Jan Sapp
- Published in print:
- 2003
- Published Online:
- September 2007
- ISBN:
- 9780195156195
- eISBN:
- 9780199790340
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780195156195.003.0014
- Subject:
- Biology, Evolutionary Biology / Genetics
This chapter discusses the development of the understanding of genes, enzymes, and microbial genetics. The first breakthrough in understanding how genes actually functioned in the cell was made by ...
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This chapter discusses the development of the understanding of genes, enzymes, and microbial genetics. The first breakthrough in understanding how genes actually functioned in the cell was made by British physician Archibald Garrod, who, in 1908, discovered that a gene controlled biochemical reactions by directing the formation of a single enzyme. Geneticists claim that Garrod's insight was unappreciated and overlooked for several decades until it was rediscovered in the 1940s by George Beadle and Edward Tatum. They proposed that a gene acts by determining the specificity of a particular enzyme and thereby controls, in a primary way, enzymatic synthesis and other metabolic reactions in the organism. Their proposal, known as the “one-gene: one-enzyme” hypothesis, played a directive role in the development of biochemical genetics throughout the 1940s and 1950s.Less
This chapter discusses the development of the understanding of genes, enzymes, and microbial genetics. The first breakthrough in understanding how genes actually functioned in the cell was made by British physician Archibald Garrod, who, in 1908, discovered that a gene controlled biochemical reactions by directing the formation of a single enzyme. Geneticists claim that Garrod's insight was unappreciated and overlooked for several decades until it was rediscovered in the 1940s by George Beadle and Edward Tatum. They proposed that a gene acts by determining the specificity of a particular enzyme and thereby controls, in a primary way, enzymatic synthesis and other metabolic reactions in the organism. Their proposal, known as the “one-gene: one-enzyme” hypothesis, played a directive role in the development of biochemical genetics throughout the 1940s and 1950s.
Pierluigi Frisco
- Published in print:
- 2009
- Published Online:
- September 2009
- ISBN:
- 9780199542864
- eISBN:
- 9780191715679
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780199542864.003.0009
- Subject:
- Mathematics, Applied Mathematics, Mathematical Biology
Splicing P systems, the model of membrane system presented in this chapter, has been inspired by a complex biological process involving DNA molecules and enzymes. After introducing ...
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Splicing P systems, the model of membrane system presented in this chapter, has been inspired by a complex biological process involving DNA molecules and enzymes. After introducing the biological concepts and processes that inspired this model of membrane systems the chapter presents all the results related to it. Splicing P systems are the only model of P systems in this book operating with strings.Less
Splicing P systems, the model of membrane system presented in this chapter, has been inspired by a complex biological process involving DNA molecules and enzymes. After introducing the biological concepts and processes that inspired this model of membrane systems the chapter presents all the results related to it. Splicing P systems are the only model of P systems in this book operating with strings.
Nicholas P. Money
- Published in print:
- 2004
- Published Online:
- September 2007
- ISBN:
- 9780195172270
- eISBN:
- 9780199790258
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780195172270.003.0002
- Subject:
- Biology, Microbiology
Black molds feed by secreting enzymes that dissolve complex molecules, like cellulose, as their filamentous hyphae insinuate themselves in their food sources. Many of the molds that grow in buildings ...
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Black molds feed by secreting enzymes that dissolve complex molecules, like cellulose, as their filamentous hyphae insinuate themselves in their food sources. Many of the molds that grow in buildings represent single phases in complex microbial life cycles. The diversity of mold species is astonishing, but relatively few species are prevalent in homes. Molds have a variety of effects upon human health. Many provoke allergies, some are implicated in fungal sinusitis, and a small subset can cause life-threatening infections. Evidence of the ubiquity of black molds is found in the fact that their growth on the exterior of office buildings in cities is usually mistaken for the effects of pollution.Less
Black molds feed by secreting enzymes that dissolve complex molecules, like cellulose, as their filamentous hyphae insinuate themselves in their food sources. Many of the molds that grow in buildings represent single phases in complex microbial life cycles. The diversity of mold species is astonishing, but relatively few species are prevalent in homes. Molds have a variety of effects upon human health. Many provoke allergies, some are implicated in fungal sinusitis, and a small subset can cause life-threatening infections. Evidence of the ubiquity of black molds is found in the fact that their growth on the exterior of office buildings in cities is usually mistaken for the effects of pollution.
