生物化学ii(苏维恒)代谢总论.ppt

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1、BiochemistryPart IIXianghui Yu National Engineering laboratory for AIDS VaccineWhat will we learn？How to learn?Basic biochemistry:The unit of all life is the cell.Single-celled organisms:Bacteria and protozoa Multi-celled organisms:All plants and animalsHierarchy of cellular life:Cells-Tissues-Organ

2、s-Organisms-PopulationsSmall molecules of lifeWhat are the elements of living molecules?CHONPS biogenic elements:carbon,hydrogen,oxygen,nitrogen,phosphorus,sulfur Compose 99 percent of the organic matter in living cells.HydrocarbonsHCOctane=C8H18(辛烷）辛烷）(Lipids)CarbohydratesCHOGlucose=C6H12O6 (Sugars

3、)Amino acids CHON(S)Glycine=C2H5O2N (Proteins)Nucleotides CHONP AMP=C10H14N5O7P (DNA,RNA)The Four Molecules of LifeLipids：储能物能物质Sugars：能源物：能源物质Proteins：功能和：功能和结构物构物质Nucleotides：遗传物物质contents代代谢总论谢总论和生物能学和生物能学(metabolism and Bioenergetics)糖酵解（糖酵解（Glycolysis)柠柠檬酸循檬酸循环环(The Citric Acid Cycle)糖代糖代谢谢的其他途

4、径（的其他途径（Additional pathways in Carbohydrate Metabolism)电电子子传递传递与氧化磷酸化（与氧化磷酸化（Electron transport and Oxidative Phosphorylation)核酸核酸结结构和性构和性质质(Structure and properties of nucleic acids)核酸代核酸代谢谢(Nucleotide Metabolism)蛋白蛋白质质代代谢谢(Amino Acid Metabolism)脂脂类类代代谢谢(Lipid Metabolism)团队介介绍于湘晖苏维恒吴慧课课程共分程共分为为五部分五

5、部分代代谢总论谢总论和生物能学（于湘和生物能学（于湘晖晖）糖代糖代谢谢（糖酵解、糖酵解、柠柠檬酸循檬酸循环环、糖代、糖代谢谢的其他途径和的其他途径和电电子子传递传递与氧化磷酸化与氧化磷酸化）（于湘）（于湘晖晖和和马马俊峰）俊峰）核酸的核酸的结结构和核酸的代构和核酸的代谢谢（吴慧）（吴慧）脂脂类类代代谢谢（苏维苏维恒）恒）蛋白蛋白质质代代谢谢（苏维苏维恒）恒）10.1 metabolism is the Sum of Cellular ReactionsMetabolism is the entire network of chemical reactions carried out by li

6、ving cells.新新陈陈代代谢谢（metabolism）是是生生命命最最基基本本的的特特征征之之一一，泛泛指指生生物物与与周周围围环环境境进进行行物物质质交交换换、能能量量交交换换和和信信息息交交换换的的过过程程。生生物物一一方方面面不不断断地地从从周周围围环环境境中中摄摄取取能能量量和和物物质质，通通过过一一系系列列生生物物反反应应转转变变成成自自身身组组织织成成分分，即即所所谓谓同同化化作作用用（assimilation）；另另一一方方面面，将将原原有有的的组组成成成成份份经经过过一一系系列列的的生生化化反反应应，分分解解为为简简单单成成分分重重新新利利用用或或排排出出体体外外，即即

7、所所谓谓异异化化作作用用（dissimilation），通通过过上上述述过过程程不不断断地地进进行行自自我我更新。更新。合成代合成代谢与分解代与分解代谢合成代谢合成代谢 (anabolic reactions)：synthesize the molecules needed for cell maintaince,growth and reproduction.生物体内由小分子物质转化成大分子物质的过程，属同化作生物体内由小分子物质转化成大分子物质的过程，属同化作用的范畴用的范畴。分解代谢分解代谢 (catabolic reactions)：degrade molecules to liber

8、ate smaller molecules and energy.生物体内由大分子物质转变成小分子物质的过程，属异化作生物体内由大分子物质转变成小分子物质的过程，属异化作用的范畴。用的范畴。新新陈代代谢的概念及内涵的概念及内涵 小分子小分子 大分子大分子合成代合成代谢（同化作用）（同化作用）需要能量需要能量 释放能量放能量分解代分解代谢（异化作用）（异化作用）大分子大分子 小分子小分子物物质代代谢能能量量代代谢新新陈代代谢信信息息交交换Birds,beasts,plants,and soil microorganisms share with humans the same basic str

