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小第708行：
第708行： − + 第718行：
第718行： − 生命有机体必须遵守热力学定律，该定律描述了热量和功的传递。热力学第二定律指出，在任何封闭系统中，熵的量(无序)不会减少。尽管生物体惊人的复杂性似乎与这一定律相矛盾，但生命是可能它们的环境交换物质和能量的，因为所有生物体都是开放的系统。因此，生命系统不是处于平衡状态，而是耗散系统，通过引起其环境熵的较大增加来维持其高度复杂的状态。细胞的新陈代谢通过耦合分解代谢的自发过程和合成代谢的非自发过程来实现这一点。从热力学的角度来看，新陈代谢通过制造混乱来维持秩序。+ 第730行：
第730行： − 由于大多数生物体的环境是不断变化的，因此必须对新陈代谢的反应进行精细的调节，以维持细胞内一套恒定的条件，这种条件称为稳态。代谢调节也使生物体能够对信号作出反应，并与环境积极互动。有两个密切相关的概念对于理解代谢途径是如何被控制的很重要。首先，途径中酶的调节是指其活性如何在信号的作用下增加和减少。其次，这种酶所施加的控制是指它的活性的这些变化对通路的总体速率（通过通路的通量）的影响。例如，一种酶可能表现出很大的活性变化(即它是高度受控的)，但如果这些变化对某一代谢途径的通量影响不大，那么这种酶就不参与该途径的控制。+ 第742行：
第742行： − 新陈代谢调节有多个层次。在内在调节中，代谢途径自我调节，以应对底物或产物水平的变化；例如，产物数量的减少可以增加通过该途径的通量以进行补偿。外在控制是指多细胞生物体中的一个细胞根据来自其他细胞的信号改变其代谢。这些信号通常以水溶性信使的形式出现，如激素和生长因子，并被细胞表面的特定受体检测到。然后，这些信号通过第二信使系统在细胞内传递，该系统通常涉及蛋白质的磷酸化。+ 第748行：
第748行： − 一个非常好理解的外在控制的例子是通过激素胰岛素对葡萄糖代谢的调节。胰岛素是在血糖水平上升时产生的。胰岛素与细胞上的胰岛素受体结合，然后激活一连串的蛋白激酶，使细胞吸收葡萄糖，并将其转化为储存分子，如脂肪酸和糖原。糖原的新陈代谢受到分解糖原的磷酸化酶和制造糖原的糖原合成酶的活性控制。这些酶的调节方式是相互的，磷酸化抑制糖原合成酶，但激活磷酸化酶。胰岛素通过激活蛋白磷酸酶，使这些酶的磷酸化程度降低，从而引起糖原合成。+ 第760行：
第760行： − 进化树显示了来自所有三个生命领域的生物体的共同祖先。细菌呈蓝色，真核生物呈红色，古菌呈绿色。树木周围显示了一些门的相对位置。+ 第766行：
第766行： − 上述代谢的主要途径，如糖酵解和柠檬酸循环，存在于生物的所有三个领域中，并存在于最后的普遍共同祖先中。这种普遍的祖先细胞是原核生物，可能是一种具有广泛的氨基酸、核苷酸、碳水化合物和脂质代谢的产烷生物。在后来的进化过程中，这些古老的途径得以保留，可能是因为这些反应对它们特定的代谢问题提供了最佳解决方案，这些途径如糖酵解和三羧酸循环以最少的步骤高效地产生它们的最终产物。最初的基于酶的代谢途径可能是嘌呤核苷酸代谢的一部分，而之前的代谢途径是古代RNA世界的一部分。+ 第772行：
第772行： − 有人提出了许多模型来描述新的代谢途径的演变机制。其中包括将新的酶连续添加到一个短的祖先途径，整个途径的复制和分化，以及将原有的酶补充并将其组装成一个新的反应途径。这些机制的相对重要性尚不清楚，但基因组研究表明，一条途径中的酶很可能有共同的祖先，这表明许多途径是以逐步进化的方式，从途径中预先存在的步骤中创造了新的功能。另一种模型来自于追踪代谢网络中蛋白质结构进化的研究，这表明酶在不同的代谢途径中普遍被征用，借用酶来执行相似的功能(在 MANET 数据库中显而易见)这些征用过程导致了进化酶的嵌合。第三种可能性是，新陈代谢的某些部分可能作为“模块”存在，可以在不同的途径中重复使用，并对不同的分子执行类似的功能。+ 第778行：
第778行： − 除了新的代谢途径的进化，进化也会导致代谢功能的丧失。例如，在某些寄生物中，并非生存必需的代谢过程丢失了，而预先形成的氨基酸、核苷酸和碳水化合物可能会从寄主那里被清除。在内共生生物体中也可以看到类似的代谢能力下降。+ 第790行：
第790行： − + − + − 传统上，新陈代谢的研究采用还原法，侧重于单一的新陈代谢途径。特别有价值的是在整个有机体、组织和细胞水平上使用放射性示踪剂，通过确定放射性标记的中间物和产品，确定从前体到最终产品的路径。然后可以纯化催化这些化学反应的酶，并研究其动力学和对抑制剂的反应。一个平行的方法是识别细胞或组织中的小分子；这些分子的完整集合被称为代谢组。总的来说，这些研究可以很好地了解简单代谢途径的结构和功能，但当应用于更复杂的系统，如一个完整细胞的代谢时，这些研究是不够的。+ 第803行：
第803行： − 右边的图显示了43种蛋白质和40种代谢物之间的相互作用，由此可以看出细胞中包含数千种不同酶的代谢网络的复杂性: 基因组序列提供了包含26.500个基因的列表。然而，现在有可能利用这些基因组数据来重建完整的生化反应网络，并产生更全面的数学模型来解释和预测它们的行为。这些模型在用于整合通过经典方法获得的途径和代谢物数据与蛋白质组学和DNA微阵列研究的基因表达数据时特别强大。利用这些技术，现在已经产生了一个人类代谢的模型，这将指导未来的药物发现和生化研究。这些模型现在被用于网络分析，将人类疾病划分为具有共同蛋白质或代谢物的群体。+ 第809行：
第809行： − 细菌代谢网络是蝴蝶结结构的一个突出例子，这种架构能够输入多种营养物质，并利用相对较少的中间通用货币生产出大量的产品和复杂的大分子。+ 第817行：
第817行： − 这些信息的一个主要技术应用是代谢工程学。在这里，酵母、植物或细菌等生物体都经过基因改造，使它们在生物技术方面更有用处，并有助于生产抗生素等药物或工业化学品，例如1,3- 丙二醇和莽草酸。这些基因改造通常旨在减少生产产品所使用的能源，提高产量和减少废物的产生。+ 第829行：
第829行： − + 第851行：
第851行： − + 第859行：
第859行： − 新陈代谢的科学研究历史跨越了几个世纪，从早期研究中对整个动物的研究，到现代生物化学中对单个代谢反应的研究。 人类新陈代谢的第一个对照实验是由 圣托里奥·桑托里奥 Santorio Santorio于1614年在他的著作《静态医学》中发表的。他描述了自己在进食、睡觉、工作、性交、禁食、饮水和排泄前后的体重。他发现他摄入的大部分食物都是通过他所谓的“无知觉的汗液”流失的。+ 第865行：
第865行： − + 第871行：
第871行： − 在这些早期的研究中，这些新陈代谢过程的机制还没有确定，人们认为一种生命力是生命组织的活力。19世纪，路易-巴斯德Louis Pasteur 在研究酵母菌将糖发酵成酒精时，得出结论：发酵是由酵母细胞内的物质催化的，他称之为 "发酵物"。他写道："酒精发酵是与酵母细胞的生命和组织有关的行为，而不是与细胞的死亡或腐烂有关"。这一发现连同1828年弗里德里希-沃勒Friedrich Wöhler 发表的一篇关于尿素化学合成的论文，并且因为是第一个完全由无机前体制备的有机化合物而引人注目。这证明了在细胞中发现的有机化合物和化学反应与化学的任何其他部分在原理上没有什么不同。+ 第878行：
第878行： − +
无编辑摘要
对于好氧生物来说，一个相关的问题是氧化应激。这个过程包括氧化磷酸化和蛋白质折叠时二硫键的形成，它产生了活性氧类（如过氧化氢）。这些破坏性的氧化剂被抗氧化代谢物（如谷胱甘肽和酶）和酶（如过氧化氢酶和过氧化物酶）去除。
对于好氧生物来说，一个相关的问题是氧化应激。这个过程包括氧化磷酸化和蛋白质折叠时二硫键的形成，它产生了活性氧类（如过氧化氢）。这些破坏性的氧化剂被抗氧化代谢物（如谷胱甘肽和酶）和酶（如过氧化氢酶和过氧化物酶）去除。
==Thermodynamics of living organisms==【Fernando标记】
==Thermodynamics of living organisms==
生命有机体的热力学
生命有机体的热力学
{{further|Biological thermodynamics}}
{{further|Biological thermodynamics}}
Living organisms must obey the laws of thermodynamics, which describe the transfer of heat and work. The second law of thermodynamics states that in any closed system, the amount of entropy (disorder) cannot decrease. Although living organisms' amazing complexity appears to contradict this law, life is possible as all organisms are open systems that exchange matter and energy with their surroundings. Thus living systems are not in equilibrium, but instead are dissipative systems that maintain their state of high complexity by causing a larger increase in the entropy of their environments. The metabolism of a cell achieves this by coupling the spontaneous processes of catabolism to the non-spontaneous processes of anabolism. In thermodynamic terms, metabolism maintains order by creating disorder.