J. Eduardo P. W. Bicudo, William A. Buttemer, Mark A. Chappell, James T. Pearson, and Claus Bech
- Published in print:
- 2010
- Published Online:
- May 2010
- ISBN:
- 9780199228447
- eISBN:
- 9780191711305
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780199228447.003.0004
- Subject:
- Biology, Ornithology
This chapter reviews the diversity of feeding habits among birds and the consequences for their nutritional ecology. Different digestion strategies are also emphasized. Food selection is often ...
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This chapter reviews the diversity of feeding habits among birds and the consequences for their nutritional ecology. Different digestion strategies are also emphasized. Food selection is often treated as a challenge of acquisition, but it is also a problem of utilization, processing and digestion of food. What animals eat and excrete shapes their role in ecological communities and determines their contribution to the flux of energy and materials in ecosystems. The balance between energy acquisition and expenditure is critical for survival and reproductive success. Because energy intake and expenditure integrate all aspects of an individual's life, changes in energy management are closely tied to all aspects of its life-history, including diet quality, nutritional requirements, allocation of time, and body plan.Less
This chapter reviews the diversity of feeding habits among birds and the consequences for their nutritional ecology. Different digestion strategies are also emphasized. Food selection is often treated as a challenge of acquisition, but it is also a problem of utilization, processing and digestion of food. What animals eat and excrete shapes their role in ecological communities and determines their contribution to the flux of energy and materials in ecosystems. The balance between energy acquisition and expenditure is critical for survival and reproductive success. Because energy intake and expenditure integrate all aspects of an individual's life, changes in energy management are closely tied to all aspects of its life-history, including diet quality, nutritional requirements, allocation of time, and body plan.
Slim O. Sassi and Steven A. Benner
- Published in print:
- 2007
- Published Online:
- September 2008
- ISBN:
- 9780199299188
- eISBN:
- 9780191714979
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780199299188.003.0018
- Subject:
- Biology, Evolutionary Biology / Genetics
Ribonucleases, well-known digestive enzymes that supported the development of much of protein science, emerged through an evolutionary history having a rich history of functional recruitment. This ...
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Ribonucleases, well-known digestive enzymes that supported the development of much of protein science, emerged through an evolutionary history having a rich history of functional recruitment. This chapter reviews paleogenetic studies that explored changing function in this family. Similar approaches promise to be powerful tools to advance medicine in a post-genomic world.Less
Ribonucleases, well-known digestive enzymes that supported the development of much of protein science, emerged through an evolutionary history having a rich history of functional recruitment. This chapter reviews paleogenetic studies that explored changing function in this family. Similar approaches promise to be powerful tools to advance medicine in a post-genomic world.
Elizabeth F. Neufeld
- Published in print:
- 2004
- Published Online:
- September 2009
- ISBN:
- 9780198508786
- eISBN:
- 9780191723803
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780198508786.003.0013
- Subject:
- Neuroscience, Disorders of the Nervous System
This chapter traces the development of the field of enzyme replacement. It explores the major remaining problem — i.e., treatment of lysosomal storage diseases with a major neurologic component, ...
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This chapter traces the development of the field of enzyme replacement. It explores the major remaining problem — i.e., treatment of lysosomal storage diseases with a major neurologic component, because of insulation of the brain from the therapeutic enzyme by the blood-brain barrier.Less
This chapter traces the development of the field of enzyme replacement. It explores the major remaining problem — i.e., treatment of lysosomal storage diseases with a major neurologic component, because of insulation of the brain from the therapeutic enzyme by the blood-brain barrier.
Firoze B. Jungalwala
- Published in print:
- 2005
- Published Online:
- September 2009
- ISBN:
- 9780198525387
- eISBN:
- 9780191723872
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780198525387.003.0003
- Subject:
- Neuroscience, Molecular and Cellular Systems
This chapter describes HNK-1 glycans. While HNK-1 glycans have been known for some time, their functional significance has been elusive. The chapter describes findings regarding their roles, in ...
