Metabolic Pathways

11 Key excerpts on "Metabolic Pathways"

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  eBook - PDF

  Karp's Cell and Molecular Biology

  • Gerald Karp, Janet Iwasa, Wallace Marshall(Authors)
  • 2021(Publication Date)
  • Wiley

    (Publisher)

  Most of these reactions can be grouped into Metabolic Pathways containing a sequence of chemical reactions. Each is catalyzed by a specific enzyme, and the prod- uct of one reaction is the substrate for the next. The enzymes constituting a metabolic pathway are usually confined to a spe- cific region of the cell, such as the mitochondria or the cytosol. Increasing evidence suggests that the enzymes of a metabolic pathway are often physically linked to one another, a feature that allows the product of one enzyme to be delivered directly as a substrate to the active site of the next enzyme in the reac- tion sequence. The compounds formed in each step along the pathway are metabolic intermediates (or metabolites) that lead ulti- mately to formation of an end product. End products are mol- ecules with a particular role in the cell, such as an amino acid that can be incorporated into a polypeptide or a sugar that can be consumed for its energy content. The Metabolic Pathways of a cell are interconnected at various points so that a com- pound generated by one pathway may be shuttled in a number of directions depending on the requirements of the cell at the time. This section concentrates on aspects of metabolism that lead to the transfer and utilization of chemical energy, a topic drawn on throughout the book. An Overview of Metabolism Metabolic Pathways can be divided into two broad types. Catabolic pathways lead to the disassembly of complex mol- ecules to form simpler products. Catabolic pathways serve two functions: They make available the raw materials from which other molecules can be synthesized, and they provide chemi- cal energy required for the many activities of a cell. As will be discussed at length in the following sections, energy released by catabolic pathways is stored temporarily in two forms: as high-energy phosphates (primarily ATP) and as high-energy electrons (primarily in NADPH).

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  Mathematical Concepts and Methods in Modern Biology

  Using Modern Discrete Models

  • Raina Robeva, Terrell Hodge(Authors)
  • 2013(Publication Date)
  • Academic Press

    (Publisher)

  Chapter 8 Metabolic Pathways Analysis: A Linear Algebraic Approach

  Terrell L. Hodge,

  Department of Mathematics and College of Arts and Sciences Dean’s Office, Western Michigan University, Kalamazoo, MI 49008, USA, [email protected]

  8.1 Introduction

  To quote from a well-known biochemistry textbook [1] , “Metabolism is the overall process through which living systems acquire and utilize free energy to carry out their various functions.” Metabolism is enacted through Metabolic Pathways: chains of consecutive enzymatic reactions that produce specific products for use by an organism. As explored by biologists and biochemists, there are hundreds of such “chains of reactions” fitting together in many complex (and sometimes not well-understood) ways. For example, the single bacterium Escherichia coli is known to have 600–700 metabolic reactions. Standard (bio)chemical diagrams of such systems of reactions for multiple cellular reactions can easily take up wall-sized charts across multiple walls. To get a sample of this (with relatively uncomplicated diagrams) in the case of E. coli , go to the Kegg reference pathway site http://www.genome.jp/kegg/pathway/map/map01100.html . Similar diagrams exist for human and animal cell metabolism, with even more complexity; a portion is shown below in Figure 8.1 . The metabolites in a metabolic pathway are usually taken to be the substrates, intermediates, and reactants in a chain of reactions.

  Figure 8.1 A representation of a portion of the Metabolic Pathways for human and animal cell metabolism, from http://www.genome.jp/kegg-bin/show_pathway?org_name=map&mapno=01100&mapscale=1.0&show_description=show .

