高中生物奧賽輔導生化——糖代謝

1、生物化學 淀粉酶淀粉酶纖維素酶纖維素酶半纖維素酶半纖維素酶果膠酶果膠酶a a- -淀粉酶淀粉酶b-b-淀粉酶淀粉酶葡萄糖淀粉酶葡萄糖淀粉酶異淀粉酶異淀粉酶麥芽糖酶麥芽糖酶蔗糖酶蔗糖酶乳糖酶乳糖酶1.1 糖類水解酶1.2 糖類在人體中的消化糖類食物糖類食物唾液淀粉酶唾液淀粉酶咀嚼、部分水解咀嚼、部分水解HCl有限水解有限水解胰淀粉酶胰淀粉酶a a-糊精、麥芽糖和少量葡萄糖糊精、麥芽糖和少量葡萄糖糖苷酶糖苷酶單糖單糖吸收吸收 糖的吸收就是指游離的葡萄糖（單糖）進入糖的吸收就是指游離的葡萄糖（單糖）進入到生物體內（細胞內）的過程。到生物體內（細胞內）的過程。糖的吸收方式糖的吸收方式主動運輸主動運輸促

2、進擴散促進擴散基團轉位基團轉位1.3 糖的吸收血糖血糖80120 mg/100 ml4070， 120180低低 高高血糖的來源、去向u Glucose is very soluble source of quick and ready energy.u It is a relatively stable and easily transported.u Glucose is the only source of energy in red blood cells酵解（酵解（glycolysis): 是酶將是酶將葡萄糖葡萄糖降解成降解成丙酮酸丙酮酸并伴隨著并伴隨著生成生成ATP的過程。它是動物

3、、植物、的過程。它是動物、植物、微生物細胞中葡萄糖分解產(chǎn)生能量的微生物細胞中葡萄糖分解產(chǎn)生能量的共同代共同代謝謝途徑。途徑。發(fā)酵（發(fā)酵（fermentation)：厭氧有機體把酵解生成厭氧有機體把酵解生成的的NADH中的氫交給中的氫交給丙酮酸，生成乳酸；丙酮酸，生成乳酸；或或丙酮酸脫羧生成的丙酮酸脫羧生成的乙醛，生成乙醇乙醛，生成乙醇。2.1 概念 Glycolysis 糖酵解是葡萄糖生成丙酮酸的代謝途徑糖酵解是葡萄糖生成丙酮酸的代謝途徑糖酵解概況丙酮酸丙酮酸Anaerobic conditionsAerobic conditionsExercising muscleYeastThe fate

4、 of glucose is varies with physiological conditions, tissues, and organisms.葡萄糖葡萄糖2. 糖酵解是無氧條件下的反糖酵解是無氧條件下的反應應(fermentations);3. 糖酵解發(fā)生的部位是糖酵解發(fā)生的部位是細胞質細胞質；2.2.2 糖酵解概況Preparatary phasePayoff phase(產(chǎn)能產(chǎn)能)22 ATP2.2.2 糖酵解概況4糖酵解途徑包括兩個階段糖酵解途徑包括兩個階段(耗能耗能) 2ATPNet: 2 ATP； a limited amount5. 中間代謝產(chǎn)物是磷酸化的中間代謝產(chǎn)物是磷

5、酸化的;6. 化學變化的三種類型；化學變化的三種類型；7. 糖酵解是嚴密調控的糖酵解是嚴密調控的.碳原子途徑碳原子途徑磷酸途徑磷酸途徑氧化還原反應的電子途徑氧化還原反應的電子途徑2.2.2 糖酵解概況2.2.2 糖酵解概況Glucose is phosphorylated. The negative charge concentrates glucose in the cell and glucose becomes less stable. (P ，C ，e )2.2.2 糖酵解概況8. Types of reactions occurring in glycolysisPhosphoryl

6、 group transfer: kinase(激酶激酶);磷酸化酶磷酸化酶+ATPRROHO-POOO-+ADP+H+KinaseABCD激酶激酶2.2.2 糖酵解概況8. Types of reactions occurring in glycolysisPhosphoryl group shift: mutase（變位酶）（變位酶）RCMutaseO HHC H2O-POOO-RCOHC H2OHO-PO-OPhosphoryl shift. A phosphoryl group is shifted from one oxygen atom to another within a mo