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This chapter describes HNK-1 glycans. While HNK-1 glycans have been known for some time, their functional significance has been elusive. The chapter describes findings regarding their roles, in particular those based on knockout mice. It also describes HNK-1 glycans in glycolipids.Less
This chapter describes HNK-1 glycans. While HNK-1 glycans have been known for some time, their functional significance has been elusive. The chapter describes findings regarding their roles, in particular those based on knockout mice. It also describes HNK-1 glycans in glycolipids.
Koichi Furukawa
- Published in print:
- 2005
- Published Online:
- September 2009
- ISBN:
- 9780198525387
- eISBN:
- 9780191723872
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780198525387.003.0005
- Subject:
- Neuroscience, Molecular and Cellular Systems
This chapter summarizes recent progress in studies of glycosyltransferases and relevant enzymes involved in the synthesis and modification glycosphingolipids. It describes novel approaches to ...
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This chapter summarizes recent progress in studies of glycosyltransferases and relevant enzymes involved in the synthesis and modification glycosphingolipids. It describes novel approaches to clarification of the molecular mechanisms of their effects, focusing on their roles in the membrane microdomains. Future perspectives in this field are also briefly discussed.Less
This chapter summarizes recent progress in studies of glycosyltransferases and relevant enzymes involved in the synthesis and modification glycosphingolipids. It describes novel approaches to clarification of the molecular mechanisms of their effects, focusing on their roles in the membrane microdomains. Future perspectives in this field are also briefly discussed.
Richard Firn
- Published in print:
- 2009
- Published Online:
- February 2010
- ISBN:
- 9780199566839
- eISBN:
- 9780191721700
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780199566839.003.0009
- Subject:
- Biology, Ecology, Biochemistry / Molecular Biology
In biology, many long-held categorisations were finally abandoned because they were no longer productive or meaningful, or they lacked an adequate evolutionary underpinning. This chapter presents a ...
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In biology, many long-held categorisations were finally abandoned because they were no longer productive or meaningful, or they lacked an adequate evolutionary underpinning. This chapter presents a model for the evolution of metabolism that explains why the terms ‘primary metabolism’ and ‘secondary metabolism’ should now be consigned to history.Less
In biology, many long-held categorisations were finally abandoned because they were no longer productive or meaningful, or they lacked an adequate evolutionary underpinning. This chapter presents a model for the evolution of metabolism that explains why the terms ‘primary metabolism’ and ‘secondary metabolism’ should now be consigned to history.
Bryan G. Winchester
- Published in print:
- 2004
- Published Online:
- September 2009
- ISBN:
- 9780198508786
- eISBN:
- 9780191723803
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780198508786.003.0004
- Subject:
- Neuroscience, Disorders of the Nervous System
This chapter begins with a discussion of the molecular genetics of lysosomal enzyme deficiencies. It then discusses the relation of mutations to the structure and function of lysosomal enzymes, and ...
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This chapter begins with a discussion of the molecular genetics of lysosomal enzyme deficiencies. It then discusses the relation of mutations to the structure and function of lysosomal enzymes, and genotype/phenotype correlation in groups of neuronal storage disorders.Less
This chapter begins with a discussion of the molecular genetics of lysosomal enzyme deficiencies. It then discusses the relation of mutations to the structure and function of lysosomal enzymes, and genotype/phenotype correlation in groups of neuronal storage disorders.
Kurt von Figura, Ljudmila V. Borissenko, Jens Fey, Jianhe Peng, Bernhard Schmidt, and Thomas Dierks
- Published in print:
- 2004
- Published Online:
- September 2009
- ISBN:
- 9780198508786
- eISBN:
- 9780191723803
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780198508786.003.0005
- Subject:
- Neuroscience, Disorders of the Nervous System
Two types of modifications are known so far that are required for catalytic activity of lysosomal enzymes. The first type represents the conversion of the catalytically inactive pro-form of ...