  So why the interest? Cellular metabolism is the complex set of chemical reactions that enable a cell to extract energy and other necessities for life from nutrients, and to build the new structures it needs to live and to reproduce. While it may not provide a metaphysical answer to the question “Why are we alive?” metabolism certainly provides a physical answer to the question of how our cells, and hence ourselves, are able to exist, to grow, and, ultimately, what fails and results in death. The study of cellular metabolism is at the heart of numerous questions and basic research about health, such as aging, and on the emerging sidelines as a consideration for others, such as autism. The degree of interconnectedness of our bodies and our environment, through metabolic interactions in the cells of our gut and numerous other cells1 that we host there, has emerged as a hot research topic, via the study of the microbiome (resp., metabalome), like a biosphere of the gut (resp., a complete profile at a metabolic level). Such research suggests that a broad spectrum of modern diseases, such as diabetes, may be the result of having metabolic processes that are not functioning properly, perhaps due to a lack or imbalance of what were evolutionarily fine-tuned contributions of these non-human cells in our germ-killing, antibiotic present, antibacterial-soap world. See, e.g., [2]

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  Guide to Biochemistry

  • James C. Blackstock(Author)
  • 2014(Publication Date)
  • Butterworth-Heinemann

    (Publisher)

  Cellular metabolism is organized into a network of Metabolic Pathways. A metabolic pathway may be defined as a sequence of coupled enzyme-catalysed reactions (Figure 10.4a). Many Metabolic Pathways are linear sequences although some important pathways are cyclic. The enzymes of Metabolic Pathways are not generally organized intracellularly into defined rows but are available as random molecules in the aqueous milieu of a cellular compartment, e.g. cytosol, or as loosely or tightly bound membrane proteins. Certain substrates/products within a metabolic pathway, called intermediates, may serve as substrates for more than one enzyme available within the same cellular compartment. This gives rise to branch points in metabolism (Figure 10.4b). To permit pertinent production of compounds, the activity of Metabolic Pathways must be regulated (Section 10.6). FIGURE 10.4 Some principles of cellular metabolism. (a) A metabolic pathway. (b) Branch points. (c) Coupling of anabolism to catabolism Metabolic Pathways can be classified as anabolic (from Greek, ana means up) or catabolic (from Greek, cata means down). Anabolic pathways are concerned with synthetic processes and are overall endergonic. Catabolic pathways are concerned with degradation and are exergonic sequences. Catabolism and anabolism are interconnected (Figure 10.4c) through the major chemical link of ATP. Catabolism also provides energy in the form of reducing power (NADPH) necessary for certain biosyntheses (Section 11.8). In general, catabolism is an oxidative process whilst anabolism is a reductive process. An important principle of cellular metabolism is that catabolic pathways are convergent whilst anabolic pathways are divergent. As many different macromolecules are degraded, the degradation is conducted by the progressive entry of the generated intermediates into other pathways which terminate in a few end products

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  Metabolic Engineering

  Concepts and Applications

  • Sang Yup Lee, Jens Nielsen, Gregory Stephanopoulos(Authors)
  • 2021(Publication Date)
  • Wiley-VCH

    (Publisher)

  7 Thermodynamics of Metabolic Pathways Daniel Robert Weilandt* , Maria Masid* , and Vassily Hatzimanikatis

  Laboratory of Computational Systems Biotechnology, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland

  * These authors contributed equally

  7.1 Bioenergetics in Life and in Metabolic Engineering

  Living organisms require a constant supply of energy to maintain their life cycles. Therefore, organisms have evolved strategies to harvest energy stored in their environment to satisfy this constant demand. Energy from the environment comes in different forms, such as, in the chemical bonds of molecules, like glucose and other sugars, as chemical potentials like hydrogen gradients, or as radiation, as the visible light [1] . The second law of thermodynamics dictates that this energy can only be harvested if a thermodynamic force drives the chemical and physical processes involved [2] . As a consequence, the intracellular processes of cells have to be continuously displaced from equilibrium to maintain their functions. Therefore, organisms evolved biochemistry that converts the different forms of energy to energy stored in chemical bonds of compounds such as ATP, NADH, or FADH [3] . These energy‐rich compounds are then used to drive energy‐demanding reactions such as the synthesis of biopolymers like DNA, RNA, lipids, and proteins.

