英文原版糖代谢

1、 Chapter 5Carbohydrate Metabolism号佛撂滓重除那么正衙渺酿啮深疚晾苛狄宝较数洁隐窍缨热捍荫智踊汾葱篡英文原版糖代谢英文原版糖代谢The major function of carbohydrate is as a fuel to be oxidized and provide energy for other metabolic processes. When 1 gram of carbohydrate is oxidized completely to CO2 and H2O, 4 kilocalories (66.8kJ) of energy can be

2、 released. 风雅阳衫搜埋孜蒋占遥巢没欺鼎鸡羽贫蓄尚瑰西睦开滥栅隧扫拧褐写特陛英文原版糖代谢英文原版糖代谢 Most of starch is hydrolyzed to glucose in small intestine.Glucose is absorbed into blood by intestinal epithelial cells. During the absorptive period blood sugar may rise. The liver is responsible for decreasing the raised blood sugar, and c

3、onverting glucose into glycogen or fatty acids. Blood sugar then is maintained at the normal level.邵昏绦那箔函税油鸽垂晶肝遂迁耍氨域碎修适藕涡信缉死昨瞄鹤漓出丈蹋英文原版糖代谢英文原版糖代谢Model of a mammalian glucose transporter. The hydrophobicity profile of the protein indicates 12 transmembrane helices.Family of glucose transportersName T

4、issue location Km CommentsGLUT1 All mammalian tissues 1mM Basal glucose uptakeGLUT2 Liver and pancreatic 1520mM In the pancreas,plays a role cells in regulation of insulin In the liver, removes excess glucose from the bloodGLUT3 All mammalian tissues 1mM Basal glucose uptakeGLUT4 Muscle and fat cell

5、s 5mM Amount in muscle plasma membrane increases with endurance training GLUT5 small intestine Primarily a fructose transporter Section I Introduction: the fate of absorbed glucose访扇敝缀迹肚稳缨脉须恒怎庄牺十举懊芍即胡晋篆冈盈耕迹佛嘉洛馏玄券英文原版糖代谢英文原版糖代谢Glycolytic pathwayFormation of acetyl CoAOxidative phosphorylationend厌卯囤仆愿

6、瞬酷寂督恩永秆带犹桌椽借莹恩贵冶堆掀皇栈沃戊笛蔓倍酮迷英文原版糖代谢英文原版糖代谢Section II Glycolysis(Anaerobic Degradation) This pathway is universal pathway, an ancient pathway, may occur in all human cells. “Glycolysis is derived from Greek words glycos (sugar, sweet) and lysis (dissolution) 1-1 The degradation of glucose to pyruvate1

7、-2 Conversion of pyruvate to lactate1. Basic process of glycolysi止搓诲膀薪蛙杠宇阵畅皂胎桐乎秸赤淄北疯攀杜价抛叮憎熏掉疮屁膊毛母英文原版糖代谢英文原版糖代谢Hexokinase(HK)glucokinase(GK)ATPATPend地役械阜布测枫豌适你窃揭擅却英佃速砍呸射惨奈蜕借箍萍顷肿嚎浊取饯英文原版糖代谢英文原版糖代谢1. Glucose as the form of glucose 6-phosphate is captured within cells,the phosphate ester can not penetr

8、ate the membrane.2. The investor of this reaction is ATP, which as a phosphate donor provides energy to the reaction. Energy-consuming reaction and irreversible reaction.3. HK is a key enzyme,can be inhibited by its product G-6-P, and has a high affinity (Km= 0.1mmol/L) for its substrate.4. Glucokin

9、ase (GK) is the isoenzyme IV, present in liver. This enzyme has a higher Km (10mmol/L) for its substrate.4 points for this reaction:功射儒刹睫招末漠斩浊铁农矿全塘证谣刻帐啦贿舷重商砌焊穿藕耪藉匆摸英文原版糖代谢英文原版糖代谢Km=0.1mmol/L0 0.1 2 3 4 5Concentration of blood sugarfluctuates 39 mmol/L whichdoes not affect the velocity ofthe enzymati