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Two types of modifications are known so far that are required for catalytic activity of lysosomal enzymes. The first type represents the conversion of the catalytically inactive pro-form of cysteinyl- and aspartyl-proteinases into the catalytically active mature form by limited proteolysis. This chapter focuses on the second type of modification, which is represented by the posttranslational generation of a Ca-formylglycine (FGly) residue in the catalytic centre of sulfatases. Deficiency of this modification is the molecular cause of multiple sulfatase deficiency (MSD).Less
Two types of modifications are known so far that are required for catalytic activity of lysosomal enzymes. The first type represents the conversion of the catalytically inactive pro-form of cysteinyl- and aspartyl-proteinases into the catalytically active mature form by limited proteolysis. This chapter focuses on the second type of modification, which is represented by the posttranslational generation of a Ca-formylglycine (FGly) residue in the catalytic centre of sulfatases. Deficiency of this modification is the molecular cause of multiple sulfatase deficiency (MSD).
Alessandra d'Azzo
- Published in print:
- 2004
- Published Online:
- September 2009
- ISBN:
- 9780198508786
- eISBN:
- 9780191723803
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780198508786.003.0007
- Subject:
- Neuroscience, Disorders of the Nervous System
Galactosialidosis (GS) is a neurodegenerative lysosomal storage disorder of glycoprotein metabolism. This disease is unique among storage diseases in that it is caused by a primary defect in a ...
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Galactosialidosis (GS) is a neurodegenerative lysosomal storage disorder of glycoprotein metabolism. This disease is unique among storage diseases in that it is caused by a primary defect in a protease, the protective protein/cathepsin A (PPCA). Mutations at the PPCA locus give rise to a prototypical lysosomal disease with heterogeneous clinical manifestations affecting both systemic organs and the nervous system. It is, however, not known to what extent loss of cathepsin A activity contributes to the clinical manifestations in GS patients. The mouse model of GS mimics closely the human severe phenotype and represents a valuable tool for studying the pathogenesis of the disease and developing and implementing therapy. This chapter reviews what has been learned so far about the enzyme and how this knowledge may help to understand the disease.Less
Galactosialidosis (GS) is a neurodegenerative lysosomal storage disorder of glycoprotein metabolism. This disease is unique among storage diseases in that it is caused by a primary defect in a protease, the protective protein/cathepsin A (PPCA). Mutations at the PPCA locus give rise to a prototypical lysosomal disease with heterogeneous clinical manifestations affecting both systemic organs and the nervous system. It is, however, not known to what extent loss of cathepsin A activity contributes to the clinical manifestations in GS patients. The mouse model of GS mimics closely the human severe phenotype and represents a valuable tool for studying the pathogenesis of the disease and developing and implementing therapy. This chapter reviews what has been learned so far about the enzyme and how this knowledge may help to understand the disease.
Larry R. Squire
- Published in print:
- 2009
- Published Online:
- May 2009
- ISBN:
- 9780195380101
- eISBN:
- 9780199864362
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780195380101.003.0014
- Subject:
- Neuroscience, History of Neuroscience
This chapter presents an autobiography of Hans Thoenen. Thoenen elucidated the mechanism of action of 6-hydroxydopamine that led to the serendipitous detection of trans-synaptic enzyme induction. ...
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This chapter presents an autobiography of Hans Thoenen. Thoenen elucidated the mechanism of action of 6-hydroxydopamine that led to the serendipitous detection of trans-synaptic enzyme induction. Subsequently his laboratory made crucial contributions to the field of neurotrophic factors, including the cloning of brain derived neurotrophic and ciliary neurotrophic factor and the analysis of their physiological functions. His early years, career, and achievements are discussed.Less
This chapter presents an autobiography of Hans Thoenen. Thoenen elucidated the mechanism of action of 6-hydroxydopamine that led to the serendipitous detection of trans-synaptic enzyme induction. Subsequently his laboratory made crucial contributions to the field of neurotrophic factors, including the cloning of brain derived neurotrophic and ciliary neurotrophic factor and the analysis of their physiological functions. His early years, career, and achievements are discussed.