7、lecule by a mutase.2.2.2 糖酵解概況8. Types of reactions occurring in glycolysisIsomerization: isomerase(異構酶異構酶);RIsomeraseCCH2OHORCCOHHOHIsomerization. A ketose (酮糖） is converted into an aldose （醛醣）, or vice versa, by an isomerase.2.2.2 糖酵解概況8. Types of reactions occurring in glycolysisDehydration: dehy

8、dratase（enolase, 烯醇化酶）烯醇化酶）Dehydration. A molecule of water is eliminated by a dehydratase.HDehydrataseCCO HHHHCCH+H2O2.2.2 糖酵解概況8. Types of reactions occurring in glycolysisAldol cleavage: aldolase（醛縮酶）（醛縮酶）Aldol cleavage. A carbon-carbon bond is split in a reversal of an aldol condensation by an a

9、ldolase.RAldolaseCCOHHCHOHRORCCOHCHOHROH Phosphoryl group transfer: kinase; Phosphoryl group shift: mutase（變位酶）（變位酶）; Isomerization: isomerase; Dehydrogenation: dehydrogenase（脫氫酶）（脫氫酶）; Dehydration: dehydratase (enolase，烯醇化酶，烯醇化酶); Aldol cleavage: aldolase（醛縮酶）（醛縮酶）.糖酵解概況Preparatory phase:Phosphoryl

10、ation of glucose and its conversion to glyceraldehyde-3-phosphatePayoff phaseConversion of glyceraldehyde-3-phosphate to pyruvate and the coupled formation of ATP2.2.3 糖酵解的反應葡萄糖葡萄糖葡萄糖葡萄糖-6-磷酸磷酸果糖果糖-6-磷酸磷酸果糖果糖-1,6-二磷酸二磷酸甘油醛甘油醛-3-磷酸磷酸二羥丙酮磷酸二羥丙酮磷酸甘油醛甘油醛-3-磷酸磷酸二羥丙酮磷酸二羥丙酮磷酸1,3-二磷酸甘油酸二磷酸甘油酸 3-磷酸甘油酸磷酸甘油酸 2

11、-磷酸甘油酸磷酸甘油酸磷酸烯醇式丙酮酸磷酸烯醇式丙酮酸丙酮酸丙酮酸 帶有負電荷的磷酸基團使中間產(chǎn)物具有極性，從而使這些產(chǎn)物不易透過脂膜而失散。 磷酸基團在各反應步驟中，對酶來說，起到信號基團的作用，有利于與酶結合而被催化。 磷酸基團經(jīng)酵解作用后，最終形成ATP的末端磷酸基團，因此具有保存能量的作用。Intermediary metabolites are phosphated（磷酸化的）(1) Glucose is Phosphorylated First to Enter GlycolysisG= -4.0 kcal mol-1Hexokinase己糖激酶(1) Glucose is Pho

12、sphorylated First to Enter Glycolysis己糖激酶與葡萄糖結合時的構象變化己糖激酶與葡萄糖結合時的構象變化(2) Glucose-6-P Isomerizes from an Aldose to a Ketose G= 0.40 kcal/molPhosphoglucose Isomerase磷酸葡萄糖同分異構酶(2) Glucose-6-P Isomerizes from an Aldose to a Ketose Phosphoglucose IsomeraseThe enzyme opens the ring, catalyzes the isomeriz

13、ation, and promotes the closure of the five member ring. (3) Fructose-6-P is Further Activated by PhosphorylationPhosphofructokinasePFK（磷酸果糖激酶）G= -3.4 kcal mol-1The 2nd investment of an ATP in glycolysis. 磷酸果糖激酶是一種變構酶，糖酵解的速率糖酵解的速率嚴格地依賴該酶的活力水平，它是哺乳動物糖酵解途徑最重要的調控關鍵酶調控關鍵酶。 肝中PFK受高濃度的ATP的抑制。ATP結合于調節(jié)部位結合于

14、調節(jié)部位。ATP對該酶的別構抑制效應可被AMP解除。因此ATP/AMP的比例關系對此酶有明顯的調節(jié)作用。(3) Fructose-6-P is Further Activated by Phosphorylation(4) Fructose-1,6-Bisphosphate is Cleaved (lysed) in the MiddleAldolase (醛縮酶）G= 5.7 kcal mol-1Reverse aldol condensation; converts a 6 carbon atom sugar to 2 molecules, each containing 3 carbon

