现代营养学之自由基疾病ppt课件

1、自在基与疾病自在基与疾病Main ContentWhat Are Free RadicalsGeneration of Free Radicals in vitroTypes of Free RadicalsDamage of ROS to Biological MoleculesFree Radicals and DiseasesDefense against ROSAntioxidants1 What Are Free RadicalsvAny molecule, atom, ion, group, containing one or more unpaired electrons (不成

2、对电子) in the outmost shell (最外层)BABA :Free RadicalROSCharacteristics of Free RadicalsvHigh reactivityvTend to grab or lose a electron, forming a stable state. vshort lifespan (low concentration)vAt 37, free radicals have short half life (with exceptions):v 1O2, O2- , RO 10-6sv OH 10-9s v R 10-8s v RO

3、O 10-2s v NO 650sv 过氧化叔丁基 9500year10-6s10-9s10-8s6-50s2 Generation of Free Radicals in vitro2.1 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 su

4、gar (焦糖)2.2 Electromagnetic radiation (UV, X-ray, -ray)tyrosine (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. HOHOH2hveHTThvT: Biomacromolecules2.3 Redox reactionFenton reaction3222FeOHHOFeOH2.4 Chemical reaction of free

5、radical Grab H A + RH AH + R Electron transfer X + Y X + Y Addition reaction X + RCHCHR XRCHCHR3 Types of Free Radicals3.1 Reactive oxygen species (ROS) 活性氧 electron transport chain produce O2 O2 + e O2 (超氧阴离子自在基) O2 + 2H+ + e H2O2 H2O2 + H+ + e H2O + HO (羟自在基) HO + H+ + e H2O O2 weak oxidant H2O2 s

6、trong oxidant HO very strong oxidant3.2 Reactive nitrogen species (RNS) 活性氮NOImportant messenger in signal transduction: N : O :. . .Unpaired electronNO + O2 ONOO 过氧亚硝基阴离子NO + O2 NO23.3 Reactive halogen species (RHS) 活性卤HOClHOBrStrong oxidizing propertyH2O2 + Cl- HOCl + HO-HOCl + RNH2 RNHCl + H2OPha

7、gocyte 噬菌细胞 use RHS to destroy foreign matters4 Damage of ROS to Biological MoleculesFat, especially PUFAR+RHCH3OOHCH3OOHMDA, 丙二醛丙二醛OOProteinROSbreakdowncrosslinkingHydrolysisCleave at -CarbonCarbohydrateOHOHOHHOHOHHHOHOHOHOHOHHHOHOO2OHOOHHOHOHHHOHOO+H2O2Crosslinking with DNA, RNA and proteinOHOHOHO

8、HHHOHO-羰基醛羰基醛DNAROS5 Free Radicals and Diseases5.1 Free radicals and cancerCarcinogen and cancer promoterNADPH黄素蛋白黄素蛋白P450CCCCC: Carcinogen or cancer promoterMetalExcess meatHigh Fe in blood3222FeOHHOFeOHFree radicalROSDNA damageActivate proto-oncogeneInflammationinflammationwhite cells excrete ROSR

9、OSDNA damageActivate proto-oncogene5.2 Free Radicals and agingvWhat causes aging?vDenham Harman, Aging: A Theory Based on Free Radical and Radiation Chemistry. J. Gerontol. 11, 298-300 (1956).ROS and agingHigh ROS, short lifespanIncreased oxidation stressDecreased resistance to oxidation ROS cause:M

10、itochondrion (线粒体) mtDNA lossApproach to ROSLack of protection No ability to repairAccelerate shortening of chromosome telomere端粒5.3 Free Radical and Virus InfectionVirus infectionActivate monocyte and macrophageROS/RNSComplex PeroxideActivate NF-BIFNTNFIL-1Accelerate virus proliferationCell apoptos

11、is5.4 Free Radical and ObesityObesity 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 proteinVisceral内脏内脏 fatInflammatory cytokineMild infla

