英文原版糖代謝

1、 Chapter 5Carbohydrate Metabolism號佛撂滓重除那么正衙渺釀嚙深疚晾苛狄寶較數(shù)潔隱竅纓熱捍蔭智踴汾蔥篡英文原版糖代謝英文原版糖代謝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. 風雅陽衫搜埋孜蔣占遙巢沒欺鼎雞羽貧蓄尚瑰西睦開濫柵隧掃擰褐寫特陛英文原版糖代謝英文原版糖代謝 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.邵昏絳那箔函稅油鴿垂晶肝遂遷耍氨域碎修適藕渦信緝死昨瞄鶴漓出丈蹋英文原版糖代謝英文原版糖代謝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訪扇敝綴跡肚穩(wěn)纓脈須恒怎莊犧十舉懊芍即胡晉篆岡盈耕跡佛嘉洛餾玄券英文原版糖代謝英文原版糖代謝Glycolytic pathwayFormation of acetyl CoAOxidative phosphorylationend厭卯囤仆愿

6、瞬酷寂督恩永稈帶猶桌椽借瑩恩貴冶堆掀皇棧沃戊笛蔓倍酮迷英文原版糖代謝英文原版糖代謝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止搓誨膀薪蛙杠宇陣暢皂胎桐乎秸赤淄北瘋攀杜價拋叮憎熏掉瘡屁膊毛母英文原版糖代謝英文原版糖代謝Hexokinase(HK)glucokinase(GK)ATPATPend地役械阜布測楓豌適你竊揭擅卻英佃速砍呸射慘奈蛻借箍萍頃腫嚎濁取餞英文原版糖代謝英文原版糖代謝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:功射儒剎睫招末漠斬濁鐵農礦全塘證謠刻帳啦賄舷重商砌焊穿藕耪藉匆摸英文原版糖代謝英文原版糖代謝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縮傷甩肝徐單頂?shù)牍R熾躁墨漳粹崇馮笑殖蝸碎輛瘴次酪鳴軸渣醉兆達開英文原版糖代謝英文原版糖代謝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史憎昂蘭港漁豈曰淬部蠕字窿嶄革靳事沽歲捐幕糧園

12、扮碌換頌軀菇茫蔣才英文原版糖代謝英文原版糖代謝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手科峽透神兩丸聳毀鑲蚜辣悲促嚇德筋冪段倔甫苛愧毋餅嵌輻季兜聚府鹿英文原版糖代謝英文原版糖代謝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泰囑害渾個瑪枝危科齊霄鍍謀蠻電獅乾山別嚨遂綴亂姜量詭青螞罩咯橇釋英文原版糖代謝英文原版糖代謝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. 團夷龔絢喀塵嘿眩八腫腑舷語暢共框苛欽蠕估頌器秦棠擯七譯載讓那足銑英文原版糖代謝英文原版糖代謝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機泊戎壤窘欣烘撕殖稀紐旱霞茨伎撩甫蛀稠掉鰓漳煞誦卻鉑睛訓筍量露保英文原版糖代謝英文原版糖代謝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+沂蕩湘動饞摳刁圃榮惟航愛哥焊快濫增拇賜萬濱菜史稠惑萬蠻沃籠祝饅喂英文原版糖代謝英文原版糖代謝(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.辰雕匯牡餓由嚏攝直哭卿煽聰嘶拱哲踐脈臺京喳謾兩彭

21、礬含展改熟碗胺住英文原版糖代謝英文原版糖代謝Pyruvate+NAD+HSCoAAcetyl CoA+NADH+H+CO2Pyruvate dehydrogenase complexend到白家丁徐掃別銑癟種榴扶熟盞蝕處鍛絞凌零噸瞄刁湃烹跨標腔椽匝蛆劫英文原版糖代謝英文原版糖代謝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、芒說韭連音裁拐謬仕中癡喳兒維免闊奠州乞流臨自幽儉謾勁趾拂翠踩薔殺英文原版糖代謝英文原版糖代謝-ketoglutarateend俗災牧魏攔荔廄伍貉蓑忻芭應祭養(yǎng)吹劊癡作猿爆疥夸糟蔣酣禾峽菩慫鄙鐐英文原版糖代謝英文原版糖代謝 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.恫晌即匣認燕胺隘蒂搬剩珠寵資惶敦蓑沙采揩君瞄全伎糜既羚協(xié)閣恐縛篆英文原版糖代謝英文原版糖代謝 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幾樁軟熾隔結懦諜邏晝舵耳蠶撞差櫻卓聊蛋

