《第4章-糖代谢说课材料.ppt》由会员分享，可在线阅读，更多相关《第4章-糖代谢说课材料.ppt（136页珍藏版）》请在taowenge.com淘文阁网|工程机械CAD图纸|机械工程制图|CAD装配图下载|SolidWorks_CaTia_CAD_UG_PROE_设计图分享下载上搜索。
1、第4章-糖代谢Outlinew Carbohydrate Metabolismw Lipid Metabolismw Biological Oxidationw Amino Acid Metabolismw Nucleotide Metabolismw Integration of MetabolismChapter 4MetabolismofCarbohydrates Chemistry of Carbohydratew Carbohydratesw Classification Momosaccharide Oligosaccharide Polysaccharide Glycoconju
2、gate2.Oligosaccharidew Common disaccharide麦芽糖(maltose)：GluGlu蔗糖(sucrose)：GluF乳糖(lactose)：GluGal 3.Polysaccharide 淀粉(starch)纤维素(cellulose)糖原(glycogen)StarchGlycogenCellulose 4.Glycoconjugatew糖与非糖物质的结合物 w常见的结合糖糖蛋白(glycoprotein)糖脂(glycolipid)4.1 Introductionw Functions of carbohydratew Digestion&Absorp
3、tionw Overview of carbohydrate metabolism 1.Functions of Carbohydratew Providing energyw Providing carbon w Acting as structural componentsw Special functions 2.Digestion&Absorptionw Digestion Location：small intestine Procedure Products：monosaccharide(Glu,Gal,F)w Absorption Location：small intestine
4、Type：monosaccharide Mechanism：active absorption淀 粉麦芽糖 麦芽三糖 -临界糊精 异麦芽糖 40%25%30%5%葡萄糖-葡萄糖苷酶-临界糊精酶 -淀粉酶 蔗糖G+F 乳糖G+Gal3.Overview of Carbohydrate Metabolismw Glucose transporter(GLUT)糖原H2O CO2乳酸磷酸戊糖途径 合成 分解糖异生有氧氧化无氧分解8.2 AnaerobicCatabolismofCarbohydrates 1.Procedure of GlycolysiswGlycolysis:Glucose Lac
5、tate+ATP anaerobic conditionwTwo PhasesG2 pyruvate pyruvatelactate First phase：GPyruvateReaction1phosphorylation of glucose激 酶(kinase)w ATP +底物 底物-P +ADP(高能磷酸化合物)w 特点 催化不可逆反应 需要Mg2+受激素调控己糖激酶和葡萄糖激酶w 己糖激酶(hexokinase,HK)w 葡萄糖激酶(glucosekinase,GK)部位 专一性 G的亲和力 HK 各组织 低 高 GK 肝 高 低 Reaction2Rx3:6-phosphofru
6、ctokinase-1(PFK-1)Rx 4:AldolaseC6 cleaves to 2 C3s(DHAP,Gly-3-P)Rx 5:Triose Phosphate IsomeraseDHAP converted to Gly-3-P Rx 6:Gly-3-DehydrogenaseGly-3P is oxidized to 1,3-BPG Reaction 7底物水平磷酸化(substrate-level phosphorylation)w 定义：ADP/GDP 磷酸化为ATP/GTP与底物 的氧化作用直接偶联。w 机制：底物分子内部能量重新分布，形成 高能键 w 区别于氧化磷酸化Rx
7、 8:Phosphoglycerate MutasePhosphoryl group from C-3 to C-2 Rx 9:Enolase2-PG to PEP Rx10:Pyruvate KinaseSecond Phase：PyruvateLactateFeatures of GlycolysiswLocation-cytosolwEnergy-yielding：2ATP wKey enzymes：HK,PFK-1,pyruvate kinase wThe fate of NADH+H+anaerobic is oxidized by LDH to provide NAD+aerobi