15、 atoms.果糖果糖-1，6-二磷酸二磷酸FBP二羥丙酮磷酸二羥丙酮磷酸（DHAP）甘油醛甘油醛-3-磷酸磷酸（GAP）(5) Triose phosphate InterconvertTriose phosphate isomerase丙糖磷酸異構酶 ，TIM二羥丙酮磷酸二羥丙酮磷酸（DHAP）甘油醛甘油醛-3-磷酸磷酸（GAP）G = 1.8 kcal mol-1甘油醛甘油醛-3-磷酸磷酸(5) Triose phosphate InterconvertAll the DHAP is converted to glyceraldehyde 3-phosphate（GAP）. Althou

16、gh, the reaction is reversible it is shifted to the right since glyceraldehyde 3-phosphate is a substrate for the next reactions of glycolysis. Thus, both 3-carbon fragments are subsequently oxidized.(5) Triose phosphate Interconvert二羥丙酮磷酸二羥丙酮磷酸（DHAP）甘油醛甘油醛-3-磷酸磷酸（GAP）單烯二羥負單烯二羥負離子中間體離子中間體G = 1.8 kca

17、l mol-1(6) Glyceraldehyde-3-phosphate is OxidizedGlyceraldehyde 3-phosphate DH甘油醛甘油醛-3-磷酸脫氫酶，磷酸脫氫酶，GAPDHThe energy yielding phaseG = 1.5 kcal mol-11，3二二磷酸甘磷酸甘油酸油酸(6) Glyceraldehyde-3-phosphate is OxidizedGAPDH碘乙酸碘乙酸無活性的酶無活性的酶甘油醛-3-磷酸脫氫酶 甘油醛-3-磷酸脫氫酶（GAPDH）能夠利用砷酸砷酸代替磷酸磷酸參加反應，生成3-P-甘油酰砷酸甘油酰砷酸，這是一個高度不穩(wěn)定

18、的化合物， 在水溶液中，可立刻自發(fā)地分解為3-P-甘油酸和砷酸甘油酸和砷酸。 因此，砷酸不抑制糖酵解的繼續(xù)進行砷酸不抑制糖酵解的繼續(xù)進行，但它不它不能產(chǎn)生高能磷酸鍵能產(chǎn)生高能磷酸鍵。所以，砷酸是糖酵解中基質水平磷酸化的解偶聯(lián)劑解偶聯(lián)劑。(7) The anhydride phosphate in 1,3-BPG is used to generate ATPPhosphoglycerate Kinase （磷酸甘油酸激酶，PGK）Substrate-level phosphorylation （ 底物水平的磷酸化）G = -4.5 kcal mol-1Remember: 2 molecules

19、 of ATP are produced per glucose.1，3-二磷酸甘油酸二磷酸甘油酸3-磷酸甘油酸磷酸甘油酸u Mutase belongs to the isomerase family.(8) Phosphate reversibly shifts between C2 and C3 on glyceratePhosphate shiftPhosphoglycerate mutase磷酸甘油酸變位酶G = 1.1 kcal mol-13-磷酸甘油酸磷酸甘油酸2-磷酸甘油酸磷酸甘油酸 磷酸烯醇式丙酮酸，PEP has high phosphoryl group transfer

20、 potential （高基團轉移勢能）.(9) The Phosphoryl Group Transfer Potential is Markedly Elevated by DehydrationEnolase（烯醇化酶）G = 0.4 kcal mol-1Dehydration reaction(10) The Phosphate Group on PEP is Transferred to ADPPyruvate Kinase，丙酮酸激酶G = -7.5 kcal mol-1烯醇式烯醇式酮式酮式2nd example of substrate level phosphorylation

21、 （底物水平磷酸化）. The net yield from glycolysis （酵解） is 2 ATP.Substrate level phosphorylcation is the synthesis of ATP from ADP that is not linked to the electron transport system（電子傳遞系統(tǒng)）.PEP+ADPPyr+ATP(10) The Phosphate Group on PEP is Transferred to ADP紅血球紅血球標準態(tài)標準態(tài)Summary: G at each step of GlycolysisGl

22、ucosePyruvateGlucose + 2 Pi + 2 ADP + 2 NAD+ 2 pyruvate + 2 ATP + 2 NADH +2 H+The Energy released from the anaerobic conversion of glucose to pyruvate is -47 kcal mol-1. Under aerobic conditions much more chemical bond energy can be extracted from pyruvate.The question still remains: How is NAD+ sup