9、uctural units(cells)and the same kinds of macromolecules(DNA,RNA,proteins and lipids)made up of the same kinds of monomeric subunits(nucleotides,amino acids).They utilize the same pathways for synthesis of cellular components,share the same genetic code,and derive from the same evolutionary ancestor

10、s.Organisms change their inherited life strategies to survive in new circumstances.The result of eons of evolution is an enormous diversity of life forms,superficially very different but fundamentally related through their shared ancestry.What is the Human Genome Project?-U.S.govt.project coordinate

11、d by the Department of Energy and the National Institutes of Health,launched in 1986 by Charles DeLisi.Definition:GENOME the whole hereditary information of an organism that is encoded in the DNA.-Aims of the project:-to identify the approximate 100,000 genes in the human DNA.-determine the sequence

12、s of the 3 billion bases that make up human DNA.-store this information in databases.-develop tools for data analysis.-address the ethical,legal,and social issues that arise from genome research.Whose genome is being sequenced?-the first reference genome is a composite genome from several different

13、people.-generated from 10-20 primary samples taken from numerous anonymous donors across racial and ethnic groups.the Department of Energy and the National Institutes of HealthWatson and 3 billions Dollars1992年，Watson因为反对给人类基因申请专利退出HGP计划，Watson却认为所有与人类基因有关的知识都应该免费与全人类共享1993年，时年43岁的Francis Collins接替了

14、Watson的工作，开始领导国际基因组计划Craig Venter建议使用速度更快的“鸟枪法”测序代替链终止法。1998年，PE 公司以其刚研制成功的300台最新毛细管自动测序仪（ABI 3700）和3亿美元资金，成立了Celera Genomics公司1999年，Celera为人类的6500个基因申请专利保护。这意味着人体内将有6500条基因归Celera所有，任何人想要检测或者医药公司研发和这些基因有关疾病的新药，抑或科学家想研究这些基因都要给塞雷拉公司交钱。2000年3月14日，时任美国总统，比尔克林顿和英国首相布莱尔联合发表声明称人类基因组数据不允许专利保护，必须对所有研究者公开。从左

15、至右依次为从左至右依次为Venter、Clinton、Collins2000年6月26日，伟大的时刻终于来临，美国总统克林顿等六国领导人共同宣布人类基因组计划的草图完成。How is each area benefited specifically by the Human Genome Project?-Improvements in medicine:improved diagnosis of disease.-Microbial research:new energy sources,bio fuels.-DNA forensics:identifying potential suspe

16、cts at a crime scene.-Agriculture:more nutritious produce.-Evolution and human migration:study migration of different population groups based on female genetic inheritance.-Risk assessment:reduce the likelihood of heritable mutations.What are the implications of the Human Genome Project specifically

17、 to each of these areas?Some questions to consider:-Fairness and privacy:who should have access to your genetic information?-Psychological stigmatization:how does knowing your predisposition to disease affect an individual?-Genetic testing:should screening be done when there is no treatment availabl

18、e?Some other issues:-Reproductive issues:use of genetic information in decision making.-Clinical issues:implementation of standards and quality control measures in testing procedures.Organisms demonstrate the following common themesOrganisms or cells maintain specific internal concentrations of inor

19、ganic ions,metabolites,and enzymes.Organisms extract energy from external sources to drive energy-consuming reactions.The metabolic pathways in each organism are specified by the genes it contains in its genome.Organisms and cells interact with their environments.The cells of organisms are not stati

20、c assemblies of molecules.Many cell components are continually synthesized and degraded.E.coli has about 900 genes that encode metabolic enzymes used in intermediary metabolism and has about 130 different pathways.These genes accounts for 21%of the genes in the genome.Mycobacterium tuberculosis has

21、about 250 enzymes involved in fatty acid metabolism-five times as many as E.coli.Metabolic pathways are sequences of reactionsWithin each of the four areas of metabolism,we recognize distinct sequences of metabolic reactions,called pathway.A pathway is the biological equivalent of a synthetic or deg