  The biochemical capabilities of a cell are commonly described by metabolic networks known as genome‐scale metabolic models (Chapter 2 ). These networks encompass the set of biochemical reactions that describe the biochemistry necessary to process chemicals and energy from the environment to synthesize the macromolecules required for cellular growth and maintenance functions. Under constant environmental conditions, cells operate at a steady state, i.e. they constantly process nutrients without accumulating any intermediate compounds, yielding either a constant growth rate or a nongrowing state where the synthesis rates of macromolecules equal their degradation rates. This characteristic behavior allows investigating the flux distribution of the biochemical reactions within the cells, for example, using flux balance analysis (FBA). FBA allows to calculate and analyze the stoichiometrically feasible flux distribution of the cells assuming a cellular objective function [4] . It is important to note that in cells the flux distribution is not only subject to the stoichiometric constraints but also to the thermodynamic driving forces. According to the second law of thermodynamics, these thermodynamic driving forces determine the directionality of the reaction net fluxes (Box 7.1 ) [1]

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  Karp's Cell and Molecular Biology

  Concepts and Experiments

  • Gerald Karp, Janet Iwasa, Wallace Marshall(Authors)
  • 2016(Publication Date)
  • Wiley

    (Publisher)

  End products are molecules with a particular role in the cell, such as an amino acid that can be incorpo- rated into a polypeptide or a sugar that can be consumed for its energy content. The Metabolic Pathways of a cell are interconnected at various points so that a compound generated by one pathway may be shuttled in a number of directions depending on the requirements of the cell at the time. We will concentrate in this section on aspects of metabolism that lead to the transfer and utilization of chemical energy, for this topic is one we will draw on throughout the book. Metabolic Pathways can be divided into two broad types. Catabolic pathways lead to the disassembly of complex molecules to form simpler products. Catabolic pathways serve two functions: They make available the raw materials from which other molecules can be synthesized, and they provide chemical energy required for the many activities of a cell. As will be discussed at length, energy released by catabolic pathways is stored temporarily in two forms: as high‐energy phosphates (primarily ATP) and as high‐energy elec- trons (primarily in NADPH). Anabolic pathways lead to the syn- thesis of more complex compounds from simpler starting materials. Anabolic pathways are energy‐requiring and utilize chemical energy released by the exergonic catabolic pathways. FIGURE 3.22 shows a greatly simplified profile of the ways in which the major anabolic and catabolic pathways are intercon- nected. Macromolecules are first disassembled (hydrolyzed) into the building blocks of which they are made (stage I, Figure 3.22). Once macromolecules have been hydrolyzed into their components— amino acids, sugars, and fatty acids—the cell can reutilize the build- ing blocks directly to (1) form other macromolecules of the same class (stage I), (2) convert them into different compounds to make other products, or (3) degrade them further (stages II and III, Figure 3.22) and extract a measure of their free‐energy content.

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  Anatomy and Physiology of Domestic Animals

  • R. Michael Akers, D. Michael Denbow(Authors)
  • 2013(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  Chapter 2 depends on the hydrolysis of one of the phosphate bonds of adenosine triphosphate (ATP). The question becomes, “where did the energy needed to produce the ATP in the first place come from?” This is the crux of the problem; some molecules are catabolized so that others can be created. Simply put, living systems are in a constant thermodynamic battle. As the second law of ther­modynamics indicates, the natural tendency is to­ward equilibrium with dispersion of energy and increasing disorder, or in thermodynamic terms, increased entropy. Living systems, cells, tissues, organs, systems, and organisms are characterized by just the opposite. The degree of complexity and organization in living systems is antithetical to this law. Unlike most of the nonliving universe, open biological systems are able to exchange matter and energy with their surroundings. This allows living systems, while they are alive, to move away from the dispersion and energy equilibrium that the second law of thermo­dynamics dictates. The first law of thermodynamics is familiar as the maxim that energy can neither be created nor destroyed. More formally, it is expressed in this way: the total energy of a system plus its surroundings remains constant. Thus, the exquisite organization and complexity that characterize living systems are at the expense of free energy from the environment; that is, energy that can be harnessed to do work. Thus, living systems are analogous to an oasis in the desert. The oasis, often short-lived in a geological sense, provides a place for relief for the weary traveler. Living sys­tems represent transient conditions during which time nonequi­librium conditions related to energy–matter circumstances exist.

