课件：第章-糖代谢.ppt

Part ,Metabolism and its Regulation,Metabolism-Overview,Metabolism is a feature of life Metabolism consists of catabolism & anabolism Catabolism: degradative pathways Usually energy-yielding! Anabolism: biosynthetic pathways energy-requiring! Basic procedure of metabolism Digestion & absorption Intermediary metabolism Excretion,Outline,Carbohydrate Metabolism Lipid Metabolism Biological Oxidation Amino Acid Metabolism Nucleotide Metabolism Integration of Metabolism,Chapter 4,Metabolism of Carbohydrates,Chemistry of Carbohydrate,Carbohydrates Classification Momosaccharide Oligosaccharide Polysaccharide Glycoconjugate,2. Oligosaccharide 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),Starch,Glycogen,Cellulose,4. Glycoconjugate,糖与非糖物质的结合物 常见的结合糖 糖蛋白(glycoprotein) 糖脂 (glycolipid),4.1 Introduction,Functions of carbohydrate Digestion & Absorption Overview of carbohydrate metabolism,1. Functions of Carbohydrate,Providing energy Providing carbon Acting as structural components Special functions,2. Digestion & Absorption,Digestion Location： small intestine Procedure Products：monosaccharide(Glu, Gal, F) Absorption Location： small intestine 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 + Gal,3. Overview of Carbohydrate Metabolism,Glucose transporter(GLUT),葡萄糖,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 Anaerobic Catabolism of Carbohydrates,1. Procedure of Glycolysis,Glycolysis: Glucose Lactate + ATP anaerobic condition Two Phases G2 pyruvate pyruvatelactate,First phase：GPyruvate,Reaction 1 phosphorylation of glucose,激 酶(kinase),ATP + 底物 底物-P + ADP (高能磷酸化合物) 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,己糖激酶(hexokinase, HK) 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,Reaction 2,Rx3: 6-phosphofructokinase-1 (PFK-1),Rx 4: Aldolase,C6 cleaves to 2 C3s (DHAP, Gly-3-P),Rx 5: Triose Phosphate Isomerase,DHAP converted to Gly-3-P,Rx 6: Gly-3-Dehydrogenase,Gly-3P is oxidized to 1,3-BPG,Reaction 7,底物水平磷酸化 (substrate-level phosphorylation),定义： ADP/GDP 磷酸化为ATP/GTP与底物 的氧化作用直接偶联。 机制：底物分子内部能量重新分布，形成 高能键 区别于氧化磷酸化,Rx 8: Phosphoglycerate Mutase,Phosphoryl group from C-3 to C-2,Rx 9: Enolase,2-PG to PEP,Rx10: Pyruvate Kinase,Second Phase：PyruvateLactate,Features of Glycolysis,Location-cytosol Energy-yielding ：2ATP Key enzymes：HK, PFK-1, pyruvate kinase The fate of NADH+H+ anaerobic is oxidized by LDH to provide NAD+ aerobicelectron transfer chain The fate of pyruvate anaerobic LDH makes lactate aerobic TCA,2. Regulation of Glycolysis,Rate-limiting enzymes HK PFK-1 Pyruvate kinase Pattern of regulation Allosteric regulation Covalent modification,PFK-1,Allosteric regulation ActivatorsAMP, ADP, F-1,6-2P, F-2,6-2P InhibitorsATP，citrate PFK-2= PFK-2 + FBP-2 Covalent modification of PFK-2 Glucagon+PKAPFK-2F-2,6-2P Glycolysis,Pyruvate Kinase,变构调节：激活剂F-1,6-2P; 抑制剂ATP, Ala 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 & GK,Allosteric Inhibitors HK: G-6-P GK: acyl-CoA Aim of regulation ATP Glycolysis ATP Glycolysis ,3. 糖酵解的生理功能,迅速提供能量，对肌肉收缩特别重要 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 Carbohydrate,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。 是糖氧化的主要方式,1. Procedure of Aerobic Oxidation,Three phases Glycolytic pathway：G2 Pyruvate cytosol Pyruvateacetyl CoA： mitochondria TCA & oxidative phosphorylation：mitochondria,(1) Oxidative Decarboxylation of Pyruvate,HSCoA,CoA,辅酶A,丙酮酸脱氢酶复合体,E1 ：丙酮酸脱氢酶 TPP E2 ：转乙酰化酶 硫辛酸 E3 ：二氢硫辛酰胺脱氢酶 FAD、NAD+,(2)Tricarboxylic Acid Cycle(TCA cycle）,Citrate cycle , Krebs cycle,Reaction 1 : Citrate Synthase,Rx 2: Aconitase,Isomerization of Citrate to Isocitrate,Rx3: The First Oxidative Decarboxylation,Rx4: Second Oxidative Decarboxylation,Rx 5: Succinyl-CoA Synthetase,A substrate-level phosphorylation,Reaction 6 An oxidation involving FAD,Rx 7: Fumarase,Hydration across the double bond,Rx 8: Malate Dehydrogenase,An NAD+-dependent oxidation,Features of TCA Cycle,Location：mitochondria 4 dehydrogenation：3 NADH+H+ ， 1FADH2 2 decarboxylation： 2CO2 1 substrate-level phosphorylation：1GTP Energy-yielding: 12ATP 3X 3ATP + 1X 2ATP + 