Living organisms must obey the laws of thermodynamics, which describe the transfer of heat and work. The second law of thermodynamics states that in any closed system, the amount of entropy (disorder) cannot decrease. Although living organisms' amazing complexity appears to contradict this law, life is possible as all organisms are open systems that exchange matter and energy with their surroundings. Thus living systems are not in equilibrium, but instead are dissipative systems that maintain their state of high complexity by causing a larger increase in the entropy of their environments. The metabolism of a cell achieves this by coupling the spontaneous processes of catabolism to the non-spontaneous processes of anabolism. In thermodynamic terms, metabolism maintains order by creating disorder.
生命有机体一定会遵守热力学定律，该定律描述了热量和功的传递。热力学第二定律指出，在任何封闭系统中，熵的总量（混乱度）不会减少。尽管生物体惊人的复杂性似乎与这一定律相矛盾，但生命是可能的，因为它们是与环境交换物质和能量的开放系统。也就是说，生命系统并不处于平衡状态，而是耗散系统，它通过大量增加环境熵来维持其高度复杂的状态。细胞的新陈代谢通过将分解代谢的自发过程和合成代谢的非自发过程进行耦合来实现这一点。从热力学的角度来看，新陈代谢通过制造混乱来维持秩序。
==Regulation and control==
==Regulation and control==
As the environments of most organisms are constantly changing, the reactions of metabolism must be finely regulated to maintain a constant set of conditions within cells, a condition called homeostasis. Metabolic regulation also allows organisms to respond to signals and interact actively with their environments. Two closely linked concepts are important for understanding how metabolic pathways are controlled. Firstly, the regulation of an enzyme in a pathway is how its activity is increased and decreased in response to signals. Secondly, the control exerted by this enzyme is the effect that these changes in its activity have on the overall rate of the pathway (the flux through the pathway). For example, an enzyme may show large changes in activity (i.e. it is highly regulated) but if these changes have little effect on the flux of a metabolic pathway, then this enzyme is not involved in the control of the pathway.
As the environments of most organisms are constantly changing, the reactions of metabolism must be finely regulated to maintain a constant set of conditions within cells, a condition called homeostasis. Metabolic regulation also allows organisms to respond to signals and interact actively with their environments. Two closely linked concepts are important for understanding how metabolic pathways are controlled. Firstly, the regulation of an enzyme in a pathway is how its activity is increased and decreased in response to signals. Secondly, the control exerted by this enzyme is the effect that these changes in its activity have on the overall rate of the pathway (the flux through the pathway). For example, an enzyme may show large changes in activity (i.e. it is highly regulated) but if these changes have little effect on the flux of a metabolic pathway, then this enzyme is not involved in the control of the pathway.
由于大多数生物体的环境是不断变化的，因此它们必须对新陈代谢的反应进行精细的调节，以维持细胞内一系列恒定的条件，这种条件称为稳态。代谢调节也使生物体能够对信号作出反应，并与环境积极互动。有两个密切相关的概念对于理解“代谢途径是如何被控制的”十分重要。首先，途径中酶的调节是指其活性如何响应信号从而增加和减少。其次，这种酶所施加的控制是指它的活性变化对通路的总体速率（通过通路的通量）的影响。例如，一种酶可能表现出很大的活性变化(即它是高度受控的)，但如果这些变化对某一代谢途径的通量影响不大，那么这种酶就不参与该途径的控制。
[[File:Insulin glucose metabolism ZP.svg|thumb|right|upright=1.35|'''Effect of insulin on glucose uptake and metabolism.''' Insulin binds to its receptor (1), which in turn starts many protein activation cascades (2). These include: translocation of Glut-4 transporter to the [[plasma membrane]] and influx of glucose (3), [[glycogen]] synthesis (4), [[glycolysis]] (5) and [[fatty acid]] synthesis (6).]]
[[File:Insulin glucose metabolism ZP.svg|thumb|right|upright=1.35|'''Effect of insulin on glucose uptake and metabolism.''' Insulin binds to its receptor (1), which in turn starts many protein activation cascades (2). These include: translocation of Glut-4 transporter to the [[plasma membrane]] and influx of glucose (3), [[glycogen]] synthesis (4), [[glycolysis]] (5) and [[fatty acid]] synthesis (6).]]
There are multiple levels of metabolic regulation. In intrinsic regulation, the metabolic pathway self-regulates to respond to changes in the levels of substrates or products; for example, a decrease in the amount of product can increase the flux through the pathway to compensate. Extrinsic control involves a cell in a multicellular organism changing its metabolism in response to signals from other cells. These signals are usually in the form of water soluble messengers such as hormones and growth factors and are detected by specific receptors on the cell surface. These signals are then transmitted inside the cell by second messenger systems that often involved the phosphorylation of proteins.
There are multiple levels of metabolic regulation. In intrinsic regulation, the metabolic pathway self-regulates to respond to changes in the levels of substrates or products; for example, a decrease in the amount of product can increase the flux through the pathway to compensate. Extrinsic control involves a cell in a multicellular organism changing its metabolism in response to signals from other cells. These signals are usually in the form of water soluble messengers such as hormones and growth factors and are detected by specific receptors on the cell surface. These signals are then transmitted inside the cell by second messenger systems that often involved the phosphorylation of proteins.
新陈代谢调节有多个层次。在内在调节中，代谢途径自我调节，以应对底物或产物数量的变化；例如，产物数量的减少可以增加通过该途径的通量以进行补偿。外在控制是指多细胞生物体中的一个细胞根据来自其他细胞的信号改变其代谢。这些信号通常以水溶性信使的形式出现（如激素和生长因子），并被细胞表面的特定受体检测到。然后，这些信号通过第二信使系统在细胞内传递，该系统通常涉及蛋白质的磷酸化。
A very well understood example of extrinsic control is the regulation of glucose metabolism by the hormone [[insulin]].<ref>{{cite journal | vauthors = Lienhard GE, Slot JW, James DE, Mueckler MM | title = How cells absorb glucose | journal = Scientific American | volume = 266 | issue = 1 | pages = 86–91 | date = January 1992 | pmid = 1734513 | doi = 10.1038/scientificamerican0192-86 | bibcode = 1992SciAm.266a..86L }}</ref> Insulin is produced in response to rises in [[blood sugar|blood glucose levels]]. Binding of the hormone to [[insulin receptor]]s on cells then activates a cascade of [[protein kinase]]s that cause the cells to take up glucose and convert it into storage molecules such as fatty acids and [[glycogen]].<ref>{{cite journal | vauthors = Roach PJ | title = Glycogen and its metabolism | journal = Current Molecular Medicine | volume = 2 | issue = 2 | pages = 101–20 | date = March 2002 | pmid = 11949930 | doi = 10.2174/1566524024605761 }}</ref> The metabolism of glycogen is controlled by activity of [[phosphorylase]], the enzyme that breaks down glycogen, and [[glycogen synthase]], the enzyme that makes it. These enzymes are regulated in a reciprocal fashion, with phosphorylation inhibiting glycogen synthase, but activating phosphorylase. Insulin causes glycogen synthesis by activating [[phosphatase|protein phosphatases]] and producing a decrease in the phosphorylation of these enzymes.<ref>{{cite journal | vauthors = Newgard CB, Brady MJ, O'Doherty RM, Saltiel AR | title = Organizing glucose disposal: emerging roles of the glycogen targeting subunits of protein phosphatase-1 | journal = Diabetes | volume = 49 | issue = 12 | pages = 1967–77 | date = December 2000 | pmid = 11117996 | doi = 10.2337/diabetes.49.12.1967 | url = http://diabetes.diabetesjournals.org/cgi/reprint/49/12/1967.pdf }}</ref>
A very well understood example of extrinsic control is the regulation of glucose metabolism by the hormone [[insulin]].<ref>{{cite journal | vauthors = Lienhard GE, Slot JW, James DE, Mueckler MM | title = How cells absorb glucose | journal = Scientific American | volume = 266 | issue = 1 | pages = 86–91 | date = January 1992 | pmid = 1734513 | doi = 10.1038/scientificamerican0192-86 | bibcode = 1992SciAm.266a..86L }}</ref> Insulin is produced in response to rises in [[blood sugar|blood glucose levels]]. Binding of the hormone to [[insulin receptor]]s on cells then activates a cascade of [[protein kinase]]s that cause the cells to take up glucose and convert it into storage molecules such as fatty acids and [[glycogen]].<ref>{{cite journal | vauthors = Roach PJ | title = Glycogen and its metabolism | journal = Current Molecular Medicine | volume = 2 | issue = 2 | pages = 101–20 | date = March 2002 | pmid = 11949930 | doi = 10.2174/1566524024605761 }}</ref> The metabolism of glycogen is controlled by activity of [[phosphorylase]], the enzyme that breaks down glycogen, and [[glycogen synthase]], the enzyme that makes it. These enzymes are regulated in a reciprocal fashion, with phosphorylation inhibiting glycogen synthase, but activating phosphorylase. Insulin causes glycogen synthesis by activating [[phosphatase|protein phosphatases]] and producing a decrease in the phosphorylation of these enzymes.<ref>{{cite journal | vauthors = Newgard CB, Brady MJ, O'Doherty RM, Saltiel AR | title = Organizing glucose disposal: emerging roles of the glycogen targeting subunits of protein phosphatase-1 | journal = Diabetes | volume = 49 | issue = 12 | pages = 1967–77 | date = December 2000 | pmid = 11117996 | doi = 10.2337/diabetes.49.12.1967 | url = http://diabetes.diabetesjournals.org/cgi/reprint/49/12/1967.pdf }}</ref>
A very well understood example of extrinsic control is the regulation of glucose metabolism by the hormone insulin. Insulin is produced in response to rises in blood glucose levels. Binding of the hormone to insulin receptors on cells then activates a cascade of protein kinases that cause the cells to take up glucose and convert it into storage molecules such as fatty acids and glycogen. The metabolism of glycogen is controlled by activity of phosphorylase, the enzyme that breaks down glycogen, and glycogen synthase, the enzyme that makes it. These enzymes are regulated in a reciprocal fashion, with phosphorylation inhibiting glycogen synthase, but activating phosphorylase. Insulin causes glycogen synthesis by activating protein phosphatases and producing a decrease in the phosphorylation of these enzymes.