8、celectron transfer chainw The fate of pyruvateanaerobic LDH makes lactateaerobic TCA 2.Regulation of Glycolysisw Rate-limiting enzymes HK PFK-1 Pyruvate kinasew Pattern of regulation Allosteric regulation Covalent modificationPFK-1wAllosteric regulation ActivatorsAMP,ADP,F-1,6-2P,F-2,6-2PInhibitorsA
9、TP，citratewPFK-2=PFK-2+FBP-2wCovalent modification of PFK-2 wGlucagon+PKAPFK-2F-2,6-2P Glycolysis Pyruvate Kinasew变构调节：激活剂F-1,6-2P;抑制剂ATP,Alaw共价修饰调节丙酮酸激酶 (+)丙酮酸激酶-P (-)蛋白激酶磷蛋白磷酸酶胰高+HK&GKw Allosteric Inhibitors HK:G-6-P GK:acyl-CoA w Aim of regulation ATP Glycolysis ATP Glycolysis 3.糖酵解的生理功能 w迅速提供能量，
10、对肌肉收缩特别重要 w是一些细胞在氧供应正常情况下的重要供能途径 成熟红细胞 代谢活跃的细胞：神经、白细胞、骨髓 4.3 Aerobic Oxidation of Carbohydratew概念：葡萄糖在有氧条件下，彻底氧化成H2O和CO2，并释放出大量能量的过程。w是糖氧化的主要方式 1.Procedure of Aerobic Oxidationw Three phasesGlycolytic pathway：G2 Pyruvate cytosolPyruvateacetyl CoA：mitochondria TCA&oxidative phosphorylation：mitochondr
11、ia (1)Oxidative Decarboxylation of PyruvateHSCoA CoA辅酶A丙酮酸脱氢酶复合体wE1：丙酮酸脱氢酶 TPP wE2：转乙酰化酶 硫辛酸wE3：二氢硫辛酰胺脱氢酶 FAD、NAD+(2)Tricarboxylic Acid Cycle(TCA cycle）Citrate cycle,Krebs cycleReaction 1:Citrate SynthaseRx 2:AconitaseIsomerization of Citrate to Isocitrate Rx3:The First Oxidative DecarboxylationRx4:
12、Second Oxidative Decarboxylation Rx 5:Succinyl-CoA SynthetaseA substrate-level phosphorylation Reaction 6An oxidation involving FADRx 7:FumaraseHydration across the double bond Rx 8:Malate DehydrogenaseAn NAD+-dependent oxidation Features of TCA CyclewLocation：mitochondriaw4 dehydrogenation：3 NADH+H
13、+，1FADH2 2 decarboxylation：2CO2 1 substrate-level phosphorylation：1GTPw Energy-yielding:12ATP 3X 3ATP+1X 2ATP+1ATP=12ATPwIrreversible:citrate synthase,isocitrate dehydrogenase,-ketoglutarate dehydrogenase complexw Intermediates acts as catalystsTrue or False?w 通过TCA循环可以生成柠檬酸/琥珀酸/草酰乙酸()w柠檬酸/琥珀酸/草酰乙酸在
14、TCA循环中被直接氧化()TCA cycle 的总反应三羧酸循环的生理意义 w是三大营养素的最终代谢通路 w是糖、脂肪、氨基酸代谢联系的枢纽 糖脂肪 AATCA的中间产物草酰乙酸糖 葡萄糖非必需AA(Asp,Glu)w提供生物合成的前体 w为呼吸链提供还原当量(NADH+H+,FADH2)2.Features of Aerobic Oxidationw Location：cytosolmitochondriaw 7 key enzymesw Providing energy 1st phase 2nd phase 3rd phase22X3(2X2)+2X3 +2X12 =38/36ATP 3