22、radative scheme in organic chemistry.虽然新陈代谢包括数以千计的不同酶催化的反应，但仍可以从错综复杂的代谢网络中总结归纳成一些具有共同一些具有共同规律律的途径，并将的途径，并将这些途径称些途径称为主要代主要代谢途径途径。这些主要代谢途径在千差万别的生物界具有相当的普遍性。1.Metabolism proceeds by discrete stepsA metabolic pathway has many stepsThat begin with a specific molecule and end with a productThat are each c

23、atalyzed by a specific enzymeEnzyme 1Enzyme 2Enzyme 3ABCDReaction 1Reaction 2Reaction 3StartingmoleculeProductOne reason for multiple steps is the limitied reaction specificity of enzymes.（酶的特异性）Another reason for multiple steps in metabolic pathways is to control energy input and output.（有利于能量的摄入和释

24、放的调控）Finally,multiple steps provide opportunities to establish control points.（有利于调控）Burning vs.Metabolism生物体内的氧化过程是缓慢地，逐步将能量释放出来，其生物体内的氧化过程是缓慢地，逐步将能量释放出来，其中大部分能量转移到一些特殊的化合物中。中大部分能量转移到一些特殊的化合物中。氧化作用所放出的能量与氧化途径无关，只要最后产物相氧化作用所放出的能量与氧化途径无关，只要最后产物相同，释放出的总能量就相同。同，释放出的总能量就相同。2.Individual metabolic pathway

25、s can take different forms.A linear metabolic pathway is a series of enzyme-catalyzed reactions in which the product of one reaction is the substrate for the next reaction.A cyclic metabolic pathway is also a sequence of enzyme-catalyzed steps,but the sequence forms a closed loop,so the intermediate

26、s are regenerated.In a spiral metabolic pathway,the same set of enzymes is used repeatedly.10.2 metabolic pathways are regulatedThe flow of material through a metabolic pathway,or flux,depends not only on the supply of substrates and the removal of products but also on the activities of the enzymes

27、that catalyze individual reactions.Substrate Specificity of EnzymesThe substrateIs the reactant an enzyme acts onThe enzymeBinds to its substrate,forming an enzyme-substrate complexThe active siteIs the region on the enzyme where the substrate bindsSubstateActive siteEnzyme(a)The catalytic cycle of

28、an enzymeSubstratesProductsEnzymeEnzyme-substratecomplex 1 Substrates enter active site;enzymechanges shape so its active siteembraces the substrates(induced fit).2 Substrates held inactive site by weakinteractions,such ashydrogen bonds andionic bonds.3 Active site(and R groups ofits amino acids)can

29、 lower EAand speed up a reaction by acting as a template for substrate orientation,stressing the substrates and stabilizing the transition state,providing a favorable microenvironment,participating directly in the catalytic reaction.4 Substrates are Converted intoProducts.5 Products areReleased.6 Ac

30、tive siteIs available fortwo new substrateMole.Figure 8.17In feedback inhibition（反（反馈抑制）抑制）The end product of a metabolic pathway shuts down the pathway through inhibition of an early step,usually the first committed step.Feed-forward activation（前（前馈激活）激活）occurs when a metabolic produced early activ

31、ates an enzyme that catalyzes a reaction further down the pathway.Active siteavailableIsoleucineused up bycellFeedbackinhibitionIsoleucine binds to allosteric siteActive site of enzyme 1 no longer binds threonine;pathway is switched offInitial substrate(threonine)Threoninein active siteEnzyme 1(thre

32、oninedeaminase)Intermediate AIntermediate BIntermediate CIntermediate DEnzyme 2Enzyme 3Enzyme 4Enzyme 5End product(isoleucine)Figure 8.21新新陈代代谢的的调节 生物机体的新陈代谢是一个完整的整体，机体代谢的协调配合，关键在于它存在有精密的调节机制。代谢的调节使生物机体能适应其内、外复杂的变化环境，从而得以生存。新陈代谢的调节主要是：新陈代谢的调节主要是：1)靠酶数量和活性的调节 2)细胞中有许多由膜分割的部位，特定的代谢途径在特定的细胞部位进行。3)物质需要在