A very well understood example of extrinsic control is the regulation of glucose metabolism by the hormone insulin. Insulin is produced in response to rises in blood glucose levels. Binding of the hormone to insulin receptors on cells then activates a cascade of protein kinases that cause the cells to take up glucose and convert it into storage molecules such as fatty acids and glycogen. The metabolism of glycogen is controlled by activity of phosphorylase, the enzyme that breaks down glycogen, and glycogen synthase, the enzyme that makes it. These enzymes are regulated in a reciprocal fashion, with phosphorylation inhibiting glycogen synthase, but activating phosphorylase. Insulin causes glycogen synthesis by activating protein phosphatases and producing a decrease in the phosphorylation of these enzymes.
一个非常好理解的外在控制的例子是激素胰岛素对葡萄糖代谢的调节。胰岛素是在血糖升高时产生的。胰岛素与细胞上的胰岛素受体结合，然后激活一连串的蛋白激酶，使细胞吸收葡萄糖，并将其转化为储存分子（如脂肪酸和糖原）。糖原的新陈代谢受到分解糖原的磷酸化酶和制造糖原的糖原合成酶的活性控制。这些酶的调节方式是相互的，磷酸化作用抑制糖原合成酶，但激活磷酸化酶。胰岛素通过激活蛋白磷酸酶使这些酶的磷酸化程度降低，从而触发糖原合成。
==Evolution==
==Evolution==
Evolutionary tree showing the common ancestry of organisms from all three domains of life. Bacteria are colored blue, eukaryotes red, and archaea green. Relative positions of some of the phyla included are shown around the tree.]]
Evolutionary tree showing the common ancestry of organisms from all three domains of life. Bacteria are colored blue, eukaryotes red, and archaea green. Relative positions of some of the phyla included are shown around the tree.]]
演化树显示了来自全部三个生命领域的生物体的共同祖先。细菌呈蓝色，真核生物呈红色，古菌呈绿色。树木周围显示了一些门的相对位置。
The central pathways of metabolism described above, such as glycolysis and the citric acid cycle, are present in all [[Three-domain system|three domains]] of living things and were present in the [[last universal common ancestor]].<ref name=SmithE/><ref>{{cite journal | vauthors = Romano AH, Conway T | title = Evolution of carbohydrate metabolic pathways | journal = Research in Microbiology | volume = 147 | issue = 6–7 | pages = 448–55 | year = 1996 | pmid = 9084754 | doi = 10.1016/0923-2508(96)83998-2 }}</ref> This universal ancestral cell was [[prokaryote|prokaryotic]] and probably a [[methanogen]] that had extensive amino acid, nucleotide, carbohydrate and lipid metabolism.<ref>{{cite book |author=Koch A |title=How did bacteria come to be? |journal=Adv Microb Physiol |volume=40 |pages=353–99 |year=1998 |pmid=9889982 |doi=10.1016/S0065-2911(08)60135-6 |series=Advances in Microbial Physiology |isbn=978-0-12-027740-7}}</ref><ref>{{cite journal | vauthors = Ouzounis C, Kyrpides N | title = The emergence of major cellular processes in evolution | journal = FEBS Letters | volume = 390 | issue = 2 | pages = 119–23 | date = July 1996 | pmid = 8706840 | doi = 10.1016/0014-5793(96)00631-X | s2cid = 39128865 }}</ref> The retention of these ancient pathways during later [[evolution]] may be the result of these reactions having been an optimal solution to their particular metabolic problems, with pathways such as glycolysis and the citric acid cycle producing their end products highly efficiently and in a minimal number of steps.<ref name=Ebenhoh/><ref name=Cascante/> The first pathways of enzyme-based metabolism may have been parts of [[purine]] nucleotide metabolism, while previous metabolic pathways were a part of the ancient [[RNA world hypothesis|RNA world]].<ref>{{cite journal | vauthors = Caetano-Anollés G, Kim HS, Mittenthal JE | title = The origin of modern metabolic networks inferred from phylogenomic analysis of protein architecture | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 22 | pages = 9358–63 | date = May 2007 | pmid = 17517598 | pmc = 1890499 | doi = 10.1073/pnas.0701214104 | bibcode = 2007PNAS..104.9358C }}</ref>
The central pathways of metabolism described above, such as glycolysis and the citric acid cycle, are present in all [[Three-domain system|three domains]] of living things and were present in the [[last universal common ancestor]].<ref name=SmithE/><ref>{{cite journal | vauthors = Romano AH, Conway T | title = Evolution of carbohydrate metabolic pathways | journal = Research in Microbiology | volume = 147 | issue = 6–7 | pages = 448–55 | year = 1996 | pmid = 9084754 | doi = 10.1016/0923-2508(96)83998-2 }}</ref> This universal ancestral cell was [[prokaryote|prokaryotic]] and probably a [[methanogen]] that had extensive amino acid, nucleotide, carbohydrate and lipid metabolism.<ref>{{cite book |author=Koch A |title=How did bacteria come to be? |journal=Adv Microb Physiol |volume=40 |pages=353–99 |year=1998 |pmid=9889982 |doi=10.1016/S0065-2911(08)60135-6 |series=Advances in Microbial Physiology |isbn=978-0-12-027740-7}}</ref><ref>{{cite journal | vauthors = Ouzounis C, Kyrpides N | title = The emergence of major cellular processes in evolution | journal = FEBS Letters | volume = 390 | issue = 2 | pages = 119–23 | date = July 1996 | pmid = 8706840 | doi = 10.1016/0014-5793(96)00631-X | s2cid = 39128865 }}</ref> The retention of these ancient pathways during later [[evolution]] may be the result of these reactions having been an optimal solution to their particular metabolic problems, with pathways such as glycolysis and the citric acid cycle producing their end products highly efficiently and in a minimal number of steps.<ref name=Ebenhoh/><ref name=Cascante/> The first pathways of enzyme-based metabolism may have been parts of [[purine]] nucleotide metabolism, while previous metabolic pathways were a part of the ancient [[RNA world hypothesis|RNA world]].<ref>{{cite journal | vauthors = Caetano-Anollés G, Kim HS, Mittenthal JE | title = The origin of modern metabolic networks inferred from phylogenomic analysis of protein architecture | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 22 | pages = 9358–63 | date = May 2007 | pmid = 17517598 | pmc = 1890499 | doi = 10.1073/pnas.0701214104 | bibcode = 2007PNAS..104.9358C }}</ref>
The central pathways of metabolism described above, such as glycolysis and the citric acid cycle, are present in all three domains of living things and were present in the last universal common ancestor.This universal ancestral cell was prokaryotic and probably a methanogen that had extensive amino acid, nucleotide, carbohydrate and lipid metabolism.The retention of these ancient pathways during later evolution may be the result of these reactions having been an optimal solution to their particular metabolic problems, with pathways such as glycolysis and the citric acid cycle producing their end products highly efficiently and in a minimal number of steps.The first pathways of enzyme-based metabolism may have been parts of purine nucleotide metabolism, while previous metabolic pathways were a part of the ancient RNA world.