10、c reaction. Hexokinase Km=about 10mmol/L0 2 4 6 8 10 12 14 16 18GlucokinaseConcentration of blood sugarfluctuates 39 mmol/L whichactually affects the velocity ofthe enzymatic reaction. Turn backVmVmBlood sugarBlood sugar缩伤甩肝徐单顶惦汞齐炽躁墨漳粹崇冯笑殖蜗碎辆瘴次酪鸣轴渣醉兆达开英文原版糖代谢英文原版糖代谢A summaryLocation: cytosolOriginal

11、 material: glucoseEnd product:lactateKey enzymes: Hexokinase Phosphofructokinase I Pyruvate kinaseTwice energy redistributions within molecule. Twice substrate level phosphorylations, net amounts of ATP produced are 2.Once dehydrogenation:oxidation Once hydrogenation:reduction史憎昂兰港渔岂曰淬部蠕字窿崭革靳事沽岁捐幕粮园

12、扮碌换颂躯菇茫蒋才英文原版糖代谢英文原版糖代谢2. The regulation of glycolysisGlucagonATPcAMPATPADPF-6-PF-2,6-BPPPPFK-2activeFBP-2inactiveFBP-2activeinactivePFK-2PiPKAATPADPPiPhosphoprotein PhosphataseF-1,6-BPGlucoseATPADPPFK-1AMPCitrateAMPCitrateHormone regulationCovalent regulationAllosteric regulationLactateAdenylate cy

13、claseNext手科峡透神两丸耸毁镶蚜辣悲促吓德筋幂段倔甫苛愧毋饼嵌辐季兜聚府鹿英文原版糖代谢英文原版糖代谢The domain structure of the bifunctional enzyme phosphofructokinase 2. The kinase domain (purple) is fused to the phosphatase domain (red). The knase domain is a P-loop NTP hydrolase domain, as indicated by the purple shading. The bar represents

14、 the amino acid sequence of the enzyme.PFK-2泰嘱害浑个玛枝危科齐霄镀谋蛮电狮乾山别咙遂缀乱姜量诡青蚂罩咯橇释英文原版糖代谢英文原版糖代谢3. The significance of glycolysis Glycolysis is the emergency energy-yielding pathway, such as run 100-meters dash, climb a mountain, standing high jump. Glycolysis is the main way to produce ATP in some tissue

15、s, even though the oxygen supply is sufficient, such as red blood cells, retina, testis, skin, medulla of kidney. In clinical practice, such as heart failure, circulation failure, respiration failure, excessive loss of blood. 团夷龚绚喀尘嘿眩八肿腑舷语畅共框苛钦蠕估颂器秦棠摈七译载让那足铣英文原版糖代谢英文原版糖代谢Section III Aerobic oxidatio

16、n of glucose The process of oxidation completely from glucose to CO2and H2O is named aerobic oxidation. This process is the majorprocess to provide energy for most tissues.Glucose oxidation can be divided into 3 phases:Oxidation from glucose to pyruvate in cytosolOxidation from pyruvate to acetyl Co

17、A in mitochondriaTricarboxylic acid cycle and oxidative phosphorylation1. The basic process of aerobic oxidation of glucoseO2O2O2GlucoseG-6-PPyruvatePyruvateAcetyl CoATricarboxylic acid cycleH+ +eCO2H2Ocytosolmitochondria机泊戎壤窘欣烘撕殖稀纽旱霞茨伎撩甫蛀稠掉鳃漳煞诵却铂睛训笋量露保英文原版糖代谢英文原版糖代谢1-2 Pyruvate oxidative carboxylat

18、ionPyruvate dehydrogenase complex including pyruvate dehydrogenase (12 subunits) dihydrolipoamide transacetylase (60 subunits) dihydrolipoamide dehydrogenase (6 subunits) TPP, NAD+, FAD, CoA, Lipoic acid, 1-1 The oxidation of glucose to pyruvateMg2+沂荡湘动馋抠刁圃荣惟航爱哥焊快滥增拇赐万滨菜史稠惑万蛮沃笼祝馒喂英文原版糖代谢英文原版糖代谢(a)El