1ATP=12ATP Irreversible:citrate synthase, isocitrate dehydrogenase, - ketoglutarate dehydrogenase complex Intermediates acts as catalysts,True or False?,通过TCA循环可以生成柠檬酸/琥珀酸/草酰乙酸( ) 柠檬酸/琥珀酸/草酰乙酸在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,是三大营养素的最终代谢通路 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) 提供生物合成的前体 为呼吸链提供还原当量(NADH+H+, FADH2),2. Features of Aerobic Oxidation,Location：cytosolmitochondria 7 key enzymes Providing energy 1st phase 2nd phase 3rd phase 22X3(2X2) + 2X3 + 2X12 =38/36ATP,3. Regulation of Aerobic Oxidation,Regulation of glycolysis Regulation of pyruvate dehydrogenase complex Regulation of TCA cycle,Regulation of Pyruvate Dehydrogenase Complex,Allosteric regulation ActivatorsAMP, ADP, NAD+ Inhibitorsacetyl CoA、NADH+H+、ATP Covalent modification,三羧酸循环的调节,异柠檬酸脱氢酶和-酮戊二酸脱氢酶 激活剂 抑制剂 异柠 NAD+, Ca2+,ADP NADH ,ATP -酮 NAD+ ,Ca2+ NADH ,ATP,琥珀酰CoA 氧化磷酸化的速率,Ca2+,Why regulate aerobic oxidation?,To meet needs of energy ATP aerobic oxidation ATP aerobic oxidation,思考题,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,6/10 9/10； 7/10 10/10 9/10 周六 1-2节 N1-B205,4.4 Pentose Phosphate Pathway,Definition：G pentose-P + NADPH+H+ pentose-P F-6-P + Gly-3-P,1. Procedure,Two phases Oxidative reactions pentose-P，NADPH+H+，CO2 Nonoxidative reactions a series of group transfer,The First Phase,The Second Phase,C5,C5,C5,C3,C3,C6,C6,C7,C4,2C,2C,3C,3C5 2C6+ C3,基团转移反应,2. Features of Pentose Phosphate Pathway,Location：cytosol Group transfer Products：ribose-5-P & NADPH Key enzyme Glucose-6-phosphate dehydrogenase inhibitorNADPH,3. 磷酸戊糖途径的生理意义,为核酸的生物合成提供核糖 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,A AH2 2G-SH G-S-S-G NADP+ NADPH+H+,还原型,氧化型,4.5 Glycogenesis and Glycogenolysis,糖原(glycogen) 是动物体内糖的储存形式, 是机体能迅速动用的能量储备 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 Glycogen,-1,4-糖苷键 -1,6-糖苷键 非还原端,1. Glycogenesis,Glycogenesis： GGlycogen Location Tissues：liver & muscle Cell：cytosol Procedure GG-6-P G-6-PG-1-P synthesis of UDPG synthesis of glycogen,G-6-PG-1-P,磷酸葡萄糖变位酶,UDPG (uridine diphophate glucose),Active form of G (G donor） Other active forms：acetyl-CoA， ATP,Synthesis of Glycogen,Glycogenn + UDPG Glycogenn+1+ UDP Glycogen primer Branching enzyme,glycogen synthase,UDP,ATP,UTP,ADP,Features of Glycogenesis,Donor of glucose：UDPG Key enzyme：glycogen synthase Energy-requiring：2ATP Glycogen primer,2. Glycogenolysis,Definition：Liver glycogenG Location：cytosol Procedure : from non-reducing end Glycogen G-1-P G-6-P Liver： Muscle：glycolysis/aerobic oxidation Key enzyme：phosphorylase Debranching enzyme Products: G-1-P(85%) + G(15%）,phosphorylase,glucose-6-phosphatase,G,Glycogen Phosphorylase,3. Regulation of Glycogenesis & Glycogenolysis,Key enzymes Glycogen synthase(GS) Glycogen phosphorylase(GP) Pattern of regulation covalent modification allosteric regulation,Covalent Modification,GS GS-P (+) (-) GP GP-P (-) (+) Cascade system Amplification Every level can be regulated,共价修饰调节特点,两种酶磷酸化或去磷酸化后活性变化相反 快速调节 具有级联放大效应，效率高 受激素调节 胰高糖原分解，糖原合成 ,Allosteric Regulation,GS activators- ATP, G-6-P GP activator-AMP inhibitors-ATP, G-6-P Ca2+,思考题,1分子糖原通过糖酵解净生成( )分子ATP?,Glycogen is very limited,210mg G/kg/h 210 X 50kg X 10h=105g G,4.6 Gluconeogenesis,Definition non-carbohydratesglucose/glycogen Substrates lactate glycerol glucogenic amino acids Location Tissues： liver , kidney Cell：cytosolmitochondria,1. Gluconeogenic Pathway PyruvateGlucose, PyruvatePEP,胞液、线粒体,线粒体,Energy-requiring：2ATP How oxaloacetate goes into mito from cytosol? oxaloacetatemalate oxaloacetateAsp Source of NADH+H+ lactate：LDH glucogenic AA ：NADH+H+ in mito,TCA/-oxidation, F-1,6-2P F-6-P,6-,-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,甘油：3-磷酸甘油磷酸二羟丙酮 乳酸：丙酮酸草酰乙酸天冬氨酸 Ala等生糖AA: 丙酮酸草酰乙酸苹果酸 生糖AA：TCA中间产物草酰乙酸苹果酸,二、糖异生的调节,两个底物循环(substrate cycle) F-6-PF-1,6-2P PEP 丙酮酸 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,饥饿：胰高PKAPFK-2 F-2,6-2P糖异生 饥饿：胰高F-2,6-2PF-1,6-2P 糖酵解,3. 糖异生的生理意义,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 补充肝糖原: 三碳途径 G三碳化合物(丙酮酸、乳酸) 糖原 调节酸碱平衡,G,4. Lactate Cycle (Cori Cycle）,乳酸循环的形成是由于肝和肌肉中酶的特点不同 耗能: 6ATP 生理意义 避免乳酸的损失