The central pathways of metabolism described above, such as glycolysis and the citric acid cycle, are present in all three domains of living things and were present in the last universal common ancestor.This universal ancestral cell was prokaryotic and probably a methanogen that had extensive amino acid, nucleotide, carbohydrate and lipid metabolism.The retention of these ancient pathways during later evolution may be the result of these reactions having been an optimal solution to their particular metabolic problems, with pathways such as glycolysis and the citric acid cycle producing their end products highly efficiently and in a minimal number of steps.The first pathways of enzyme-based metabolism may have been parts of purine nucleotide metabolism, while previous metabolic pathways were a part of the ancient RNA world.
上述代谢的主要途径，如糖酵解和柠檬酸循环，存在于生物的全部三个领域中，并存在于最后的普遍共同祖先中。这种普遍的祖先细胞是原核生物，也许是一种具有广泛的氨基酸、核苷酸、碳水化合物和脂质代谢的产烷菌。在后来的进化过程中，这些古老的途径之所以得以保留，可能是因为这些反应为它们特定的代谢问题提供了最佳解决方案，这些途径（如糖酵解和三羧酸循环）以最少的步骤高效地产生它们的最终产物。最初的基于酶的代谢途径可能是嘌呤核苷酸代谢的一部分，而之前的代谢途径是远古RNA界的一部分。
Many models have been proposed to describe the mechanisms by which novel metabolic pathways evolve. These include the sequential addition of novel enzymes to a short ancestral pathway, the duplication and then divergence of entire pathways as well as the recruitment of pre-existing enzymes and their assembly into a novel reaction pathway.<ref>{{cite journal | vauthors = Schmidt S, Sunyaev S, Bork P, Dandekar T | title = Metabolites: a helping hand for pathway evolution? | journal = Trends in Biochemical Sciences | volume = 28 | issue = 6 | pages = 336–41 | date = June 2003 | pmid = 12826406 | doi = 10.1016/S0968-0004(03)00114-2 }}</ref> The relative importance of these mechanisms is unclear, but genomic studies have shown that enzymes in a pathway are likely to have a shared ancestry, suggesting that many pathways have evolved in a step-by-step fashion with novel functions created from pre-existing steps in the pathway.<ref>{{cite journal | vauthors = Light S, Kraulis P | title = Network analysis of metabolic enzyme evolution in Escherichia coli | journal = BMC Bioinformatics | volume = 5 | pages = 15 | date = February 2004 | pmid = 15113413 | pmc = 394313 | doi = 10.1186/1471-2105-5-15 }} {{cite journal | vauthors = Alves R, Chaleil RA, Sternberg MJ | title = Evolution of enzymes in metabolism: a network perspective | journal = Journal of Molecular Biology | volume = 320 | issue = 4 | pages = 751–70 | date = July 2002 | pmid = 12095253 | doi = 10.1016/S0022-2836(02)00546-6 }}</ref> An alternative model comes from studies that trace the evolution of proteins' structures in metabolic networks, this has suggested that enzymes are pervasively recruited, borrowing enzymes to perform similar functions in different metabolic pathways (evident in the [[MANET database]])<ref>{{cite journal | vauthors = Kim HS, Mittenthal JE, Caetano-Anollés G | title = MANET: tracing evolution of protein architecture in metabolic networks | journal = BMC Bioinformatics | volume = 7 | pages = 351 | date = July 2006 | pmid = 16854231 | pmc = 1559654 | doi = 10.1186/1471-2105-7-351 }}</ref> These recruitment processes result in an evolutionary enzymatic mosaic.<ref>{{cite journal | vauthors = Teichmann SA, Rison SC, Thornton JM, Riley M, Gough J, Chothia C | title = Small-molecule metabolism: an enzyme mosaic | journal = Trends in Biotechnology | volume = 19 | issue = 12 | pages = 482–6 | date = December 2001 | pmid = 11711174 | doi = 10.1016/S0167-7799(01)01813-3 }}</ref> A third possibility is that some parts of metabolism might exist as "modules" that can be reused in different pathways and perform similar functions on different molecules.<ref>{{cite journal | vauthors = Spirin V, Gelfand MS, Mironov AA, Mirny LA | title = A metabolic network in the evolutionary context: multiscale structure and modularity | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 23 | pages = 8774–9 | date = June 2006 | pmid = 16731630 | pmc = 1482654 | doi = 10.1073/pnas.0510258103 | bibcode = 2006PNAS..103.8774S }}</ref>
Many models have been proposed to describe the mechanisms by which novel metabolic pathways evolve. These include the sequential addition of novel enzymes to a short ancestral pathway, the duplication and then divergence of entire pathways as well as the recruitment of pre-existing enzymes and their assembly into a novel reaction pathway.<ref>{{cite journal | vauthors = Schmidt S, Sunyaev S, Bork P, Dandekar T | title = Metabolites: a helping hand for pathway evolution? | journal = Trends in Biochemical Sciences | volume = 28 | issue = 6 | pages = 336–41 | date = June 2003 | pmid = 12826406 | doi = 10.1016/S0968-0004(03)00114-2 }}</ref> The relative importance of these mechanisms is unclear, but genomic studies have shown that enzymes in a pathway are likely to have a shared ancestry, suggesting that many pathways have evolved in a step-by-step fashion with novel functions created from pre-existing steps in the pathway.<ref>{{cite journal | vauthors = Light S, Kraulis P | title = Network analysis of metabolic enzyme evolution in Escherichia coli | journal = BMC Bioinformatics | volume = 5 | pages = 15 | date = February 2004 | pmid = 15113413 | pmc = 394313 | doi = 10.1186/1471-2105-5-15 }} {{cite journal | vauthors = Alves R, Chaleil RA, Sternberg MJ | title = Evolution of enzymes in metabolism: a network perspective | journal = Journal of Molecular Biology | volume = 320 | issue = 4 | pages = 751–70 | date = July 2002 | pmid = 12095253 | doi = 10.1016/S0022-2836(02)00546-6 }}</ref> An alternative model comes from studies that trace the evolution of proteins' structures in metabolic networks, this has suggested that enzymes are pervasively recruited, borrowing enzymes to perform similar functions in different metabolic pathways (evident in the [[MANET database]])<ref>{{cite journal | vauthors = Kim HS, Mittenthal JE, Caetano-Anollés G | title = MANET: tracing evolution of protein architecture in metabolic networks | journal = BMC Bioinformatics | volume = 7 | pages = 351 | date = July 2006 | pmid = 16854231 | pmc = 1559654 | doi = 10.1186/1471-2105-7-351 }}</ref> These recruitment processes result in an evolutionary enzymatic mosaic.<ref>{{cite journal | vauthors = Teichmann SA, Rison SC, Thornton JM, Riley M, Gough J, Chothia C | title = Small-molecule metabolism: an enzyme mosaic | journal = Trends in Biotechnology | volume = 19 | issue = 12 | pages = 482–6 | date = December 2001 | pmid = 11711174 | doi = 10.1016/S0167-7799(01)01813-3 }}</ref> A third possibility is that some parts of metabolism might exist as "modules" that can be reused in different pathways and perform similar functions on different molecules.<ref>{{cite journal | vauthors = Spirin V, Gelfand MS, Mironov AA, Mirny LA | title = A metabolic network in the evolutionary context: multiscale structure and modularity | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 23 | pages = 8774–9 | date = June 2006 | pmid = 16731630 | pmc = 1482654 | doi = 10.1073/pnas.0510258103 | bibcode = 2006PNAS..103.8774S }}</ref>
Many models have been proposed to describe the mechanisms by which novel metabolic pathways evolve. These include the sequential addition of novel enzymes to a short ancestral pathway, the duplication and then divergence of entire pathways as well as the recruitment of pre-existing enzymes and their assembly into a novel reaction pathway. The relative importance of these mechanisms is unclear, but genomic studies have shown that enzymes in a pathway are likely to have a shared ancestry, suggesting that many pathways have evolved in a step-by-step fashion with novel functions created from pre-existing steps in the pathway. An alternative model comes from studies that trace the evolution of proteins' structures in metabolic networks, this has suggested that enzymes are pervasively recruited, borrowing enzymes to perform similar functions in different metabolic pathways (evident in the MANET database) These recruitment processes result in an evolutionary enzymatic mosaic. A third possibility is that some parts of metabolism might exist as "modules" that can be reused in different pathways and perform similar functions on different molecules.