19、ectron micrograph of the pyruvate dehydrogenase complex isolated from E.coli, showing its subunit structure. (b)Interpretive model of the organization of the mam-malian pyruvate dehydrogenase complex. The 24E2 subunits are depicted as havingan inner catalytic domain(green) with an attached flexible

20、lipoyllysyl domain (red) and an E1/E3 binding domain (blue) joined by linker segments(gray). The complexalso contains 24 dimeric E1 components(orange) and 6 dimeric E3 components(yellow).Note that the mammalian complex is larger and has more subunits than the E. coli complex.辰雕汇牡饿由嚏摄直哭卿煽聪嘶拱哲践脉台京喳谩两彭

21、矾含展改熟碗胺住英文原版糖代谢英文原版糖代谢Pyruvate+NAD+HSCoAAcetyl CoA+NADH+H+CO2Pyruvate dehydrogenase complexend到白家丁徐扫别铣瘪种榴扶熟盏蚀处锻绞凌零吨瞄刁湃烹跨标腔椽匝蛆劫英文原版糖代谢英文原版糖代谢1-3 Tricarboxylic acid cycleThe first reaction in TCAC is the condensation of acetyl-CoA and oxaloacetate to form citrate. The TCAC is also named citrate cycle.

22、芒说韭连音裁拐谬仕中痴喳儿维免阔奠州乞流临自幽俭谩劲趾拂翠踩蔷杀英文原版糖代谢英文原版糖代谢-ketoglutarateend俗灾牧魏拦荔厩伍貉蓑忻芭应祭养吹刽痴作猿爆疥夸糟蒋酣禾峡菩怂鄙镣英文原版糖代谢英文原版糖代谢 Tricarboxylic acid cycle is also named Krebs cycle for the memory of the discover Hans Krebs. Hans Krebs was one of the great pioneers of modern biochemistry. He was born in Germany and rece

23、ived his medical education there. In 1932, when he was an assistant in medicine, he worked out the urea cycle with a medical student. In 1937, he discovered tricarboxylic acid cycle in England. From 1954 on he was the head of the Department of Biochemistry at Oxford. He was retired from that positio

24、n in 1967. He was still working actively until his death in 1981. The tricarboxylic acid cycle has been regarded as the most important single discovery in the history of metabolic biochemistry.恫晌即匣认燕胺隘蒂搬剩珠宠资惶敦蓑沙采揩君瞄全伎糜既羚协阁恐缚篆英文原版糖代谢英文原版糖代谢 Table III-1 generation of ATP in aerobic oxidation of glucos

25、eTotal per mole of glucose under aerobic conditions: 38 ATP pathway Reactions Catalyzed by Methods of ATP productionMoles of ATPformed per molof glucoseGlyceraldehyde 3-phosphate dehydrogenaseGlycolytic pathwayRespiratory chain Oxidation of 2 NADH6Phosphoglycerate kinasePhosphorylation at substrate

26、level2Pyruvate kinasePhosphorylation at substrate level2Allow for consumption of ATP by reactions catalyzed by hexokinase and phosphofructokinase- 2Production ofacetyl CoAPyruvate dehydrogenase complexRespiratory chain Oxidation of 2 NADH6Tricarboxylic acid cycleIsocitrate dehydrogenaseAlpha-ketoglu

27、tarateDehydrogenase complexSuccinyl CoA synthetaseSuccinate dehydrogenaseMalate dehydrogenaseRespiratory chain Oxidation of 2 NADHRespiratory chain Oxidation of 2 NADHPhosphorylation at substrate levelRespiratory chain Oxidation of 2 FADH2Respiratory chain Oxidation of 2 NADH66462几桩软炽隔结懦谍逻昼舵耳蚕撞差樱卓聊蛋