Giovanni Zocchi
- Published in print:
- 2018
- Published Online:
- January 2019
- ISBN:
- 9780691173863
- eISBN:
- 9781400890064
- Item type:
- book
- Publisher:
- Princeton University Press
- DOI:
- 10.23943/princeton/9780691173863.001.0001
- Subject:
- Physics, Soft Matter / Biological Physics
This book presents a dynamic new approach to the physics of enzymes and DNA from the perspective of materials science. Unified around the concept of molecular deformability—how proteins and DNA ...
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This book presents a dynamic new approach to the physics of enzymes and DNA from the perspective of materials science. Unified around the concept of molecular deformability—how proteins and DNA stretch, fold, and change shape—the book describes the complex molecules of life from the innovative perspective of materials properties and dynamics, in contrast to structural or purely chemical approaches. It covers a wealth of topics, including nonlinear deformability of enzymes and DNA; the chemo-dynamic cycle of enzymes; supra-molecular constructions with internal stress; nano-rheology and viscoelasticity; and chemical kinetics, Brownian motion, and barrier crossing. Essential reading for researchers in materials science, engineering, and nanotechnology, the book also describes the landmark experiments that have established the materials properties and energy landscape of large biological molecules. The book gives graduate students a working knowledge of model building in statistical mechanics, making it an essential resource for tomorrow's experimentalists in this cutting-edge field. In addition, mathematical methods are introduced in the bio-molecular context. The result is a generalized approach to mathematical problem solving that enables students to apply their findings more broadly.Less
This book presents a dynamic new approach to the physics of enzymes and DNA from the perspective of materials science. Unified around the concept of molecular deformability—how proteins and DNA stretch, fold, and change shape—the book describes the complex molecules of life from the innovative perspective of materials properties and dynamics, in contrast to structural or purely chemical approaches. It covers a wealth of topics, including nonlinear deformability of enzymes and DNA; the chemo-dynamic cycle of enzymes; supra-molecular constructions with internal stress; nano-rheology and viscoelasticity; and chemical kinetics, Brownian motion, and barrier crossing. Essential reading for researchers in materials science, engineering, and nanotechnology, the book also describes the landmark experiments that have established the materials properties and energy landscape of large biological molecules. The book gives graduate students a working knowledge of model building in statistical mechanics, making it an essential resource for tomorrow's experimentalists in this cutting-edge field. In addition, mathematical methods are introduced in the bio-molecular context. The result is a generalized approach to mathematical problem solving that enables students to apply their findings more broadly.
C.N. Hinshelwood
- Published in print:
- 2005
- Published Online:
- September 2007
- ISBN:
- 9780198570257
- eISBN:
- 9780191717659
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780198570257.003.0022
- Subject:
- Physics, Condensed Matter Physics / Materials
This chapter discusses living matter. Topics covered include the creation of order by living things, the place of chemistry in the study of cell phenomena, bacteria, the law of growth, linked enzyme ...
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This chapter discusses living matter. Topics covered include the creation of order by living things, the place of chemistry in the study of cell phenomena, bacteria, the law of growth, linked enzyme systems, adaptation, patterns of chemical reactions, and growth and form.Less
This chapter discusses living matter. Topics covered include the creation of order by living things, the place of chemistry in the study of cell phenomena, bacteria, the law of growth, linked enzyme systems, adaptation, patterns of chemical reactions, and growth and form.
Noureddine Brakch and Mohamed Rholam
- Published in print:
- 2009
- Published Online:
- January 2010
- ISBN:
- 9780195326697
- eISBN:
- 9780199864874
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780195326697.003.0016
- Subject:
- Neuroscience, Molecular and Cellular Systems
Proteases are extremely important signaling molecules that are involved in numerous vital processes. Protease signaling pathways are strictly regulated, and therefore the dysregulation of their ...
