生物化学教学课件：代谢调节

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1、Regulation of MetabolismRegulation Principles and strategies1 Integrated Neutrient, Energy and Information metablismPrinciples and strategies1 Integrated Neutrient, Energy and Information metablism2 Common Pathways3 Several kinds of reactions vs many kinds of chemicals 氧化还原氧化还原 基团转移基团转移 水解水解 合成合成 基团

2、脱加基团脱加 异构化异构化Principles and strategies4 Interchangable between carbonhydrates, lipid, AA, NtKey: G-6-P、Pyr、CH3COCoA,Frmarate 5 TCA is the heart of metablism6 ATP is the vector of energe7 Biodegradation provides:ATP, NADPH, building material for biosynthesis NADPH：dedicated to synthesis NADH, FADH2:

3、dedicated to production of ATPGlutaminaseGlutamine synthetase8 Biosynthesis and biodegradation are seperated and regulated differentially (catalysed by different enzymes)8 Biosynthesis and biodegradation are seperated and regulated differentially (catalysed by different enzymes)9 Coordinate of statu

4、ses 进食-饥饿循环Well-fed乳糜微粒门静脉9 Coordinate of statuses进食-饥饿循环Early fasting肝糖原肝细胞糖酵解维持了禁食早期的血糖水平9 Coordinate of statuses进食-饥饿循环肝糖原Fasting禁食后禁食后10-12小时机体主要依赖小时机体主要依赖乳酸、丙酮酸和丙氨酸为原料的乳酸、丙酮酸和丙氨酸为原料的肝糖异生作用提供能量。肝糖异生作用提供能量。脂肪酯解：脂肪酯解：脂肪的丙三醇用脂肪的丙三醇用于葡萄糖合成于葡萄糖合成蛋白质蛋白质/氨基酸的碳架为氨基酸的碳架为葡萄糖合成主要原料葡萄糖合成主要原料肌肉肌肉释放的谷氨氨酰胺为上皮细

5、胞淋巴细胞巨噬细胞所利用脂肪酸为肝外组织细胞提供能量，许多组织优先使用脂肪酸而不是葡萄糖，葡萄糖的合成和尿素合成紧密相关脂肪酸产生酮体，为糖异生提供能量Fat is easy and slim is hard!能量充足的时候，人类能够以远比基础热量需求高的速率消耗食物并储存能量；每天摄入超过热量消耗以外的2份黄油(100卡)将会导致每年体重增加10磅能量不足的时候，葡萄糖水平降低，胰岛素分泌减少，机体减少三碘甲状腺素的形成，降低基础代谢（减少25%）；1小时长跑（5-6miles）=2块方糖Obesity（肥胖）人体大部分脂肪直接来源于食物，只有一小部分在肝脏合成后运输到脂肪组织或者由脂肪细胞

6、合成Dieting：低糖生酮饮食方案Exercise：消耗肌糖、原肝糖原和脂肪保证血糖浓度长时间大强度运动中，运动前肌糖原储量决定了运动力枯竭的时间，是冲刺阶段的决定因素血糖，糖原和运动糖代谢和运动的关系无氧运动前必须有足够的肌糖原储量肝糖原，血糖，肌糖原，糖异生之间的关系糖原和运动的关系长期运动训练使机体组织中糖原增多 葡萄糖葡萄糖 酵解途径酵解途径 丙酮酸丙酮酸 有氧有氧 无无氧氧 H2O，CO2 乳酸乳酸 糖异生途径糖异生途径 乳酸、氨基酸、甘油乳酸、氨基酸、甘油 糖原糖原 肝糖原分解肝糖原分解 糖原糖原合成酶合成酶 磷酸戊糖途径磷酸戊糖途径 核糖核糖 + + NADPH+H+淀粉淀粉

7、消化与吸收消化与吸收 ATP Pregnancy：葡萄糖和氨基酸消耗的增加Cancer：葡萄糖酵解为肿瘤供能糖代谢在正常细胞和肿瘤细胞中的差异Warburg effect 肿瘤细胞依赖糖酵解通路产能的现象缺乏氧气对依赖氧化磷酸化产能的细胞来说是致命的糖代谢在正常细胞及干细胞中的差异低氧条件培养加强了干细胞的活力Liver diseases：尿素循环障碍，高血氨Kidney Diseases：氨基酸代谢氨基酸浓度增加，氮终产物储积Alcohol：产生乙醛和过多的NADH,抑制糖异生、抑制脂肪酸氧化、抑制三羧酸循环Enviromental ligandsSignal transductionLev

8、el of enzymesExpression regulationvs Protein degradationEnzymatic activity(Regulatory enzyme)Cellular structureMolecular Insight to Metablism RegulationCharacteristics of Regulatory Enzymes! Irreversible step! Requires energy! Often results in a phosphorylated compoundThe most responsive regulation

9、of metablism takes place at first reaction, which is usually irreversible and catalyzedby an allosteric enzyme. Rate-limiting step Committed step-Early step unique to a pathwayTypes of Regulatory Mechanisms Non-covalent interactions Covalent modifications Changes in abundance of the enzyme Allosteri

10、c Regulation Binding of allosteric effectors at allosteric sites affect catalytic efficiency of the enzyme, Allosteric Activators: Decrease Km; Increases VmaxSubstrates of pathwaysFeed-forward activatorsEnd products of pathways Feedback inhibitionIndicators of Energy Status&Conc.ATP/ADP/AMPNAD/NADHa

11、cetyl CoA Enzyme multiplicity（多样性）（多样性）Allosteric Regulation （变构调节）（变构调节）Isozymes（同工酶）（同工酶）End product feedback inhibitionConcerted inhibition（协调抑制）（协调抑制）Sequential feedbackInhibition（顺序反馈抑制）（顺序反馈抑制）Amino Acid Biosynthesis Is under Allosteric RegulationTypes of Regulatory Mechanisms Covalent modific

12、ations Changes in abundance of the enzymeTypes of Regulatory Mechanisms Non-covalent interactions Covalent modifications Changes in abundance of enzyme Degradation of Enzymes-ubiquitin-mediated Inducible vs Constitutive Enzymes Induction is caused by increases in rate of gene transcription. Hormones

13、 activate transcriptional factors Increase synthesis of specific mRNA Increase synthesis of specific enzymesUbiquitin pathwayE1-S-UbE2-S-UbE3substratesUbMono-ubiquitinationChange protein conformation,Localization, interactionPolyubiquitinationUbUbUbUbsubstratesProteosomeDegradationE1- Ub activating

14、enzyme(Uba)Uses ATPAMP+PPi to form thioester bond between its sulfhydryl group and the terminal carboxylate group of UBE2- Ub conjugating enzyme(Ubc):Accepts activated UBE3- Ub Ligase: Catalyzes transfer of UB from E2 to -amino group of lysine on target protein forming an isopeptide bondhttp:/www.genome.jp/kegg/pathway/map/map01100.html祝愿大家都有良好的生活习惯和健康的体格！生命科学与技术学院生命科学与技术学院医学楼主楼医学楼主楼1205Cell: 65988560,