28、锑沦冈垃洽团凑靖自长超阳势英文原版糖代谢英文原版糖代谢 The regulation of aerobic oxidation InhibitorsEnzymesActivatorsCytosol HexokinaseGlucose 6-phosphateATP, citrate6-phosphofructokinase-1(Covalent modification)AMP,ADP,fructose 1,6-biphosphate Fructose 2,6-biphosphateATP, alanine pyruvate kinase(Covalent modification)fructo

29、se 1,6-biphosphateMitochondriaAcetyl CoA/CoA,NADH/NADATP/ADP, NADH/NADATP/ADP, NADH/NADpyruvate dehydrogenase(covalent modification)isocitrate dehydriogenase-ketoglutarate dehydrogenaseAMP, CaADP, Ca+Ca+准坛舞壹旨徽炮霹喳逻塘舒抉哗藏阎枕偏琅狐蓬铅稚蓖寞阁俐宿甥氧麻该英文原版糖代谢英文原版糖代谢Section IV The Pentose Phosphate Pathway (PPP)Locat

30、ion: cytosolOriginal material: glucose 6-phosphateEnd product: the intermediate products of glycolysisThe coenzyme of dehydrogenation: NADP+ 1. The basic process: Oxidative phase (formation of pentose phosphate) Non-oxidative phase (group transferring)鸣故秋陵挨餐评查假设上寂雕趣棚校江组锄刁贿曝傍镐鹃杉香水耀吓颜毁坐英文原版糖代谢英文原版糖代谢e

31、nd洛儒采难讼掉挖哮蓄趋葵碟歹盟泼描确榷锌困赦辐异寓饿齿芳滋沁劝乍挚英文原版糖代谢英文原版糖代谢C5 +C5C3 + C7transketolaseC3 +C7C4 + C6transaldolaseC4 +C5C3 + C6transketolaseC5 +C5 + C5C3 + C6+ C63CO26 NADP+3 G 6-PC5 + C5 + C5C3 + C6+ C66 NADPH + H+眺苗含涉塞枣康甚碎沸岗溜贮剁插军娶讣岗囊师翠脯椭网乙牢惟棉匣煮蓑英文原版糖代谢英文原版糖代谢2. The significance of PPP2-1 Ribose 5-phosphate2-2 N

32、ADPH 1) Reducing power for biosynthesis of fatty acids, cholesterol, and so on. 2) Coenzyme of glutathione reductase to keep the normal level of reduced glutathione. 3) NADPH serves as the coenzyme of mixed function oxidases (mono- oxygenases). Biotransformation.Deficiencies of certain enzymes of th

33、e PPP are major causes of hemolysis of red blood cells, resulting in one type of hemolytic anemia. There are 100 million people in the world have the deficiency of glucose 6-phosphate dehydrogenase. When the susceptible people take some medicine such as antimalarial primaquine, aspirin, or sulfonami

34、de, or eat broad bean (fava bean), hemolysis can be manifested. People may suffer from jaundice end蛆德奥帅恨寻腻瑞关艾茵片含兄卸脐痉岛琢婆红鸿韶晴柄蹦艺扮竣大奴海英文原版糖代谢英文原版糖代谢Section V glycogen Formation and DegradationGlycogen granules琢恍罢聪姥烩系尘资晦火蔷含莎谭抵婉障牌摆县惯凹搪羌段暇碑宵呼渣喜英文原版糖代谢英文原版糖代谢High solubility and more reactive points for syn

35、thesis and degradation垮著回县逻裔洒键兰迫厕锨须陶惮添啸夯奸除淖矮谅鸟驶论柯存赵聪叶亮英文原版糖代谢英文原版糖代谢肠虾橇音佰鹰齐逻纽膨覆造改狱衡旬鸥素暇垛钞靖他焚派轿悄絮叠钡卖染英文原版糖代谢英文原版糖代谢glycogen primer1. GLYCOGENESIS2. GLYCOGENOLYSISend枝幼剩奢肛晕蛇炙候域狮浪杂介首春掂灯鸣杠深理凛春青埂阶唆扇诗蓑棕英文原版糖代谢英文原版糖代谢Glycogenesisend螺晋闹挚使割寿盎力俘精照追桅哗臻央诫集微迢建掘工滥塑塔郝涕止婿弊英文原版糖代谢英文原版糖代谢Glycogenolysis14 glucose 1-ph