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Proteases are extremely important signaling molecules that are involved in numerous vital processes. Protease signaling pathways are strictly regulated, and therefore the dysregulation of their activity can lead to pathologies such as cardiovascular and inflammatory diseases, cancer, and neurological disorders. An illustration of the functional role of proteases in physiological processes is demonstrated in the metabolism of β-amyloid. Under normal physiological conditions, the steady-state level of β-amyloid peptide in the brain is determined by the rate of production from amyloid precursor protein via β- and γ-secretases and rate of degradation by the activity of several known metallopeptidases. In conditions that affect the activity of these proteases (for example, genetic mutations, environmental factors, or age), overactive secretases or underactive β-amyloid-degrading enzymes could shift the balance of amyloid metabolism toward abnormal β-amyloid deposition in the brain, an early and invariant feature of all forms of Alzheimer's disease (AD). These proteases thus represent potential therapeutic targets against AD, and consequently, regulation of their activity by drugs is now considered as an important strategy in the neuroprotection.Less
Proteases are extremely important signaling molecules that are involved in numerous vital processes. Protease signaling pathways are strictly regulated, and therefore the dysregulation of their activity can lead to pathologies such as cardiovascular and inflammatory diseases, cancer, and neurological disorders. An illustration of the functional role of proteases in physiological processes is demonstrated in the metabolism of β-amyloid. Under normal physiological conditions, the steady-state level of β-amyloid peptide in the brain is determined by the rate of production from amyloid precursor protein via β- and γ-secretases and rate of degradation by the activity of several known metallopeptidases. In conditions that affect the activity of these proteases (for example, genetic mutations, environmental factors, or age), overactive secretases or underactive β-amyloid-degrading enzymes could shift the balance of amyloid metabolism toward abnormal β-amyloid deposition in the brain, an early and invariant feature of all forms of Alzheimer's disease (AD). These proteases thus represent potential therapeutic targets against AD, and consequently, regulation of their activity by drugs is now considered as an important strategy in the neuroprotection.
Gary W. Morrow
- Published in print:
- 2016
- Published Online:
- November 2020
- ISBN:
- 9780199860531
- eISBN:
- 9780197563229
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/oso/9780199860531.003.0005
- Subject:
- Chemistry, Organic Chemistry
It is not essential to have a background in enzymology or biochemistry to gain at least an introductory-level understanding of many biosynthetic processes, so this ...
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It is not essential to have a background in enzymology or biochemistry to gain at least an introductory-level understanding of many biosynthetic processes, so this book does not deal with enzymology or enzyme structure or function in any significant way, even though much of the chemistry we will be examining depends almost entirely on enzyme catalysis. Nevertheless, we will refer to enzyme catalysis and the names of specific enzymes throughout the text as we examine biosynthetic processes and reactions in significant detail. So what exactly are enzymes? Simply put, enzymes are naturally occurring proteins that catalyze various biochemical reactions in living systems. As we will see, many of the reactions they catalyze are familiar organic reactions, but have specific purposes and target structures. Generally speaking, enzymes catalyze organic reactions by lowering transition state energies or raising ground state energies of reactants in much the same way as nonenzymatic catalysts in laboratory chemical reactions, though in the case of enzyme catalysis, rate enhancements of as much as 1023 have been reported, far exceeding rate enhancements currently achievable by conventional chemical means. Understanding the interaction of enzymes and substrates (reactants) to form an enzyme–substrate complex (E–S complex) is fundamental to having some appreciation for how enzymes carry out their work. While overly simplistic, the “lock-and-key” model of enzyme–substrate interaction provides an intuitive context for understanding the remarkable substrate specificity of enzyme-mediated reactions. Thus, so-called enzyme active sites or binding sites (the “lock”) will only accept certain specific substrate structures (the “key”), with shape, conformation, intermolecular forces, and other factors determining the lock-and-key fit. Enzymes not only catalyze specific kinds of reactions, they can act specifically on certain compounds or classes of compounds or functional groups, often showing remarkable selectivity and stereospecificity, especially in the recognition and/or introduction of chirality centers in organic molecules. In terms of nomenclature, enzyme names always end with an ase suffix and are typically named in accordance with the substrate they act upon and/or the kind of reaction process they catalyze.