Many models have been proposed to describe the mechanisms by which novel metabolic pathways evolve. These include the sequential addition of novel enzymes to a short ancestral pathway, the duplication and then divergence of entire pathways as well as the recruitment of pre-existing enzymes and their assembly into a novel reaction pathway. The relative importance of these mechanisms is unclear, but genomic studies have shown that enzymes in a pathway are likely to have a shared ancestry, suggesting that many pathways have evolved in a step-by-step fashion with novel functions created from pre-existing steps in the pathway. An alternative model comes from studies that trace the evolution of proteins' structures in metabolic networks, this has suggested that enzymes are pervasively recruited, borrowing enzymes to perform similar functions in different metabolic pathways (evident in the MANET database) These recruitment processes result in an evolutionary enzymatic mosaic. A third possibility is that some parts of metabolism might exist as "modules" that can be reused in different pathways and perform similar functions on different molecules.
人们提出了许多模型来描述新代谢途径的演变机制。其中包括将新的酶顺序添加到一个短的祖传途径，整个途径的复制和分化，吸纳原有的酶或者把这些机制组装成新的反应途径。这些机制的相对重要性尚不清楚，但基因组研究表明，一条途径中的酶很可能有共同的祖先，这意味着许多途径是逐步进化而来的，途径中预先存在的步骤创造出了新的功能。另一种模型来自于追踪代谢网络中蛋白质结构演化的研究，它指出酶被普遍利用，生物体借用酶在不同的代谢途径中执行相似的功能(在 MANET 数据库中显而易见)。这些征用过程导致了进化酶的嵌合。第三种可能性是，新陈代谢的某些部分可能作为“模块”存在，可以在不同的途径中重复使用，并对不同的分子执行类似的功能。
As well as the evolution of new metabolic pathways, evolution can also cause the loss of metabolic functions. For example, in some [[parasite]]s metabolic processes that are not essential for survival are lost and preformed amino acids, nucleotides and carbohydrates may instead be scavenged from the [[host (biology)|host]].<ref>{{cite journal | vauthors = Lawrence JG | title = Common themes in the genome strategies of pathogens | journal = Current Opinion in Genetics & Development | volume = 15 | issue = 6 | pages = 584–8 | date = December 2005 | pmid = 16188434 | doi = 10.1016/j.gde.2005.09.007 }} {{cite journal | vauthors = Wernegreen JJ | title = For better or worse: genomic consequences of intracellular mutualism and parasitism | journal = Current Opinion in Genetics & Development | volume = 15 | issue = 6 | pages = 572–83 | date = December 2005 | pmid = 16230003 | doi = 10.1016/j.gde.2005.09.013 }}</ref> Similar reduced metabolic capabilities are seen in [[endosymbiont|endosymbiotic]] organisms.<ref>{{cite journal | vauthors = Pál C, Papp B, Lercher MJ, Csermely P, Oliver SG, Hurst LD | title = Chance and necessity in the evolution of minimal metabolic networks | journal = Nature | volume = 440 | issue = 7084 | pages = 667–70 | date = March 2006 | pmid = 16572170 | doi = 10.1038/nature04568 | s2cid = 4424895 | bibcode = 2006Natur.440..667P }}</ref>
As well as the evolution of new metabolic pathways, evolution can also cause the loss of metabolic functions. For example, in some [[parasite]]s metabolic processes that are not essential for survival are lost and preformed amino acids, nucleotides and carbohydrates may instead be scavenged from the [[host (biology)|host]].<ref>{{cite journal | vauthors = Lawrence JG | title = Common themes in the genome strategies of pathogens | journal = Current Opinion in Genetics & Development | volume = 15 | issue = 6 | pages = 584–8 | date = December 2005 | pmid = 16188434 | doi = 10.1016/j.gde.2005.09.007 }} {{cite journal | vauthors = Wernegreen JJ | title = For better or worse: genomic consequences of intracellular mutualism and parasitism | journal = Current Opinion in Genetics & Development | volume = 15 | issue = 6 | pages = 572–83 | date = December 2005 | pmid = 16230003 | doi = 10.1016/j.gde.2005.09.013 }}</ref> Similar reduced metabolic capabilities are seen in [[endosymbiont|endosymbiotic]] organisms.<ref>{{cite journal | vauthors = Pál C, Papp B, Lercher MJ, Csermely P, Oliver SG, Hurst LD | title = Chance and necessity in the evolution of minimal metabolic networks | journal = Nature | volume = 440 | issue = 7084 | pages = 667–70 | date = March 2006 | pmid = 16572170 | doi = 10.1038/nature04568 | s2cid = 4424895 | bibcode = 2006Natur.440..667P }}</ref>
As well as the evolution of new metabolic pathways, evolution can also cause the loss of metabolic functions. For example, in some parasites metabolic processes that are not essential for survival are lost and preformed amino acids, nucleotides and carbohydrates may instead be scavenged from the host. Similar reduced metabolic capabilities are seen in endosymbiotic organisms.
As well as the evolution of new metabolic pathways, evolution can also cause the loss of metabolic functions. For example, in some parasites metabolic processes that are not essential for survival are lost and preformed amino acids, nucleotides and carbohydrates may instead be scavenged from the host. Similar reduced metabolic capabilities are seen in endosymbiotic organisms.
除了新的代谢途径的进化，演化也会导致代谢功能的丧失。例如，在某些寄生物中，一些并非生存必需的代谢过程丢失了，而预先形成的氨基酸、核苷酸和碳水化合物可能会从寄主那里被清除。在内共生生物体中也可以看到类似的代谢能力下降。
==Investigation and manipulation==
==Investigation and manipulation==
[[Metabolic network of the Arabidopsis thaliana citric acid cycle. Enzymes and metabolites are shown as red squares and the interactions between them as black lines.]]
[[Metabolic network of the Arabidopsis thaliana citric acid cycle. Enzymes and metabolites are shown as red squares and the interactions between them as black lines.]]
[代谢网络的拟南芥三羧酸循环。酶和代谢物显示为红色方块，它们之间的相互作用显示为黑线。]
[拟南芥三羧酸循环的代谢网络。酶和代谢物显示为红色方块，它们之间的相互作用显示为黑线。]
Classically, metabolism is studied by a [[reductionism|reductionist]] approach that focuses on a single metabolic pathway. Particularly valuable is the use of [[radioactive tracer]]s at the whole-organism, tissue and cellular levels, which define the paths from precursors to final products by identifying radioactively labelled intermediates and products.<ref>{{cite journal | vauthors = Rennie MJ | title = An introduction to the use of tracers in nutrition and metabolism | journal = The Proceedings of the Nutrition Society | volume = 58 | issue = 4 | pages = 935–44 | date = November 1999 | pmid = 10817161 | doi = 10.1017/S002966519900124X | doi-access = free }}</ref> The enzymes that catalyze these chemical reactions can then be [[protein purification|purified]] and their [[enzyme kinetics|kinetics]] and responses to [[enzyme inhibitor|inhibitors]] investigated. A parallel approach is to identify the small molecules in a cell or tissue; the complete set of these molecules is called the [[metabolome]]. Overall, these studies give a good view of the structure and function of simple metabolic pathways, but are inadequate when applied to more complex systems such as the metabolism of a complete cell.<ref>{{cite journal | vauthors = Phair RD | title = Development of kinetic models in the nonlinear world of molecular cell biology | journal = Metabolism | volume = 46 | issue = 12 | pages = 1489–95 | date = December 1997 | pmid = 9439549 | doi = 10.1016/S0026-0495(97)90154-2 }}</ref>
Classically, metabolism is studied by a [[reductionism|reductionist]] approach that focuses on a single metabolic pathway. Particularly valuable is the use of [[radioactive tracer]]s at the whole-organism, tissue and cellular levels, which define the paths from precursors to final products by identifying radioactively labelled intermediates and products.<ref>{{cite journal | vauthors = Rennie MJ | title = An introduction to the use of tracers in nutrition and metabolism | journal = The Proceedings of the Nutrition Society | volume = 58 | issue = 4 | pages = 935–44 | date = November 1999 | pmid = 10817161 | doi = 10.1017/S002966519900124X | doi-access = free }}</ref> The enzymes that catalyze these chemical reactions can then be [[protein purification|purified]] and their [[enzyme kinetics|kinetics]] and responses to [[enzyme inhibitor|inhibitors]] investigated. A parallel approach is to identify the small molecules in a cell or tissue; the complete set of these molecules is called the [[metabolome]]. Overall, these studies give a good view of the structure and function of simple metabolic pathways, but are inadequate when applied to more complex systems such as the metabolism of a complete cell.<ref>{{cite journal | vauthors = Phair RD | title = Development of kinetic models in the nonlinear world of molecular cell biology | journal = Metabolism | volume = 46 | issue = 12 | pages = 1489–95 | date = December 1997 | pmid = 9439549 | doi = 10.1016/S0026-0495(97)90154-2 }}</ref>
Classically, metabolism is studied by a reductionist approach that focuses on a single metabolic pathway. Particularly valuable is the use of radioactive tracers at the whole-organism, tissue and cellular levels, which define the paths from precursors to final products by identifying radioactively labelled intermediates and products. The enzymes that catalyze these chemical reactions can then be purified and their kinetics and responses to inhibitors investigated. A parallel approach is to identify the small molecules in a cell or tissue; the complete set of these molecules is called the metabolome. Overall, these studies give a good view of the structure and function of simple metabolic pathways, but are inadequate when applied to more complex systems such as the metabolism of a complete cell.