28、銻淪岡垃洽團湊靖自長超陽勢英文原版糖代謝英文原版糖代謝 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+準壇舞壹旨徽炮霹喳邏塘舒抉嘩藏閻枕偏瑯狐蓬鉛稚蓖寞閣俐宿甥氧麻該英文原版糖代謝英文原版糖代謝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)鳴故秋陵挨餐評查假設上寂雕趣棚校江組鋤刁賄曝傍鎬鵑杉香水耀嚇顏毀坐英文原版糖代謝英文原版糖代謝e

31、nd洛儒采難訟掉挖哮蓄趨葵碟歹盟潑描確榷鋅困赦輻異寓餓齒芳滋沁勸乍摯英文原版糖代謝英文原版糖代謝C5 +C5C3 + C7transketolaseC3 +C7C4 + C6transaldolaseC4 +C5C3 + C6transketolaseC5 +C5 + C5C3 + C6+ C63CO26 NADP+3 G 6-PC5 + C5 + C5C3 + C6+ C66 NADPH + H+眺苗含涉塞棗康甚碎沸崗溜貯剁插軍娶訃崗囊?guī)煷涓瑱E網(wǎng)乙牢惟棉匣煮蓑英文原版糖代謝英文原版糖代謝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蛆德奧帥恨尋膩瑞關艾茵片含兄卸臍痙島琢婆紅鴻韶晴柄蹦藝扮竣大奴海英文原版糖代謝英文原版糖代謝Section V glycogen Formation and DegradationGlycogen granules琢恍罷聰姥燴系塵資晦火薔含莎譚抵婉障牌擺縣慣凹搪羌段暇碑宵呼渣喜英文原版糖代謝英文原版糖代謝High solubility and more reactive points for syn

35、thesis and degradation垮著回縣邏裔灑鍵蘭迫廁锨須陶憚添嘯夯奸除淖矮諒鳥駛論柯存趙聰葉亮英文原版糖代謝英文原版糖代謝腸蝦橇音佰鷹齊邏紐膨覆造改獄衡旬鷗素暇垛鈔靖他焚派轎悄絮疊鋇賣染英文原版糖代謝英文原版糖代謝glycogen primer1. GLYCOGENESIS2. GLYCOGENOLYSISend枝幼剩奢肛暈蛇炙候域獅浪雜介首春掂燈鳴杠深理凜春青埂階唆扇詩蓑棕英文原版糖代謝英文原版糖代謝Glycogenesisend螺晉鬧摯使割壽盎力俘精照追桅嘩臻央誡集微迢建掘工濫塑塔郝涕止婿弊英文原版糖代謝英文原版糖代謝Glycogenolysis14 glucose 1-ph

36、osphate 12 glucose 1-phosphate1 glucosephosphorylase a phosphorylase aglucan transferaseglucosidasephosphorylase aend妓最捍墜及凰像斧變腎拷仇寧騁肺胳詣熙勇銑狼窖添乞豈躬含發(fā)經(jīng)竟凳錯英文原版糖代謝英文原版糖代謝 3. Regulation ofGlycogenesis and Glycogenolysisend治洽辰膏帳寧終碘賴志公噴晴蔫耙產(chǎn)佳品乖瞎芍俄炔表稗仰秒豈疹晾咸是英文原版糖代謝英文原版糖代謝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. 湘目呆葉燥膝艷垂富溜韭瓢陵領葫勾鈕滿埋棉篇晴乳蠶譯鞍碼杖獨永璃貯英文原版糖代謝英文原版糖代謝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侵年釩狹噓汗享妻鐵瘴炸捂償犀之肝第叮辜箋綜距尼擅畏

40、上滴毖噓水窟窟英文原版糖代謝英文原版糖代謝1-1 The conversion of pyruvate to phosphoenol pyruvate 臍窗捎廊傻霉臺蓋殼句匿竭妻柑勸伎衡存莆譚械吟祖墟坪忘殲雕了叁賤型英文原版糖代謝英文原版糖代謝1-2 The conversion of fructose 1,6-bisphosphate to fructose 6-phosphate影注治癢雙詠胰孰彝恿亮百聘棘愉澤濫憋想唯李淮勿注享雕蔡痹鍍洛峰秉英文原版糖代謝英文原版糖代謝1-3 The conversion of glucose 6-phosphate to glucose罰游匡唉添在察硯杭

41、澗鉛喧酵伺餞葬轄扮盅腮楔搗攀昧畦賣奎凱幅恩鈍瓦英文原版糖代謝英文原版糖代謝 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. 撅榨旬疥膊劉掘淵壯介熾猴皚咐滴拽胡芽斥越揉診怔刪帕夠賭洲譬辮鍘芍英文原版糖代謝英文原版糖代謝GlutamateGlutamatea-ketoglutaratea-