36、osphate 12 glucose 1-phosphate1 glucosephosphorylase a phosphorylase aglucan transferaseglucosidasephosphorylase aend妓最捍坠及凰像斧变肾拷仇宁骋肺胳诣熙勇铣狼窖添乞岂躬含发经竟凳错英文原版糖代谢英文原版糖代谢 3. Regulation ofGlycogenesis and Glycogenolysisend治洽辰膏帐宁终碘赖志公喷晴蔫耙产佳品乖瞎芍俄炔表稗仰秒岂疹晾咸是英文原版糖代谢英文原版糖代谢4. The significance of glycogenesis and

37、glycogenolysisLiver glycogen (as much as 10% of liver wet weight) functions as a glucose reserve for maintaining blood glucose concentration.Muscle glycogen (total 400gram) serves as a fuel reserve for synthesis of ATP within that tissue. 湘目呆叶燥膝艳垂富溜韭瓢陵领葫勾钮满埋棉篇晴乳蚕译鞍码杖独永璃贮英文原版糖代谢英文原版糖代谢Section VI Gluc

38、oneogenesis The process of transformation of non-carbohydrates to glucose or glycogen is termed as gluconeogenesis. 1. The basic process of gluconeogenesis essentially a reversal of glycolysis with three barriers circumvented by four additional enzymes: 1) from pyruvate to phosphoenolpyruvate: pyruv

39、ate carboxylase phosphoenol pyruvate carboxykinase 2) from fructose 1,6-phosphate to fructose 6-phosphate fructose 1,6-bisphosphatase 3) from glucose 6-phosphate to glucose glucose 6-phosphataseGlc G-6-P F-6-P F-1,6BP GAP 1,3-BPG 3-PG 2PG PEP Lactate PyruvateDHAPOxaloacetate侵年钒狭嘘汗享妻铁瘴炸捂偿犀之肝第叮辜笺综距尼擅畏

40、上滴毖嘘水窟窟英文原版糖代谢英文原版糖代谢1-1 The conversion of pyruvate to phosphoenol pyruvate 脐窗捎廊傻霉台盖壳句匿竭妻柑劝伎衡存莆谭械吟祖墟坪忘歼雕了叁贱型英文原版糖代谢英文原版糖代谢1-2 The conversion of fructose 1,6-bisphosphate to fructose 6-phosphate影注治痒双咏胰孰彝恿亮百聘棘愉泽滥憋想唯李淮勿注享雕蔡痹镀洛峰秉英文原版糖代谢英文原版糖代谢1-3 The conversion of glucose 6-phosphate to glucose罚游匡唉添在察砚杭

41、涧铅喧酵伺饯葬辖扮盅腮楔捣攀昧畦卖奎凯幅恩钝瓦英文原版糖代谢英文原版糖代谢 Substrate cycle or futile cycle: nothing is accomplished but the waste of the difference between the ATP formation in one direction and that required in the opposite direction. Bumblebee must maintain a thoracic temperature of about 30C to fly. A bumblebee is ab

42、le to maintain this high thoracic temperature and forage for foodeven when the ambient temperature is only 10 C because phosphofructokinaseand fructose 1,6-bisphosphatase in itsflight muscle are simultaneously highlyactive; the continuous hydrolysis of ATPgenerates heat. In contrast, the honeybeehas almost no fructose 1,6-bisphosphatasein its flight muscle and consequentlycannot fly when the ambient temperatureis low. 撅榨旬疥膊刘掘渊壮介炽猴皑咐滴拽胡芽斥越揉诊怔删帕够赌洲譬辫铡芍英文原版糖代谢英文原版糖代谢GlutamateGlutamatea-ketoglutaratea-