现代营养学之自由基疾病

自由基与疾病1精选课件MainContentWhatAreFreeRadicalsGenerationofFreeRadicalsinvitroTypesofFreeRadicalsDamageofROStoBiologicalMoleculesFreeRadicalsandDiseasesDefenseagainstROSAntioxidants2精选课件1WhatAreFreeRadicalsAnymolecule,atom,ion,group,containingoneormoreunpairedelectrons(不成对电子)intheoutmostshell(最外层)3精选课件FreeRadicalROS4精选课件CharacteristicsofFreeRadicalsHighreactivityTendtograborloseaelectron,formingastablestate.shortlifespan(lowconcentration)At37℃,freeradicalshaveshorthalflife(withexceptions):1O2,O2·-,RO·10-6s·OH10-9sR·10-8sROO·10-2sNO·6~50s过氧化叔丁基9500year10-6s10-9s10-8s6-50s5精选课件2GenerationofFreeRadicalsinvitro2.1Heating(Thermolysis热解)Frying(200℃)Oilmoleculesbreakintofreeradicalswhenthetemperatureisabove50℃friedfood→freeradical;cooking→lungcancerToastingToastedbreadandsteamedbreadcaramelizedsugar(焦糖)6精选课件2.2Electromagneticradiation(UV,X-ray,γ-ray)tyrosine(酪氨酸)inmilkmelanin(黑色素)andcarotene(胡萝卜素)intheskinporphyrin(卟啉)inthebloodgeneratefreeradicalunderradiation.7精选课件hvhvT:Biomacromolecules8精选课件2.3RedoxreactionFentonreaction9精选课件2.4Chemicalreactionoffreeradical

GrabHA·+RH→AH+R·

ElectrontransferX·－+Y→X+Y·－

AdditionreactionX·+RCH＝CHR→XRCH－CHR·10精选课件3TypesofFreeRadicals3.1Reactiveoxygenspecies(ROS)活性氧electrontransportchainproduceO2·－

O2+e→O2·－(超氧阴离子自由基)O2·－+2H++e→H2O2H2O2+H++e→H2O+HO·(羟自由基)HO·+H++e→H2OO2·－weakoxidantH2O2strongoxidantHO·verystrongoxidant11精选课件3.2Reactivenitrogenspecies(RNS)活性氮·NOImportantmessengerinsignaltransduction:N:O:.....Unpairedelectron·NO+O·2－→ONOO·－过氧亚硝基阴离子·NO+O2→NO2·12精选课件3.3Reactivehalogenspecies(RHS)活性卤HOClHOBrStrongoxidizingpropertyH2O2+Cl-→HOCl+HO-HOCl+RNH2→RNHCl+H2OPhagocyte噬菌细胞useRHStodestroyforeignmatters13精选课件4DamageofROStoBiologicalMoleculesFat,especiallyPUFAR··+RHCH3OOHCH3OOHMDA,丙二醛OO14精选课件ProteinROSbreakdowncrosslinkingHydrolysisCleaveatα-Carbon15精选课件CarbohydrateOHOHOHHOHOHHHOHOHOHOHOHHHOHOO2OHOOHHOHOHHHOHOO·+H2O2CrosslinkingwithDNA,RNAandprotein16精选课件OHOHOHOHHHOHOα-羰基醛17精选课件DNAROS18精选课件5FreeRadicalsandDiseases5.1FreeradicalsandcancerCarcinogenandcancerpromoterNADPH黄素蛋白P450CC·CC·C:Carcinogenorcancerpromoter19精选课件MetalExcessmeatHighFeinbloodFreeradicalROSDNAdamageActivateproto-oncogene20精选课件InflammationinflammationwhitecellsexcreteROSROSDNAdamageActivateproto-oncogene21精选课件5.2FreeRadicalsandagingWhatcausesaging?DenhamHarman,Aging:ATheoryBasedonFreeRadicalandRadiationChemistry.J.Gerontol.11,298-300(1956).22精选课件ROSandagingHighROS,shortlifespan23精选课件IncreasedoxidationstressDecreasedresistancetooxidationAging24精选课件ROScause:Mitochondrion(线粒体)mtDNAlossApproachtoROSLackofprotectionNoabilitytorepairAccelerateshorteningofchromosometelomere端粒25精选课件5.3FreeRadicalandVirusInfectionVirusinfectionActivatemonocyteandmacrophageROS/RNSComplexⅡPeroxideActivateNF-κBIFNTNFIL-1AcceleratevirusproliferationCellapoptosis26精选课件5.4FreeRadicalandObesityObesityleadsto:1)oxidationstressO2·－(blood),MDA(blood,kidneyandLDL),异前列烷(Urine)↗2)nitrationstressDecreaseproductionandbioavailabilityofNOIncreaseendothelialnitricoxidesynthase(eNOS)ONOO·－↗attackprotein27精选课件Visceral内脏fatInflammatorycytokineMildinflammationFreeradicalLipidperoxideAtherosclerosisObesityandAtherosclerosis28精选课件Obesity肾上腺素↗血管紧张素↗O2·－高血压动脉粥样硬化ObesityandHypertension29精选课件肥胖和胰岛素抵抗游离脂肪酸↗胰腺β细胞中UCP-2表达↗线粒体偶联↘ATP/ADP↘胰岛素分泌↘Ⅱ型糖尿病ROS↘对抗氧化应激ObesityandDiabetes30精选课件5.5FreeRadicalandGerontalDisease(老年病)Alzheimer’sdisease老年痴呆Parkinson’sdisease帕金森症Cataract白内障Skinaging皮肤老化31精选课件6DefenseAgainstROSElectrontransportchain0.2%O2→O2·－ROS32精选课件6.1Defensesysteminmitochondrion1)CytochromecCytc-Fe3++O2·－

