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1、现代营养学之自由基疾病1自由基与疾病自由基与疾病现代营养学之自由基疾病2main contentwhat are free radicalsgeneration of free radicals in vitrotypes of free radicalsdamage of ros to biological moleculesfree radicals and diseasesdefense against rosantioxidants现代营养学之自由基疾病31 what are free radicalsvany molecule, atom, ion, group, containin
2、g one or more unpaired electrons (不成对电子不成对电子) in the outmost shell (最外最外层层)baba :现代营养学之自由基疾病4free radicalros现代营养学之自由基疾病5characteristics of free radicalsvhigh reactivitytend to grab or lose a electron, forming a stable state. vshort lifespan (low concentration)vat 37, free radicals have short half li
3、fe (with exceptions): 1o2, o2- , ro 10-6s oh 10-9s r 10-8s roo 10-2s no 650s 过氧化叔丁基过氧化叔丁基 9500year10-6s10-9s10-8s6-50s现代营养学之自由基疾病62 generation of free radicals in vitro2.1 heating (thermolysis热解热解)frying (200)oil molecules break into free radicals when the temperature is above 50 fried food free rad
4、ical; cooking lung cancertoastingtoasted bread and steamed breadcaramelized sugar (焦糖焦糖)现代营养学之自由基疾病72.2 electromagnetic radiation (uv, x-ray, -ray)tyrosine (酪氨酸酪氨酸) in milkmelanin (黑色素黑色素) and carotene (胡萝卜素胡萝卜素 ) in the skinporphyrin (卟啉卟啉) in the bloodgenerate free radical under radiation. 现代营养学之自
5、由基疾病8hohoh2hvehtthvt: biomacromolecules现代营养学之自由基疾病92.3 redox reactionfenton reaction3222feohhofeoh现代营养学之自由基疾病102.4 chemical reaction of free radical grab h a + rh ah + r electron transfer x + y x + y addition reaction x + rchchr xrchchr现代营养学之自由基疾病113 types of free radicals3.1 reactive oxygen species
6、 (ros) 活性氧 electron transport chain produce o2 o2 + e o2 (超氧阴离子自由基超氧阴离子自由基) o2 + 2h+ + e h2o2 h2o2 + h+ + e h2o + ho (羟自由基羟自由基) ho + h+ + e h2o o2 weak oxidant h2o2 strong oxidant ho very strong oxidant现代营养学之自由基疾病123.2 reactive nitrogen species (rns) 活性氮vnovimportant messenger in signal transduction
7、: n : o :. . .unpaired electronno + o2 onoo 过氧亚硝基阴离子过氧亚硝基阴离子no + o2 no2现代营养学之自由基疾病133.3 reactive halogen species (rhs) 活性卤vhoclvhobrvstrong oxidizing propertyvh2o2 + cl- hocl + ho-vhocl + rnh2 rnhcl + h2ovphagocyte 噬菌细胞噬菌细胞 use rhs to destroy foreign matters现代营养学之自由基疾病144 damage of ros to biological
8、 moleculesfat, especially pufar+rhch3oohch3oohmda, 丙二醛丙二醛oo现代营养学之自由基疾病15proteinrosbreakdowncrosslinkinghydrolysiscleave at -carbon现代营养学之自由基疾病16carbohydrateohohohhohohhhohohohohohhhohoo2ohoohhohohhhohoo+h2o2crosslinking with dna, rna and protein现代营养学之自由基疾病17ohohohohhhoho-羰基醛羰基醛现代营养学之自由基疾病18dnaros现代营养
9、学之自由基疾病195 free radicals and diseases5.1 free radicals and cancercarcinogen and cancer promoternadph黄素蛋白黄素蛋白p450ccccc: carcinogen or cancer promoter现代营养学之自由基疾病20metalexcess meathigh fe in blood3222feohhofeohfree radicalrosdna damageactivate proto-oncogene现代营养学之自由基疾病21inflammationinflammationwhite ce
10、lls excrete rosrosdna damageactivate proto-oncogene现代营养学之自由基疾病225.2 free radicals and agingvwhat causes aging?vdenham harman, aging: a theory based on free radical and radiation chemistry. j. gerontol. 11, 298-300 (1956).现代营养学之自由基疾病23ros and aginghigh ros, short lifespan现代营养学之自由基疾病24increased oxidat
