．IsthevitaminDreceptorfoundinmuscleEndocrinol2011152354-363．17HolickMFSchnoesHKDeLucaHFetal．Isolationandidentificationof2425-dihydroxychoelcalciferolametaboliteofvitaminD3madeinthekidney．Biochem1972114151-4255．18TanakaYDeLucaHF．Stimulationof2425-dihydroxyvitaminD3productionby125-dihydroxyvitaminD3．Sci19741831198-1200．19ZieroldCDarwishHMDeLucaHF．Twovitaminresponseelementsfunctionintherat125-dihydroxyvitaminD24-hydroxylasepromoter．JBiolChem19952701675-1678．20BeckmanMJTadikonaPW