→Cytc-Fe2++O2

Cytc-Fe2++H2O2→Cytc-Fe3++H2OEliminateHO·2)CoQQ+H+QH233精选课件6.2Antioxidantenzyme1)SuperoxideDismutaseO2·－H2O2SODWithoutSOD,reactionrate=5×105(L·mol-1·s-1)WithSOD,reactionrate=1.6×109(L·mol-1·s-1)104倍34精选课件2)CatalaseH2O2H2OCatalaseO2+Existinperoxisomesofallthecells35精选课件3)Glutathioneperoxidase(GPorGSHPeroxidase)ROOH+2GSH→ROH+H2O+GSSGH2O2+2GSH→2H2O+GSSGGSHPeroxidase36精选课件4)Glutathionereductase(GRorGSHReductase)GSSG+NADPH+H+→2GSH+NADP+GSHReductase37精选课件5)Glucose-6-phosphatedehydrogenase(G-6-PDH,葡萄糖-6-磷酸脱氢酶)葡萄糖-6-磷酸盐+NADP+→6-磷酸葡萄糖酸+NADPH+H+

G6PDH38精选课件39精选课件7AntioxidantAntioxidantsaresubstancesthatmayprotectyourcellsagainsttheeffectsoffreeradicals.Scavengingfreeradicals40精选课件7.1Antioxidantsinourbody7.1.1Watersolubleantioxidant：VCUricacid尿酸CompoundswithSH41精选课件VC40-140μmol/LinhumanbloodCannotbesynthesizedbyourbodyScavengingO2·－,HO·,andR·42精选课件Uricacid尿酸120-450μmol/Linhumanurine10timeshigherthanothermammalsBindingwithFe2+andCu2+Fe2+,Cu2+Fentonreaction,HO·UricacidBinding43精选课件Uricacid尿酸EliminatingHClOand1O2ScavengingHO·44精选课件CompoundswithSHGSH谷胱甘肽Lipoicacid硫辛酸CoenzymeA辅酶ACysteine半胱氨酸45精选课件7.1.2fat-soluble:VEBilirubin胆红素Carotenoid类胡萝卜素Cholesterol胆固醇Melatonin褪黑素Lipoicacid硫辛酸46精选课件VE47精选课件Bilirubin胆红素Mostpowerfulantioxidantinhumanserum.EliminatingROO·48精选课件Ca