11、ion stressdecreased resistance to oxidation 现代营养学之自由基疾病25ros cause:vmitochondrion (线粒体线粒体) mtdna lossapproach to roslack of protection no ability to repairvaccelerate shortening of chromosome telomere端粒端粒现代营养学之自由基疾病265.3 free radical and virus infectionvirus infectionactivate monocyte and macrophage
12、ros/rnscomplex peroxideactivate nf-bifntnfil-1accelerate virus proliferationcell apoptosis现代营养学之自由基疾病275.4 free radical and obesityobesity leads to:1) oxidation stresso2 (blood), mda (blood, kidney and ldl), 异前列烷异前列烷 (urine) 2) nitration stressdecrease production and bioavailability of noincrease en
13、dothelial nitric oxide synthase (enos) onoo attack protein现代营养学之自由基疾病28visceral内脏内脏 fatinflammatory cytokinemild inflammationfree radicallipid peroxideatherosclerosisobesity and atherosclerosis现代营养学之自由基疾病29obesity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现代营养学之自由基疾病30肥胖和胰岛素抵抗肥胖
14、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 diabetes现代营养学之自由基疾病315.5 free radical and gerontal disease (老年病老年病)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 皮肤老化皮肤老化现代营养学之自由基疾病326 defense against rosvele
15、ctron transport chain0.2%o2o2 ros现代营养学之自由基疾病336.1 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 q22ooq + h+qh2现代营养学之自由基疾病346.2 antioxidant enzyme1) superoxide dismutaseo2h2o2sodwithout sod, reaction rate=5105 (lmol-
16、1s-1)with sod, reaction rate=1.6109 (lmol-1s-1)104倍倍现代营养学之自由基疾病35v2) catalaseh2o2h2ocatalaseo2+exist in peroxisomes of all the cells现代营养学之自由基疾病36v3) glutathione peroxidase v(gp or gsh peroxidase )rooh + 2gsh roh + h2o + gssgh2o2 + 2gsh 2h2o + gssggsh peroxidase现代营养学之自由基疾病37v4) glutathione reductase
17、v(gr or gsh reductase )gssg + nadph + h+ 2gsh + nadp+gsh reductase现代营养学之自由基疾病38v5) 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+ g6pdh现代营养学之自由基疾病39现代营养学之自由基疾病407 antioxidantvantioxidants are substances that may protect your cells against
18、the effects of free radicals.vscavenging free radicals现代营养学之自由基疾病41v7.1 antioxidants in our bodyv7.1.1 water soluble antioxidant:vvcvuric acid 尿酸vcompounds with sh现代营养学之自由基疾病42vvcv40-140 mol/l in human bloodvcan not be synthesized by our bodyvscavenging o2, ho, and r ahohhoah2222ahohhoah22ahrhrah2现代
19、营养学之自由基疾病43vuric acid 尿酸v120-450 mol/l in human urinev10 times higher than other mammalsvbinding with fe2+ and cu2+fe2+, cu2+fenton reaction, houric acidbinding现代营养学之自由基疾病44vuric acid 尿酸veliminating hclo and 1o2vscavenging hoahuahuuohhou2现代营养学之自由基疾病45vcompounds with shvgsh 谷胱甘肽谷胱甘肽vlipoic acid 硫辛酸硫辛
20、酸vcoenzyme a 辅酶辅酶avcysteine 半胱氨酸半胱氨酸hrsrrshr2121现代营养学之自由基疾病46v7.1.2 fat-soluble:vvevbilirubin 胆红素胆红素vcarotenoid 类胡萝卜素类胡萝卜素vcholesterol 胆固醇胆固醇vmelatonin 褪黑素褪黑素vlipoic acid 硫辛酸硫辛酸现代营养学之自由基疾病47vvenadvnadhvvvvvvroohvrooccceceee现代营养学之自由基疾病48vbilirubin 胆红素vmost powerful antioxidant in human serum.veliminating roo现代营养学之自由基疾病49vcarotenoid 类胡萝卜素vscavenging 1o2, rooheatcarcarcarocaro221roocarrooroocarroocarroocarroo现代营养学之自由基疾病50vcholesterol 胆固醇胆固醇vantioxidant in blood an
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