Classically, metabolism is studied by a reductionist approach that focuses on a single metabolic pathway. Particularly valuable is the use of radioactive tracers at the whole-organism, tissue and cellular levels, which define the paths from precursors to final products by identifying radioactively labelled intermediates and products. The enzymes that catalyze these chemical reactions can then be purified and their kinetics and responses to inhibitors investigated. A parallel approach is to identify the small molecules in a cell or tissue; the complete set of these molecules is called the metabolome. Overall, these studies give a good view of the structure and function of simple metabolic pathways, but are inadequate when applied to more complex systems such as the metabolism of a complete cell.
传统上，新陈代谢的研究采用还原法，侧重于单一的新陈代谢途径。特别有价值的是在整个有机体、组织和细胞水平上使用放射性示踪剂，通过追踪携带放射性标记的中间物和产品来获知从前体到最终产品的路径。然后可以纯化催化这些化学反应的酶，并研究其动力学和对抑制剂的反应。一个并行的方法是识别细胞或组织中的小分子；这些分子的完整集合被称为代谢组。总的来说，这些研究可以很好地了解简单代谢途径的结构和功能，但当应用于更复杂的系统（如一个完整细胞的代谢时），这些研究是不够的。
An idea of the complexity of the metabolic networks in cells that contain thousands of different enzymes is given by the figure showing the interactions between just 43 proteins and 40 metabolites to the right: the sequences of genomes provide lists containing anything up to 26.500 genes. However, it is now possible to use this genomic data to reconstruct complete networks of biochemical reactions and produce more holistic mathematical models that may explain and predict their behavior. These models are especially powerful when used to integrate the pathway and metabolite data obtained through classical methods with data on gene expression from proteomic and DNA microarray studies. Using these techniques, a model of human metabolism has now been produced, which will guide future drug discovery and biochemical research. These models are now used in network analysis, to classify human diseases into groups that share common proteins or metabolites.
An idea of the complexity of the metabolic networks in cells that contain thousands of different enzymes is given by the figure showing the interactions between just 43 proteins and 40 metabolites to the right: the sequences of genomes provide lists containing anything up to 26.500 genes. However, it is now possible to use this genomic data to reconstruct complete networks of biochemical reactions and produce more holistic mathematical models that may explain and predict their behavior. These models are especially powerful when used to integrate the pathway and metabolite data obtained through classical methods with data on gene expression from proteomic and DNA microarray studies. Using these techniques, a model of human metabolism has now been produced, which will guide future drug discovery and biochemical research. These models are now used in network analysis, to classify human diseases into groups that share common proteins or metabolites.
细胞中包含数千种不同酶的代谢网络，这种复杂性概念可以在右图中看到，右图显示了43种蛋白质和40种代谢物之间的相互作用: 基因组序列提供了包含26.500个基因的列表。然而，现在能够利用这些基因组数据来重建完整的生化反应网络，并产生更全面的数学模型来解释和预测它们的行为。这些模型在用于整合通过经典方法获得的途径和代谢物数据以及蛋白质组学和DNA微阵列研究的基因表达数据时特别强大。利用这些技术，现在已经产生了一个人类代谢的模型，这将指导未来的药物发现和生化研究。这些模型现在被用于网络分析，将人类疾病划分为具有共同蛋白质或代谢物的群体。
Bacterial metabolic networks are a striking example of [[Bow tie (biology)|bow-tie]]<ref name="pmid15331224">{{cite journal | vauthors = Csete M, Doyle J | title = Bow ties, metabolism and disease | journal = Trends in Biotechnology | volume = 22 | issue = 9 | pages = 446–50 | date = September 2004 | pmid = 15331224 | pmc = | doi = 10.1016/j.tibtech.2004.07.007 }}</ref><ref name="PMID12874056">{{cite journal | vauthors = Ma HW, Zeng AP | title = The connectivity structure, giant strong component and centrality of metabolic networks | journal = Bioinformatics | volume = 19 | issue = 11 | pages = 1423–30 | date = July 2003 | pmid = 12874056 | doi = 10.1093/bioinformatics/btg177 | citeseerx = 10.1.1.605.8964 }}</ref><ref name="PMID16916470">{{cite journal | vauthors = Zhao J, Yu H, Luo JH, Cao ZW, Li YX | title = Hierarchical modularity of nested bow-ties in metabolic networks | journal = BMC Bioinformatics | volume = 7 | pages = 386 | date = August 2006 | pmid = 16916470 | pmc = 1560398 | doi = 10.1186/1471-2105-7-386 | arxiv = q-bio/0605003 | bibcode = 2006q.bio.....5003Z }}</ref> organization, an architecture able to input a wide range of nutrients and produce a large variety of products and complex macromolecules using a relatively few intermediate common currencies.
Bacterial metabolic networks are a striking example of [[Bow tie (biology)|bow-tie]]<ref name="pmid15331224">{{cite journal | vauthors = Csete M, Doyle J | title = Bow ties, metabolism and disease | journal = Trends in Biotechnology | volume = 22 | issue = 9 | pages = 446–50 | date = September 2004 | pmid = 15331224 | pmc = | doi = 10.1016/j.tibtech.2004.07.007 }}</ref><ref name="PMID12874056">{{cite journal | vauthors = Ma HW, Zeng AP | title = The connectivity structure, giant strong component and centrality of metabolic networks | journal = Bioinformatics | volume = 19 | issue = 11 | pages = 1423–30 | date = July 2003 | pmid = 12874056 | doi = 10.1093/bioinformatics/btg177 | citeseerx = 10.1.1.605.8964 }}</ref><ref name="PMID16916470">{{cite journal | vauthors = Zhao J, Yu H, Luo JH, Cao ZW, Li YX | title = Hierarchical modularity of nested bow-ties in metabolic networks | journal = BMC Bioinformatics | volume = 7 | pages = 386 | date = August 2006 | pmid = 16916470 | pmc = 1560398 | doi = 10.1186/1471-2105-7-386 | arxiv = q-bio/0605003 | bibcode = 2006q.bio.....5003Z }}</ref> organization, an architecture able to input a wide range of nutrients and produce a large variety of products and complex macromolecules using a relatively few intermediate common currencies.
Bacterial metabolic networks are a striking example of bow-tie organization, an architecture able to input a wide range of nutrients and produce a large variety of products and complex macromolecules using a relatively few intermediate common currencies.
Bacterial metabolic networks are a striking example of bow-tie organization, an architecture able to input a wide range of nutrients and produce a large variety of products and complex macromolecules using a relatively few intermediate common currencies.