15、.Regulation of Aerobic Oxidationw Regulation of glycolysisw Regulation of pyruvate dehydrogenase complexw Regulation of TCA cycleRegulation of Pyruvate Dehydrogenase Complexw Allosteric regulation ActivatorsAMP,ADP,NAD+Inhibitorsacetyl CoA、NADH+H+、ATP w Covalent modification三羧酸循环的调节w异柠檬酸脱氢酶和-酮戊二酸脱氢酶
16、 激活剂 抑制剂异柠 NAD+,Ca2+,ADP NADH,ATP-酮 NAD+,Ca2+NADH,ATP,琥珀酰CoAw氧化磷酸化的速率Ca2+Why regulate aerobic oxidation?w To meet needs of energyATP aerobic oxidationATP aerobic oxidation 思考题w 比较糖酵解和有氧氧化的异同（底物、产物、条件、部位、基本过程、产能、限速酶、生理意义）调课通知w 6/10 9/10；7/10 10/10w 9/10 周六 1-2节 N1-B2054.4 Pentose Phosphate Pathwayw D
17、efinition：G pentose-P+NADPH+H+pentose-P F-6-P+Gly-3-P 1.Procedurew Two phasesOxidative reactions pentose-P，NADPH+H+，CO2 Nonoxidative reactions a series of group transferThe First PhaseThe Second Phase C5C5C5C3C3C6C6C7C42C2C3Cw 3C5 2C6+C3基团转移反应2.Features of Pentose Phosphate Pathwayw Location：cytosol
18、w Group transfer w Products：ribose-5-P&NADPHw Key enzymeGlucose-6-phosphate dehydrogenase inhibitorNADPH 3.磷酸戊糖途径的生理意义w为核酸的生物合成提供核糖 w提供NADPH+H+作为供氢体参与多种代谢反应是体内许多合成代谢的供氢体 参与体内羟化反应 维持谷胱甘肽(GSH)的还原状态 例：蚕豆病 AAH22G-SHG-S-S-GNADP+NADPH+H+还原型氧化型4.5 Glycogenesis and Glycogenolysis w糖原(glycogen)是动物体内糖的储存形式,是机
19、体能迅速动用的能量储备w种类肝糖原：70100g 血糖的重要来源肌糖原：180300g 肌肉收缩的应急能源 Structure of Glycogenw-1,4-糖苷键 w-1,6-糖苷键 w 非还原端 1.GlycogenesiswGlycogenesis：GGlycogenw Location Tissues：liver&muscle Cell：cytosolw Procedure GG-6-P G-6-PG-1-P synthesis of UDPG synthesis of glycogenG-6-PG-1-P磷酸葡萄糖变位酶UDPG(uridine diphophate glucos
20、e)w Active form of G(G donor）w Other active forms：acetyl-CoA，ATPSynthesis of Glycogenw Glycogenn+UDPG Glycogenn+1+UDPw Glycogen primerw Branching enzyme glycogen synthaseUDPATPUTPADPFeatures of GlycogenesiswDonor of glucose：UDPG wKey enzyme：glycogen synthase wEnergy-requiring：2ATP wGlycogen primer2.
21、Glycogenolysis wDefinition：Liver glycogenGwLocation：cytosolwProcedure:from non-reducing end Glycogen G-1-P G-6-P Liver：Muscle：glycolysis/aerobic oxidationw Key enzyme：phosphorylasew Debranching enzymew Products:G-1-P(85%)+G(15%）phosphorylase glucose-6-phosphataseGGlycogen Phosphorylase3.Regulation o