12、mmationFree radicalLipid peroxideAtherosclerosisObesity and AtherosclerosisObesity肾上腺素肾上腺素 血管紧张素血管紧张素 O2高血压高血压动脉粥样硬化动脉粥样硬化Obesity and Hypertension肥胖和胰岛素抵抗肥胖和胰岛素抵抗游离脂肪酸游离脂肪酸 胰腺胰腺细胞中细胞中UCP-2表达表达 线粒体偶联线粒体偶联 ATP/ADP 胰岛素分泌胰岛素分泌 型糖尿病型糖尿病ROS 对抗氧化应激对抗氧化应激Obesity and Diabetes5.5 Free Radical and Gerontal Dis

13、ease (老年病)vAlzheimers disease 老年痴呆老年痴呆vParkinsons disease 帕金森症帕金森症vCataract 白内障白内障vSkin aging 皮肤老化皮肤老化6 Defense Against ROSvElectron transport chain0.2%O2O2 ROS6.1 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 Q22OO

14、Q + H+QH26.2 Antioxidant enzyme1) Superoxide DismutaseO2H2O2SODWithout SOD, reaction rate=5105 (Lmol-1s-1)With SOD, reaction rate=1.6109 (Lmol-1s-1)104倍倍v2) CatalaseH2O2H2OCatalaseO2+Exist in peroxisomes of all the cellsv3) Glutathione peroxidase v(GP or GSH Peroxidase )ROOH + 2GSH ROH + H2O + GSSGH

15、2O2 + 2GSH 2H2O + GSSGGSH Peroxidasev4) Glutathione reductase v(GR or GSH Reductase )GSSG + NADPH + H+ 2GSH + NADP+GSH Reductasev5) Glucose-6-phosphate dehydrogenasev(G-6-PDH, 葡萄糖-6-磷酸脱氢酶)葡萄糖葡萄糖-6-磷酸盐磷酸盐 + NADP+ 6-磷酸葡萄糖酸磷酸葡萄糖酸 + NADPH + H+ G6PDH7 AntioxidantvAntioxidants are substances that may prot

16、ect your cells against the effects of free radicals.vScavenging free radicalsv7.1 Antioxidants in our bodyv7.1.1 Water soluble antioxidant：vVCvUric acid 尿酸vCompounds with SHvVCv40-140 mol/L in human bloodvCan not be synthesized by our bodyvScavenging O2, HO, and R AHOHHOAH2222AHOHHOAH22AHRHRAH2vUric

17、 acid 尿酸v120-450 mol/L in human urinev10 times higher than other mammalsvBinding with Fe2+ and Cu2+Fe2+, Cu2+Fenton reaction, HOUric acidBindingvUric acid 尿酸vEliminating HClO and 1O2vScavenging HOAHUAHUUOHHOU2vCompounds with SHvGSH 谷胱甘肽vLipoic acid 硫辛酸vCoenzyme A 辅酶AvCysteine 半胱氨酸HRSRRSHR2121v7.1.2

18、fat-soluble:vVEvBilirubin 胆红素vCarotenoid 类胡萝卜素vCholesterol 胆固醇vMelatonin 褪黑素vLipoic acid 硫辛酸vVENADVNADHVVVVVVROOHVROOCCCECEEEvBilirubin 胆红素vMost powerful antioxidant in human serum.vEliminating ROOvCarotenoid 类胡萝卜素vScavenging 1O2, ROOheatCARCARCAROCARO221ROOCARROOROOCARROOCARROOCARROOvCholesterol 胆固醇vAntioxidant in blood and tissuesvMelatonin 褪黑素vMost suitable antioxidant for protecting DNAv7.1.3 金属络合物vBinding with metals, preventing them from generating OH through Fenton reactionv7.2 Antioxidants in foodvNatural plantvFruits and vegetablesvHerbsvSynthesized chemicalsvBHA,