细菌代谢网络是蝴蝶结结构的一个突出例子，这种架构能够输入多种营养物质，并利用相对较少的中间通货生产出大量产品和复杂的大分子。
A major technological application of this information is [[metabolic engineering]]. Here, organisms such as [[yeast]], plants or [[bacteria]] are genetically modified to make them more useful in [[biotechnology]] and aid the production of [[drug]]s such as [[antibiotic]]s or industrial chemicals such as [[1,3-Propanediol|1,3-propanediol]] and [[shikimic acid]].<ref>{{cite journal | vauthors = Thykaer J, Nielsen J | title = Metabolic engineering of beta-lactam production | journal = Metabolic Engineering | volume = 5 | issue = 1 | pages = 56–69 | date = January 2003 | pmid = 12749845 | doi = 10.1016/S1096-7176(03)00003-X }}
A major technological application of this information is [[metabolic engineering]]. Here, organisms such as [[yeast]], plants or [[bacteria]] are genetically modified to make them more useful in [[biotechnology]] and aid the production of [[drug]]s such as [[antibiotic]]s or industrial chemicals such as [[1,3-Propanediol|1,3-propanediol]] and [[shikimic acid]].<ref>{{cite journal | vauthors = Thykaer J, Nielsen J | title = Metabolic engineering of beta-lactam production | journal = Metabolic Engineering | volume = 5 | issue = 1 | pages = 56–69 | date = January 2003 | pmid = 12749845 | doi = 10.1016/S1096-7176(03)00003-X }}
A major technological application of this information is metabolic engineering. Here, organisms such as yeast, plants or bacteria are genetically modified to make them more useful in biotechnology and aid the production of drugs such as antibiotics or industrial chemicals such as 1,3-propanediol and shikimic acid. These genetic modifications usually aim to reduce the amount of energy used to produce the product, increase yields and reduce the production of wastes.
A major technological application of this information is metabolic engineering. Here, organisms such as yeast, plants or bacteria are genetically modified to make them more useful in biotechnology and aid the production of drugs such as antibiotics or industrial chemicals such as 1,3-propanediol and shikimic acid. These genetic modifications usually aim to reduce the amount of energy used to produce the product, increase yields and reduce the production of wastes.
这些信息的一个主要技术应用是代谢工程学。在应用中，酵母、植物或细菌等生物体都可经过基因改造，使它们在生物技术方面更有用处，同时有助于生产抗生素等药物或工业化学品（如1,3- 丙二醇和莽草酸）。这些基因改造通常旨在减少生产产品所使用的能源，提高产量和减少废物的产生。
==History==
==History==
The term metabolism is derived from French "métabolisme" or Ancient Greek μεταβολή – "Metabole" for "a change" which derived from μεταβάλλ –"Metaballein" means "To change"
The term metabolism is derived from French "métabolisme" or Ancient Greek μεταβολή – "Metabole" for "a change" which derived from μεταβάλλ –"Metaballein" means "To change"
新陈代谢这一术语源于法语“ métabolisme”或古希腊语 μταβoλλ something-“ Metaballein” 意为“改变”
新陈代谢这一术语源于法语“ métabolisme”或古希腊语 μταβoλλ -“Metabole”意为某种改变，它源自意为“去改变”的“ Metaballein”
[[File:Aristotle's metabolism.png|thumb|right|upright=1.4|[[Aristotle's biology|Aristotle's metabolism]] as an open flow model]]
[[File:Aristotle's metabolism.png|thumb|right|upright=1.4|[[Aristotle's biology|Aristotle's metabolism]] as an open flow model]]
Ibn al-Nafis described metabolism in his 1260 AD work titled Al-Risalah al-Kamiliyyah fil Siera al-Nabawiyyah (The Treatise of Kamil on the Prophet's Biography) which included the following phrase "Both the body and its parts are in a continuous state of dissolution and nourishment, so they are inevitably undergoing permanent change."
Ibn al-Nafis described metabolism in his 1260 AD work titled Al-Risalah al-Kamiliyyah fil Siera al-Nabawiyyah (The Treatise of Kamil on the Prophet's Biography) which included the following phrase "Both the body and its parts are in a continuous state of dissolution and nourishment, so they are inevitably undergoing permanent change."
伊本·纳菲斯 Ibn al-Nafis 在其公元1260年的著作《 Al-Risalah al-Kamiliyyah fil Siera al-Nabawiyyah 》(《卡米尔关于先知传记的论述》)中描述了新陈代谢，其中包括以下短语: ”身体及其部分处于持续的溶解和营养状态，因此它们不可避免地要经历永久性的变化
伊本·纳菲斯 Ibn al-Nafis 在其公元1260年的著作《 Al-Risalah al-Kamiliyyah fil Siera al-Nabawiyyah 》(《卡米尔关于先知传记的论述》)中描述了新陈代谢，其中包括以下短语: ”身体及其部分处于持续的溶解和营养状态，因此它们不可避免地要经历永久性的变化。
===Application of the scientific method===
===Application of the scientific method===
The history of the scientific study of metabolism spans several centuries and has moved from examining whole animals in early studies, to examining individual metabolic reactions in modern biochemistry. The first controlled experiments in human metabolism were published by Santorio Santorio in 1614 in his book Ars de statica medicina. He described how he weighed himself before and after eating, sleep, working, sex, fasting, drinking, and excreting. He found that most of the food he took in was lost through what he called "insensible perspiration".
The history of the scientific study of metabolism spans several centuries and has moved from examining whole animals in early studies, to examining individual metabolic reactions in modern biochemistry. The first controlled experiments in human metabolism were published by Santorio Santorio in 1614 in his book Ars de statica medicina. He described how he weighed himself before and after eating, sleep, working, sex, fasting, drinking, and excreting. He found that most of the food he took in was lost through what he called "insensible perspiration".
新陈代谢的科学研究历史跨越了几个世纪，从早期研究中对动物整体的研究，到现代生物化学中对单个代谢反应的研究。 人类新陈代谢的第一个对照实验是由圣托里奥·桑托里奥 Santorio Santorio于1614年在他的著作《静态医学》中发表的。他描述了自己在进食、睡觉、工作、性交、禁食、饮水和排泄前后的体重。他发现他摄入的大部分食物都是通过他所谓的“无知觉的汗液”流失的。
[[File:SantoriosMeal.jpg|thumb|right|upright=0.7|[[Santorio Santorio]] in his steelyard balance, from ''Ars de statica medicina'', first published 1614]]
[[File:SantoriosMeal.jpg|thumb|right|upright=0.7|[[Santorio Santorio]] in his steelyard balance, from ''Ars de statica medicina'', first published 1614]]
[[Santorio Santorio in his steelyard balance, from Ars de statica medicina, first published 1614]]
[[Santorio Santorio in his steelyard balance, from Ars de statica medicina, first published 1614]]
[ Santorio Santorio 在他的杆秤上，出自静态医学，1614年首次发表
[ Santorio Santorio 在他的杆秤上，来自静态医学，1614年首次发表
In these early studies, the mechanisms of these metabolic processes had not been identified and a [[vitalism|vital force]] was thought to animate living tissue.<ref>{{cite book|url=https://archive.org/details/historyofscience04willuoft/page/n7/mode/2up|title=Modern Development of the Chemical and Biological Sciences|vauthors=Williams HA|date=1904|publisher=Harper and Brothers|isbn=|series=A History of Science: in Five Volumes|volume=IV|location=New York|pages=184–185|access-date=26 March 2007}}</ref> In the 19th century, when studying the [[fermentation (food)|fermentation]] of sugar to [[ethanol|alcohol]] by [[yeast]], [[Louis Pasteur]] concluded that fermentation was catalyzed by substances within the yeast cells he called "ferments". He wrote that "alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells."<ref>{{cite journal | vauthors = Manchester KL | title = Louis Pasteur (1822-1895)--chance and the prepared mind | journal = Trends in Biotechnology | volume = 13 | issue = 12 | pages = 511–5 | date = December 1995 | pmid = 8595136 | doi = 10.1016/S0167-7799(00)89014-9 }}</ref> This discovery, along with the publication by [[Friedrich Woehler|Friedrich Wöhler]] in 1828 of a paper on the chemical synthesis of [[urea]],<ref>{{cite journal | vauthors = Kinne-Saffran E, Kinne RK | title = Vitalism and synthesis of urea. From Friedrich Wöhler to Hans A. Krebs | journal = American Journal of Nephrology | volume = 19 | issue = 2 | pages = 290–4 | year = 1999 | pmid = 10213830 | doi = 10.1159/000013463 | s2cid = 71727190 }}</ref> and is notable for being the first organic compound prepared from wholly inorganic precursors. This proved that the organic compounds and chemical reactions found in cells were no different in principle than any other part of chemistry.