22、f Glycogenesis&Glycogenolysisw Key enzymes Glycogen synthase(GS)Glycogen phosphorylase(GP)w Pattern of regulation covalent modification allosteric regulationCovalent Modificationw GS GS-P (+)(-)w GP GP-P (-)(+)w Cascade system Amplification Every level can be regulated共价修饰调节特点w两种酶磷酸化或去磷酸化后活性变化相反 w快速
23、调节 w具有级联放大效应，效率高 w受激素调节 胰高糖原分解，糖原合成 Allosteric Regulationw GS activators-ATP,G-6-Pw GP activator-AMP inhibitors-ATP,G-6-Pw Ca2+思考题w 1分子糖原通过糖酵解净生成()分子ATP?Glycogen is very limitedw 210mg G/kg/hw 210 X 50kg X 10h=105g G4.6 GluconeogenesiswDefinition non-carbohydratesglucose/glycogenwSubstrateslactategl
24、ycerolglucogenic amino acidsw LocationTissues：liver,kidneyCell：cytosolmitochondria 1.Gluconeogenic Pathway PyruvateGlucose PyruvatePEP 胞液、线粒体线粒体wEnergy-requiring：2ATPw How oxaloacetate goes into mito from cytosol?oxaloacetatemalateoxaloacetateAspw Source of NADH+H+lactate：LDHglucogenic AA：NADH+H+in
25、mito TCA/-oxidation F-1,6-2P F-6-P6-1 果糖双磷酸酶-1 G-6-P G葡萄糖-6-磷酸酶其它原料的糖异生途径w甘油：3-磷酸甘油磷酸二羟丙酮w乳酸：丙酮酸草酰乙酸天冬氨酸 w Ala等生糖AA:丙酮酸草酰乙酸苹果酸w生糖AA：TCA中间产物草酰乙酸苹果酸 二、糖异生的调节w 两个底物循环(substrate cycle)F-6-PF-1,6-2PPEP 丙酮酸w 无效循环(futile cycle)糖酵解糖异生糖酵解糖异生糖异生调节举例w饥饿：胰高PKAPFK-2 F-2,6-2P糖异生w饥饿：胰高F-2,6-2PF-1,6-2P 糖酵解 3.糖异生的生理
26、意义w维持血糖水平恒定脑、红细胞、骨髓、神经等 G饥饿：脂肪分解甘油G 蛋白质分解生糖AAG w补充肝糖原:三碳途径 G三碳化合物(丙酮酸、乳酸)糖原 w调节酸碱平衡G4.Lactate Cycle(Cori Cycle）w乳酸循环的形成是由于肝和肌肉中酶的特点不同 w 耗能:6ATPw 生理意义 避免乳酸的损失 防止因乳酸堆积引起酸中毒 思考题w 比较糖异生和糖酵解的异同 （部位、途径、限速酶、能量、生理意义）w 谷氨酸是如何异生成糖的？4.7 血糖及其调节w血糖：血中的葡萄糖 w血糖水平：血中葡萄糖浓度w正常血糖浓度：3.896.11mmol/Lw血糖的来源和去路 1.血糖的来源和去路血糖
27、食物糖肝糖原非糖物质氧化分解糖原合成磷酸戊糖途径等脂类、氨基酸代谢消化吸收分解糖异生CO2+H2O肝、肌糖原其它糖脂肪、氨基酸等血糖恒定的生理意义w保证重要器官的能量供应 脑组织正常情况下主要依赖葡萄糖供能 红细胞完全依赖葡萄糖获能 骨髓及神经组织经常利用葡萄糖供能 2.血糖水平的调节w血糖水平恒定是糖、脂肪、氨基酸代谢协调的结果，也是肝、肌肉、脂肪组织等各器官组织代谢协调的结果 w进食：G 糖的氧化分解，糖原合成 糖脂肪w 饥饿：G 3.63.8mmol/L 肝糖原G，AA、甘油Gw三个水平：神经、激素、酶 GG激素的调节w 降低血糖的激素 胰岛素(insulin)w 升高血糖的激素胰高血糖
28、素(glucagon)糖皮质激素 肾上腺素胰 岛 素w促进葡萄糖转运进入肌肉、脂肪组织 w糖原合成，糖原分解 w糖的有氧氧化w肝糖异生 w脂肪动员 胰高血糖素 -与胰岛素拮抗w肝糖原分解，糖原合成 w糖酵解 w糖异生w脂肪动员 耐糖现象w葡萄糖耐量 (glucose tolerance)人体对摄入的葡萄糖有耐受能力w糖耐量实验(glucose tolerance test,GTT)3.血糖水平异常w高血糖及糖尿症（hyperglycemia and glucosuria）w低血糖（hypoglycemia）此课件下载可自行编辑修改，仅供参考！此课件下载可自行编辑修改，仅供参考！感谢您的支持，我们努力做得更好！谢谢感谢您的支持，我们努力做得更好！谢谢