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1、,自由基与疾病,2,Main Content,What Are Free RadicalsGeneration of Free Radicals in vitroTypes of Free RadicalsDamage of ROS to Biological MoleculesFree Radicals and DiseasesDefense against ROSAntioxidants,3,1 What Are Free Radicals,Any molecule,atom,ion,group,containing one or more unpaired electrons(不成对电子
2、)in the outmost shell(最外层),4,5,Characteristics of Free Radicals,High reactivityTend to grab or lose a electron,forming a stable state.short lifespan(low concentration)At 37,free radicals have short half life(with exceptions):1O2,O2-,RO 10-6s OH 10-9s R 10-8s ROO 10-2s NO 650s 过氧化叔丁基 9500year,6,2 Gen
3、eration of Free Radicals in vitro,2.1 Heating(Thermolysis热解)Frying(200)Oil molecules break into free radicals when the temperature is above 50 fried food free radical;cooking lung cancerToastingToasted bread and steamed breadcaramelized sugar(焦糖),7,2.2 Electromagnetic radiation(UV,X-ray,-ray)tyrosin
4、e(酪氨酸)in milkmelanin(黑色素)and carotene(胡萝卜素)in the skinporphyrin(卟啉)in the bloodgenerate free radical under radiation.,8,9,2.3 Redox reactionFenton reaction,10,2.4 Chemical reaction of free radical Grab H A+RH AH+R Electron transfer X+Y X+Y Addition reaction X+RCHCHR XRCHCHR,11,3 Types of Free Radica
5、ls,3.1 Reactive oxygen species(ROS)活性氧 electron transport chain produce O2 O2+e O2(超氧阴离子自由基)O2+2H+e H2O2 H2O2+H+e H2O+HO(羟自由基)HO+H+e H2O O2 weak oxidant H2O2 strong oxidant HO very strong oxidant,12,3.2 Reactive nitrogen species(RNS)活性氮NOImportant messenger in signal transduction,NO+O2 ONOO 过氧亚硝基阴离子
6、NO+O2 NO2,13,3.3 Reactive halogen species(RHS)活性卤HOClHOBrStrong oxidizing propertyH2O2+Cl-HOCl+HO-HOCl+RNH2 RNHCl+H2OPhagocyte 噬菌细胞 use RHS to destroy foreign matters,14,4 Damage of ROS to Biological Molecules,Fat,especially PUFA,15,Protein,HydrolysisCleave at-Carbon,16,Carbohydrate,17,-羰基醛,18,DNA,R
7、OS,19,5 Free Radicals and Diseases,5.1 Free radicals and cancerCarcinogen and cancer promoter,NADPH,黄素蛋白,P450,C,C,C,C,C:Carcinogen or cancer promoter,20,Metal,21,Inflammation,22,5.2 Free Radicals and aging,What causes aging?Denham Harman,Aging:A Theory Based on Free Radical and Radiation Chemistry.J
8、.Gerontol.11,298-300(1956).,23,ROS and agingHigh ROS,short lifespan,24,Increased oxidation stressDecreased resistance to oxidation,Aging,25,ROS cause:Mitochondrion(线粒体)mtDNA lossApproach to ROSLack of protection No ability to repairAccelerate shortening of chromosome telomere端粒,26,5.3 Free Radical a
9、nd Virus Infection,Virus infection,27,5.4 Free Radical and Obesity,Obesity leads to:1)oxidation stressO2(blood),MDA(blood,kidney and LDL),异前列烷(Urine)2)nitration stressDecrease production and bioavailability of NOIncrease endothelial nitric oxide synthase(eNOS)ONOO attack protein,28,Visceral内脏 fat,In
10、flammatory cytokine,Mild inflammation,Free radical,Lipid peroxide,Atherosclerosis,Obesity and Atherosclerosis,29,Obesity,肾上腺素,血管紧张素,O2,高血压,动脉粥样硬化,Obesity and Hypertension,30,31,5.5 Free Radical and Gerontal Disease(老年病),Alzheimers disease 老年痴呆Parkinsons disease 帕金森症Cataract 白内障Skin aging 皮肤老化,32,6 D
11、efense Against ROS,Electron transport chain,33,6.1 Defense system in mitochondrion1)Cytochrome c Cyt c-Fe3+O2 Cyt c-Fe2+O2 Cyt c-Fe2+H2O2 Cyt c-Fe3+H2O Eliminate HO2)Co Q,Q+H+,QH2,34,6.2 Antioxidant enzyme1)Superoxide Dismutase,O2,H2O2,SOD,Without SOD,reaction rate=5105(Lmol-1s-1)With SOD,reaction r
12、ate=1.6109(Lmol-1s-1),35,2)Catalase,H2O2,H2O,Catalase,O2,+,Exist in peroxisomes of all the cells,36,3)Glutathione peroxidase(GP or GSH Peroxidase),ROOH+2GSH ROH+H2O+GSSGH2O2+2GSH 2H2O+GSSG,GSH Peroxidase,37,4)Glutathione reductase(GR or GSH Reductase),GSSG+NADPH+H+2GSH+NADP+,GSH Reductase,38,5)Gluco
13、se-6-phosphate dehydrogenase(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+,G6PDH,39,40,7 Antioxidant,Antioxidants are substances that may protect your cells against the effects of free radicals.Scavenging free radicals,41,7.1 Antioxidants in our body7.1.1 Water soluble antioxidant：VCUric aci
14、d 尿酸Compounds with SH,42,VC40-140 mol/L in human bloodCan not be synthesized by our bodyScavenging O2,HO,and R,43,Uric acid 尿酸120-450 mol/L in human urine10 times higher than other mammalsBinding with Fe2+and Cu2+,44,Uric acid 尿酸Eliminating HClO and 1O2Scavenging HO,45,Compounds with SHGSH 谷胱甘肽Lipoi
15、c acid 硫辛酸Coenzyme A 辅酶ACysteine 半胱氨酸,46,7.1.2 fat-soluble:VEBilirubin 胆红素Carotenoid 类胡萝卜素Cholesterol 胆固醇Melatonin 褪黑素Lipoic acid 硫辛酸,47,VE,48,Bilirubin 胆红素Most powerful antioxidant in human serum.Eliminating ROO,49,Carotenoid 类胡萝卜素Scavenging 1O2,ROO,50,Cholesterol 胆固醇Antioxidant in blood and tissue
16、sMelatonin 褪黑素Most suitable antioxidant for protecting DNA,51,7.1.3 金属络合物Binding with metals,preventing them from generating OH through Fenton reaction,52,7.2 Antioxidants in foodNatural plantFruits and vegetablesHerbsSynthesized chemicalsBHA,BHT,53,7.3 MineralsSeActive site of GSH Peroxidase克山病（缺硒）,SE,54,CuActive site of CuZnSOD 铜锌SOD and ceruloplasmin 铜蓝蛋白,ceruloplasmin,55,ZnActive Site of CuZnSOD，Control the synthesis of metallothionein 金属硫蛋白eliminating OH,56,自由基与经络,DCFH-DA染色绿色荧光,MitoSOX染色红色荧光,57,自由基与经络,脾、胃、肾、感知,58,THANK YOU!,