  A fundamental postulate of theoretical biology is that life processes can be explained in terms of chemistry and physics—in other words, in terms of matter and energy. Building on this idea, it can be reasoned that life processes are represented by the myriad of chemical (enzymatic and nonenzymatic) and physical reactions that occur within cells and tissues—in other words, me­tabolism. The yin and yang of metabolism are anabolism and catabolism. Our discussion begins with catabolism.

  The phrase “intermediary metabolism” is often used in nutrition and biochemistry texts. This refers to the many steps of reaction between the initiation of a biochemical process and its completion. For example, the complete oxidation of the critical nutrient glucose begins with uptake of the glucose into the cell and entry of the molecule into a sequence of reactions called glycolysis. This is an example of a biochemical pathway. The steps in the pathway detail the reactions that are required to convert this 6-carbon hexose sugar into two 3-carbon molecules of pyruvate. This process is also called anaerobic respiration. The various molecules that are temporarily produced in the 10 steps of glycolysis are called intermediates. Other biochemical pathways would generate their own specific family of intermediate molecules. Consequently, intermediary metabolism refers to the creation and existence of the hundreds of molecules that are fabricated as various molecules progress toward their final biochemical destination. Finally, although we typically describe important biochemical pathways singly, it needs to be emphasized that a host of biochemical reactions or pathways are occurring simultaneously. Intermediates from one pathway often also supply materials that can be used in other pathways. For example, one of the intermediate steps in glycolysis produces triose phosphate. This molecule can supply the carbon atoms to make pyruvate or alternatively be shuttled out of the glycolysis pathway to produce glycerol that is needed in the anabolic pathway to make triglycerides. A key idea is that regulation and control of the rates of activity of these various, often competing biochemical pathways is critical. Resources must be used effectively and efficiently.

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  General Biology

  • Ashok Kumar Bishoyi(Author)
  • 2020(Publication Date)
  • Delve Publishing

    (Publisher)

  ENERGY AND METABOLISM 8 CONTENTS 8.1 Introduction ..................................................................................... 222 8.2 Metabolic Pathways ......................................................................... 223 8.3 Energy ............................................................................................. 224 8.4 Enzymes .......................................................................................... 230 References ............................................................................................. 234 General Biology 222 8.1 INTRODUCTION The term bioenergetics is used by scientists to demonstrate the concepts of energy transfer through the living systems in the level of tissues and cells. Cellular processes which include development and breakdown of complex molecules take place through periodic and stepwise chemical reactions (Taegtmeyer et al., 1998). Some of the chemical reactions are known as spontaneous reactions that release energy, while others are called non-spontaneous which require energy to take place (Gollnick, 1985; Stanley et al., 1997). Similar to living things which need continuous consumption of food to refill their energy supplies, living cells need to produce more energy to replenish the energy used in chemical reactions taking place continuously (Bottomley, 1985; Jacobus, 1985; Welch et al., 1989). Collectively, all of the cellular chemical reactions occur inside cells. The reactions which generate or consume are referred to as the metabolism of a cell ( Boothby et al., 1936; Neubauer et al., 1992; Flores et al., 2000). Figure 8.1. Most of the living organisms acquire their energy from the sun. Plants utilize photosynthesis to trap sunlight, herbivores consume plants to get energy, and carnivores eat herbivores. Consequent decomposition of animal and plant materials contributes to the nutrient reservoir. [Source: https://philschatz.com/biology-concepts-book/contents/m45437.html]