23、plied under anaerobic conditions? Or how is redox balance maintained?Summary: The Conversion of Glucose to Pyruvate2.2.4 丙酮酸的代謝去路lPyruvate reduced (還原) and NAD+ regenerated (生成);lCatalyzed by lactate dehydrogenase (乳酸脫氫酶);lThis happens in animal tissues when O2 is limited;lThis also happens in many

24、microorganisms (e.g., lactobacilli).(1) Pyruvate is the final electron acceptor in lactic acid fermentationWhat happens to the lactate after a run?uPyruvate decarboxylase 丙酮酸脫羧酶 (present only in those alcohol fermentative organisms) and alcohol dehydrogenase 乙醇脫氫酶 (present in many organisms includin

25、g human) catalyzes the two-step reactions.G0 = -10.46 kJ/mol(2) Acetaldehyde is the final electron acceptor in alcohol fermentationRemember! 酵解過程必須提供NAD+，而缺氧的情況下, NADH不能夠把H傳遞給電子傳遞鏈而產(chǎn)生NAD+；NADH的H可以選擇傳遞給產(chǎn)物從而使酵解過程得以進行從而產(chǎn)生能量。l碳原子途徑（碳骨架的去向）碳原子途徑（碳骨架的去向）:Glucose(6C)2pyruvate(3C)n磷原子途徑磷原子途徑 (ATP的變化的變化):消耗消

26、耗G6P 的形成的形成 1FBP的形成的形成 1產(chǎn)生產(chǎn)生1,3-二磷酸甘油酸的形成二磷酸甘油酸的形成 + 2PEP的形成的形成 + 2u氧化還原反應的電子途徑氧化還原反應的電子途徑:1,3-二磷酸甘油酸的形成二磷酸甘油酸的形成終產(chǎn)物終產(chǎn)物2 NADH + H+2.2.5 Overal balance of glycolysis2.2.6 Regulation of the Glycolytic pathwaynEnzyme reactions that have a significant negative G are often control sites.nIN glycolysis:nH

27、exokinase nPhosphofuctokinase(PFK)nPyruvate Kinaseare regulatory enzymes.nPFK is the most important. 磷酸果糖激酶催化的反應是糖酵解的限速反應。High levels of ATP inhibit, increased levels of AMP reverses the action of ATP.Citrate(檸檬酸） also inhibits PFK. High levels of citrate indicates that the cell is rich in biosynthe

28、tic precursors（生物合成前導物） emanating from the pathway. PFK is an allosteric enzyme糖酵解作用不僅是提供能量，也為生物合成提供碳骨架。糖酵解作用不僅是提供能量，也為生物合成提供碳骨架。 PFK is an allosteric enzyme 酶的可逆變構，磷酸化作用的調節(jié)及轉錄的控制根據(jù)不同情況下可在百萬之一秒、幾秒或幾小時內發(fā)生變化。. 糖原磷酸解轉變?yōu)樘窃姿峤廪D變?yōu)?-磷酸葡萄糖進入糖酵解磷酸葡萄糖進入糖酵解n這步反應是磷酸解而不是水解這步反應是磷酸解而不是水解.2.2.7

29、 其它糖進入糖酵解的途徑其它糖進入糖酵解的途徑2.2.7 其它糖進入糖酵解的途徑其它糖進入糖酵解的途徑Mutase 變位酶變位酶FructoseFructokinase（激酶）Fructose-1-PFBPFructose-1-P-kinaseFructose-1-P aldolase （醛縮酶）triose kinaseglyceraldehyde-3-phosphate (G3P) Fructose(果糖）果糖）enters glycolysis mainly via F-1-P pathway2.2.7 其它糖進入糖酵解的途徑其它糖進入糖酵解的途徑肝臟肝臟肌肉肌肉2.2.7

30、.4 Galactose （半乳糖）（半乳糖） enters glycolysis pathway via the galactose-glucose interconversion pathway （p87-88）GalactoseGalactose-1-phosphateUDP-GlucoseUDP-GalactoseGlucose-1-phosphateGlucose-6-phosphateUDP-4-keto-GlucosenIn adults:尿苷酰轉移酶尿苷酰轉移酶UDP-半乳糖半乳糖-4-差向異構酶差向異構酶UDP-Galactose4-epimeraseUDP-葡萄糖葡萄糖焦磷酸化酶焦磷酸化酶 Galactose enters glycolysis pathway via the galactose-glucose interconversion pathwayGalactoseG