33、细胞不同的部位间运输，有时还需要在细胞间或整个机体内运输。物质运输的方向、量及速度也影响代谢。10.3 major pathways in cellsRoles of ATP and NADPH(NADH)in MetabolismATP：中心物质：中心物质两对能量携载分子：两对能量携载分子：NADH和和NAD+FADH2和和FADATP是能量代是能量代谢的中心物的中心物质 生物体直接利用的能量物质主要是生物体直接利用的能量物质主要是ATP，在，在分解代谢中，释放出的能量主要用于合成分解代谢中，释放出的能量主要用于合成ATP，在需要提供能量的反应或其它生命活动中，主要在需要提供能量的反应或其它

34、生命活动中，主要是由是由ATP水解来提供能量的，所以水解来提供能量的，所以ATP是能量代是能量代谢的中心物质。谢的中心物质。ATP不是一种能量贮存物质，而不是一种能量贮存物质，而是一种传递能量的分子，因为在一般情况下，是一种传递能量的分子，因为在一般情况下，ATP分子合成后，在分子合成后，在1分钟之内就被利用。分钟之内就被利用。辅酶和和辅酶的的递能作用能作用由营养物质的分解代谢释放出的化学能，除了通过合成ATP的途径捕获外，还有另外一种途径，就是以氢原子和电子的形式转移自由能。这种具有高能的氢原子是由脱氢反应形成的。脱氢反应产生的氢原子和电子可由辅酶或辅酶接受,形成还原型原型辅酶。当这些辅酶被

35、氧化时，能量又被释放出来。辅酶的作用：参与电子的子的传递、基、基团的的转移移等，决定了酶所催化反应的性质。NAD+/NADH，烟酰胺腺嘌呤二核苷酸，烟酰胺腺嘌呤二核苷酸（氧化（氧化/还原）还原）NADP+/NADPH，烟酰胺腺嘌呤二核苷酸磷酸，烟酰胺腺嘌呤二核苷酸磷酸（氧化（氧化/还原）。还原）。维生素生素B3（也称（也称维生素生素pp、或烟、或烟酰胺胺 nicotinamide）（1 1）结构结构 维生素维生素B3是吡啶的衍生物是吡啶的衍生物 吡啶吡啶-3-羧酸羧酸 nicotinic acid（烟酸）（烟酸）吡啶吡啶-3-酰胺酰胺 Nicotinamide（烟酰胺）（烟酰胺）（2）功能）功

36、能 B3是是NAD和和NADP的组成成分，的组成成分，NAD和和NADP是许多脱氢酶的辅酶，参与递氢。是许多脱氢酶的辅酶，参与递氢。维生素生素B2的衍生物的衍生物辅酶辅酶A A在能量代谢中的作用在能量代谢中的作用 乙乙酰CoA中中有有一一个个高高能能的的硫硫酯键，这也也可可以以看看成成是是酰基基的的一一种种活活化化形形式式。ATP的的酸酸酐键水水解解时释放放出出30.54 kJ/mol的的自自由由能能，而而乙乙酰CoA的的硫硫酯键水水解解时释放放出出31.38 kJ/mol的的自自由由能。能。B5是是CoA的组成成分，的组成成分，CoA是生是生物体内转酰基酶的辅酶（主要作物体内转酰基酶的辅酶（

37、主要作为转乙酰基酶的辅酶），参与转为转乙酰基酶的辅酶），参与转酰基作用。酰基作用。10.4 Compartmentation and interorgan metabolism新新陈代代谢小小结1.1.代代谢的功能概括的功能概括为5 5个方面：个方面：1.从周围环境中获得营养物质。2.将外界引入的营养物质转变为自身需要的结构元件，即大分子的组成前体。3.将结构元件装配成自身的大分子4.合成或降解执行生物体特殊功能所需的生物分子。5.提供生命活动所需的一切能量。2.Anabolism and Catabolism3.Properties of Metabolic PathwaysIrrevers

38、ible(overall):reversibility of individual stepsSeparate Anabolic and Catabolic PathwaysFirst Committed(Exergonic)Step:others close to equilibriumRegulation(usually first committed step):often rate-limiting4.Features of Metabolic PathwaysA B C D E(1)Sequences and Energetics(2)Enzymes and Mechanisms(3)Control Mechanisms(Regulation)(4)Compartmentation