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  Principles of Biochemistry

  • Donald Voet, Charlotte W. Pratt, Judith G. Voet(Authors)
  • 2014(Publication Date)
  • Wiley

    (Publisher)

  C H A P T E R 1 4 437 Section 1 Overview of Metabolism 1 Overview of Metabolism K E Y C O N C E P T S • Different organisms use different strategies for capturing free energy from their environment and can be classified by their requirement for oxygen. • Mammalian nutrition involves the intake of macronutrients (proteins, carbohydrates, and lipids) and micronutrients (vitamins and minerals). • A metabolic pathway is a series of enzyme-catalyzed reactions, often located in a specific part of the cell. • The flux of material through a metabolic pathway varies with the activities of the enzymes that catalyze irreversible reactions. • These flux-controlling enzymes are regulated by allosteric mechanisms, covalent modification, substrate cycling, and changes in gene expression. A bewildering array of chemical reactions occur in any living cell. Yet the prin- ciples that govern metabolism are the same in all organisms, a result of their common evolutionary origin and the constraints of the laws of thermodynam- ics. In fact, many of the specific reactions of metabolism are common to all organisms, with variations due primarily to differences in the source of the free energy that supports them. A Nutrition Involves Food Intake and Use Nutrition, the intake and utilization of food, affects health, development, and performance. Food supplies the energy that powers life processes and provides the raw materials to build and repair body tissues. The nutritional require- ments of an organism reflect its source of metabolic energy. For example, some prokaryotes are autotrophs (Greek: autos, self  trophos, feeder), which can synthesize all their cellular constituents from simple molecules such as H 2 O, CO 2 , NH 3 , and H 2 S. There are two possible free energy sources for this process.

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  Voet's Principles of Biochemistry

  • Donald Voet, Judith G. Voet, Charlotte W. Pratt(Authors)
  • 2018(Publication Date)
  • Wiley

    (Publisher)

  HAWOONG JEONG, UNIVERSITY OF NOTRE DAME / Science Source Images 443 1 Overview of Metabolism KEY IDEAS • Different organisms use different strategies for capturing free energy from their environment and can be classified by their requirement for oxygen. • Mammalian nutrition involves the intake of macronutrients (proteins, carbohydrates, and lipids) and micronutrients (vitamins and minerals). • A metabolic pathway is a series of enzyme-catalyzed reactions, often located in a specific part of a cell. • The flux of material through a metabolic pathway varies with the activities of the enzymes that catalyze irreversible reactions. • These flux-controlling enzymes are regulated by allosteric mechanisms, covalent modification, substrate cycling, and changes in gene expression. A bewildering array of chemical reactions occur in any living cell. Yet the prin- ciples that govern metabolism are the same in all organisms, a result of their common evolutionary origin and the constraints of the laws of thermodynamics. In fact, many of the specific reactions of metabolism are common to all organ- isms, with variations due primarily to differences in the sources of the free energy that supports them. A Nutrition Involves Food Intake and Use Nutrition, the intake and utilization of food, affects health, development, and performance. Food supplies the energy that powers life processes and provides the raw materials to build and repair body tissues. The nutritional requirements of an organism reflect its source of metabolic energy. For example, some pro- karyotes are autotrophs (Greek: autos, self + trophos, feeder), which can syn- thesize all their cellular constituents from simple molecules such as H 2 O, CO 2 , NH 3 , and H 2 S. There are two possible free energy sources for this process.