In these early studies, the mechanisms of these metabolic processes had not been identified and a [[vitalism|vital force]] was thought to animate living tissue.<ref>{{cite book|url=https://archive.org/details/historyofscience04willuoft/page/n7/mode/2up|title=Modern Development of the Chemical and Biological Sciences|vauthors=Williams HA|date=1904|publisher=Harper and Brothers|isbn=|series=A History of Science: in Five Volumes|volume=IV|location=New York|pages=184–185|access-date=26 March 2007}}</ref> In the 19th century, when studying the [[fermentation (food)|fermentation]] of sugar to [[ethanol|alcohol]] by [[yeast]], [[Louis Pasteur]] concluded that fermentation was catalyzed by substances within the yeast cells he called "ferments". He wrote that "alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells."<ref>{{cite journal | vauthors = Manchester KL | title = Louis Pasteur (1822-1895)--chance and the prepared mind | journal = Trends in Biotechnology | volume = 13 | issue = 12 | pages = 511–5 | date = December 1995 | pmid = 8595136 | doi = 10.1016/S0167-7799(00)89014-9 }}</ref> This discovery, along with the publication by [[Friedrich Woehler|Friedrich Wöhler]] in 1828 of a paper on the chemical synthesis of [[urea]],<ref>{{cite journal | vauthors = Kinne-Saffran E, Kinne RK | title = Vitalism and synthesis of urea. From Friedrich Wöhler to Hans A. Krebs | journal = American Journal of Nephrology | volume = 19 | issue = 2 | pages = 290–4 | year = 1999 | pmid = 10213830 | doi = 10.1159/000013463 | s2cid = 71727190 }}</ref> and is notable for being the first organic compound prepared from wholly inorganic precursors. This proved that the organic compounds and chemical reactions found in cells were no different in principle than any other part of chemistry.
In these early studies, the mechanisms of these metabolic processes had not been identified and a vital force was thought to animate living tissue. In the 19th century, when studying the fermentation of sugar to alcohol by yeast, Louis Pasteur concluded that fermentation was catalyzed by substances within the yeast cells he called "ferments". He wrote that "alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells." This discovery, along with the publication by Friedrich Wöhler in 1828 of a paper on the chemical synthesis of urea, and is notable for being the first organic compound prepared from wholly inorganic precursors. This proved that the organic compounds and chemical reactions found in cells were no different in principle than any other part of chemistry.
In these early studies, the mechanisms of these metabolic processes had not been identified and a vital force was thought to animate living tissue. In the 19th century, when studying the fermentation of sugar to alcohol by yeast, Louis Pasteur concluded that fermentation was catalyzed by substances within the yeast cells he called "ferments". He wrote that "alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells." This discovery, along with the publication by Friedrich Wöhler in 1828 of a paper on the chemical synthesis of urea, and is notable for being the first organic compound prepared from wholly inorganic precursors. This proved that the organic compounds and chemical reactions found in cells were no different in principle than any other part of chemistry.
在早期的研究中，这些新陈代谢过程的机制还没有确定，人们认为一种生命力量是生命组织的活力。19世纪，路易-巴斯德Louis Pasteur 在研究酵母菌将糖发酵成酒精时，得出结论：发酵是由酵母细胞内的物质催化的，他称之为 "发酵物"。他写道："酒精发酵是与酵母细胞的生命和组织有关的行为，而与细胞的死亡或腐烂无关"。这一发现连同1828年弗里德里希-沃勒Friedrich Wöhler 发表的一篇关于尿素化学合成的论文，因为是第一个完全由无机前体制备的有机化合物而引人注目。这证明了在细胞中发现的有机化合物和化学反应与化学的任何其他部分在原理上没有什么不同。
It was the discovery of [[enzyme]]s at the beginning of the 20th century by [[Eduard Buchner]] that separated the study of the chemical reactions of metabolism from the biological study of cells, and marked the beginnings of [[biochemistry]].<ref>Eduard Buchner's 1907 [http://nobelprize.org/nobel_prizes/chemistry/laureates/1907/buchner-lecture.html Nobel lecture] at http://nobelprize.org Accessed 20 March 2007</ref> The mass of biochemical knowledge grew rapidly throughout the early 20th century. One of the most prolific of these modern biochemists was [[Hans Adolf Krebs|Hans Krebs]] who made huge contributions to the study of metabolism.<ref>{{cite journal | vauthors = Kornberg H | title = Krebs and his trinity of cycles | journal = Nature Reviews. Molecular Cell Biology | volume = 1 | issue = 3 | pages = 225–8 | date = December 2000 | pmid = 11252898 | doi = 10.1038/35043073 | s2cid = 28092593 }}</ref> He discovered the urea cycle and later, working with [[Hans Kornberg]], the citric acid cycle and the glyoxylate cycle.<ref>{{cite journal |vauthors=Krebs HA, Henseleit K |title=Untersuchungen über die Harnstoffbildung im tierkorper |journal=Z. Physiol. Chem. |volume=210 |issue=1–2 |pages=33–66 |year=1932 |doi=10.1515/bchm2.1932.210.1-2.33}}<br/>
It was the discovery of [[enzyme]]s at the beginning of the 20th century by [[Eduard Buchner]] that separated the study of the chemical reactions of metabolism from the biological study of cells, and marked the beginnings of [[biochemistry]].<ref>Eduard Buchner's 1907 [http://nobelprize.org/nobel_prizes/chemistry/laureates/1907/buchner-lecture.html Nobel lecture] at http://nobelprize.org Accessed 20 March 2007</ref> The mass of biochemical knowledge grew rapidly throughout the early 20th century. One of the most prolific of these modern biochemists was [[Hans Adolf Krebs|Hans Krebs]] who made huge contributions to the study of metabolism.<ref>{{cite journal | vauthors = Kornberg H | title = Krebs and his trinity of cycles | journal = Nature Reviews. Molecular Cell Biology | volume = 1 | issue = 3 | pages = 225–8 | date = December 2000 | pmid = 11252898 | doi = 10.1038/35043073 | s2cid = 28092593 }}</ref> He discovered the urea cycle and later, working with [[Hans Kornberg]], the citric acid cycle and the glyoxylate cycle.<ref>{{cite journal |vauthors=Krebs HA, Henseleit K |title=Untersuchungen über die Harnstoffbildung im tierkorper |journal=Z. Physiol. Chem. |volume=210 |issue=1–2 |pages=33–66 |year=1932 |doi=10.1515/bchm2.1932.210.1-2.33}}<br/>
It was the discovery of enzymes at the beginning of the 20th century by Eduard Buchner that separated the study of the chemical reactions of metabolism from the biological study of cells, and marked the beginnings of biochemistry. The mass of biochemical knowledge grew rapidly throughout the early 20th century. One of the most prolific of these modern biochemists was Hans Krebs who made huge contributions to the study of metabolism. He discovered the urea cycle and later, working with Hans Kornberg, the citric acid cycle and the glyoxylate cycle. Modern biochemical research has been greatly aided by the development of new techniques such as chromatography, X-ray diffraction, NMR spectroscopy, radioisotopic labelling, electron microscopy and molecular dynamics simulations. These techniques have allowed the discovery and detailed analysis of the many molecules and metabolic pathways in cells.
It was the discovery of enzymes at the beginning of the 20th century by Eduard Buchner that separated the study of the chemical reactions of metabolism from the biological study of cells, and marked the beginnings of biochemistry. The mass of biochemical knowledge grew rapidly throughout the early 20th century. One of the most prolific of these modern biochemists was Hans Krebs who made huge contributions to the study of metabolism. He discovered the urea cycle and later, working with Hans Kornberg, the citric acid cycle and the glyoxylate cycle. Modern biochemical research has been greatly aided by the development of new techniques such as chromatography, X-ray diffraction, NMR spectroscopy, radioisotopic labelling, electron microscopy and molecular dynamics simulations. These techniques have allowed the discovery and detailed analysis of the many molecules and metabolic pathways in cells.
爱德华·布赫纳（Eduard Buchner）在20世纪初发现了酶，从而将新陈代谢的化学反应研究与细胞的生物学研究分离开来，标志着生物化学的开始。整个20世纪早期，大量的生物化学知识迅速增长。汉斯·克雷布斯（Hans Krebs）是这些现代生物化学家中最多产的一位，他对新陈代谢的研究做出了巨大的贡献。他发现了尿素循环，后来又与 汉斯·科恩伯格（Hans Kornberg）合作，发现了三羧酸循环和乙醛酸循环。色谱、x射线衍射、核磁共振光谱、放射性同位素标记、电子显微镜和分子动力学模拟等新技术的发展极大地帮助了现代生化研究。这些技术已经允许发现和详细分析细胞中的许多分子和代谢途径。
爱德华·布赫纳（Eduard Buchner）在20世纪初发现了酶，从而将新陈代谢的化学反应研究与细胞的生物学研究分离开来，这标志着生物化学的开始。整个20世纪早期，生物化学知识的总量迅速增长。汉斯·克雷布斯（Hans Krebs）是这些现代生物化学家中最多产的一位，他对新陈代谢的研究做出了巨大的贡献。他发现了尿素循环，后来又与 汉斯·科恩伯格（Hans Kornberg）合作，发现了三羧酸循环和乙醛酸循环。色谱、x射线衍射、核磁共振光谱、放射性同位素标记、电子显微镜和分子动力学模拟等新技术的发展极大地助力了现代生化研究。这些技术已经能够发现和详细分析细胞中的许多分子和代谢途径。
== See also ==
== See also ==