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  Textbook of Biochemistry with Clinical Correlations

  • Thomas M. Devlin(Author)
  • 2015(Publication Date)
  • Wiley-Liss

    (Publisher)

  Metabolism consists of two contrast- ing processes, catabolism and anabolism, which together constitute the chemical changes that convert foodstuffs into usable forms of energy and into complex biological molecules. Catabolism is responsible for degradation of ingested foodstuffs or stored fuels such as carbo- hydrate, lipid, and protein into either usable or storable forms of energy. Catabolic reactions generally result in conversion of large complex molecules to smaller molecules (ultimately CO 2 and H 2 O), and in mammals often require consumption of O 2 . Energy-utilizing reac- tions perform various necessary, and in many instances tissue-specific functions, for example, nerve impulse conduction, muscle contraction, growth, and cell division. Catabolic reac- tions are generally exergonic with the released energy generally trapped in the formation of ATP. The oxidative reactions of catabolism transfer reducing equivalents to the coenzymes NAD  and NADP  to form NADH and NADPH. Anabolic pathways are responsible for biosynthesis of large molecules from smaller precursors and require input of energy either in the form of ATP or reducing equivalents of NADPH (see Figure 10.28, p. 391). ATP Links Energy-Producing and Energy-Utilizing Systems The relationship between energy-producing and energy-utilizing functions of cells is illustrated in Figure 14.1. Energy is derived from oxidation of metabolic fuels utilized by the organism usually as carbohydrate, lipid, and protein. The proportion of each fuel utilized as an energy source depends on the tissue and the dietary and hormonal state of the organism. For exam- ple, mature erythrocytes and adult brain in the fed state use only carbohydrate as a source of energy, whereas the liver of a diabetic or fasted individual metabolizes primarily lipid to meet the energy demands. Energy may be consumed during performance of various energy-linked (work) functions, some of which are indicated in Figure 14.1.

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  A First Course in Systems Biology

  • Eberhard Voit(Author)
  • 2017(Publication Date)
  • Garland Science

    (Publisher)

  Escherichia coli, yeast, and mouse, and also for inferring the composition of ill-characterized pathways, for instance, in lesser-known microbial organisms.

  In addition to KEGG and BioCyc, other tools are available for metabolic pathway analysis. For instance, the commercial software package ERGO [26 ] offers a bioinformatics suite with tools supporting comparative analyses of genomes and Metabolic Pathways. Users of ERGO can combine various sources of information, including sequence similarity, protein and gene context, and regulatory and expression data, for optimal functional predictions and for computational reconstructions of large parts of metabolism. Pathway Studio [27 ] allows automated information mining, the identification and interpretation of relationships among genes, proteins, metabolites, and cellular processes, as well as the construction and analysis of pathways. KInfer (Kinetics Inference) [28 ] is a tool for estimating rate constants of systems of reactions from experimental time-series data on metabolite concentrations. Another interesting database of biological pathways is Reactome [29 , 30 ], which contains not only Metabolic Pathways, but also information regarding DNA replication, transcription, translation, the cell cycle, and signaling cascades.

  The Lipid Maps project [31 ] provides information and databases specifically for lipids and lipidomics, a term that was chosen to indicate that the totality of lipids may be comparable to genomics and proteomics in scope and importance. Indeed, the more we learn about lipids, the more we must marvel at the variety of functions that they serve—from energy storage to membranes and to genuine mechanisms of signal transduction. And not to forget: 60% of the human brain is fat.

  Metabolic concentration and flux profiles are usually, but not always, measured at a steady state. In this condition, material is flowing through the system, but all metabolite pools and flux rates remain constant. At a steady state, all fluxes and metabolite concentrations in the system are constant. Moreover, all fluxes entering any given metabolite pool must in overall quantity be equal to all fluxes leaving this pool. These are strong conditions that permit the inference of some fluxes from knowledge of other fluxes. Indeed, if sufficiently many fluxes in the pathway system could be measured, it would be possible to infer all other fluxes. In reality, the number of measured fluxes is almost always too small for a complete inference, but the method of flux balance analysis (see [32 ] and Chapter 3

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