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It is not essential to have a background in enzymology or biochemistry to gain at least an introductory-level understanding of many biosynthetic processes, so this book does not deal with enzymology or enzyme structure or function in any significant way, even though much of the chemistry we will be examining depends almost entirely on enzyme catalysis. Nevertheless, we will refer to enzyme catalysis and the names of specific enzymes throughout the text as we examine biosynthetic processes and reactions in significant detail. So what exactly are enzymes? Simply put, enzymes are naturally occurring proteins that catalyze various biochemical reactions in living systems. As we will see, many of the reactions they catalyze are familiar organic reactions, but have specific purposes and target structures. Generally speaking, enzymes catalyze organic reactions by lowering transition state energies or raising ground state energies of reactants in much the same way as nonenzymatic catalysts in laboratory chemical reactions, though in the case of enzyme catalysis, rate enhancements of as much as 1023 have been reported, far exceeding rate enhancements currently achievable by conventional chemical means. Understanding the interaction of enzymes and substrates (reactants) to form an enzyme–substrate complex (E–S complex) is fundamental to having some appreciation for how enzymes carry out their work. While overly simplistic, the “lock-and-key” model of enzyme–substrate interaction provides an intuitive context for understanding the remarkable substrate specificity of enzyme-mediated reactions. Thus, so-called enzyme active sites or binding sites (the “lock”) will only accept certain specific substrate structures (the “key”), with shape, conformation, intermolecular forces, and other factors determining the lock-and-key fit. Enzymes not only catalyze specific kinds of reactions, they can act specifically on certain compounds or classes of compounds or functional groups, often showing remarkable selectivity and stereospecificity, especially in the recognition and/or introduction of chirality centers in organic molecules. In terms of nomenclature, enzyme names always end with an ase suffix and are typically named in accordance with the substrate they act upon and/or the kind of reaction process they catalyze.
J.Paul Rocchiccioli and John J. V. Mcmurray
- Published in print:
- 2008
- Published Online:
- November 2011
- ISBN:
- 9780198570288
- eISBN:
- 9780191730030
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/acprof:oso/9780198570288.003.0004
- Subject:
- Palliative Care, Patient Care and End-of-Life Decision Making, Pain Management and Palliative Pharmacology
This chapter addresses the state of knowledge in the evidence-based management of heart failure (HF) with medications. Diuretics were amongst the first therapies to be used in the treatment of HF. ...
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This chapter addresses the state of knowledge in the evidence-based management of heart failure (HF) with medications. Diuretics were amongst the first therapies to be used in the treatment of HF. Angiotensin-converting enzyme (ACE) inhibitors are considered the first-line therapy in the management of HF with reduced left-ventricular systolic function. Angiotensin receptor blockers (ARBs) are the most recent class of drugs to be shown to be of benefit in HF. β-Blockers are considered the greatest advance in the treatment of HF since ACE inhibitors and lead to a further substantial reduction in mortality and morbidity. The mechanisms of action, clinical benefits, adverse effects and interactions, and practical uses of these therapies are reported. In addition, the mechanisms of action, clinical benefits, adverse effects and interactions, and practical uses of aldosterone antagonists, hydralazine and isosorbide dinitrate, and cardiac glycosides are described. It also explores the HF with preserved ejection fraction and other pharmacological therapies. Despite the impressive therapeutic armamentarium, patients with HF continue to experience progressive symptoms and shorter life expectancy.Less
This chapter addresses the state of knowledge in the evidence-based management of heart failure (HF) with medications. Diuretics were amongst the first therapies to be used in the treatment of HF. Angiotensin-converting enzyme (ACE) inhibitors are considered the first-line therapy in the management of HF with reduced left-ventricular systolic function. Angiotensin receptor blockers (ARBs) are the most recent class of drugs to be shown to be of benefit in HF. β-Blockers are considered the greatest advance in the treatment of HF since ACE inhibitors and lead to a further substantial reduction in mortality and morbidity. The mechanisms of action, clinical benefits, adverse effects and interactions, and practical uses of these therapies are reported. In addition, the mechanisms of action, clinical benefits, adverse effects and interactions, and practical uses of aldosterone antagonists, hydralazine and isosorbide dinitrate, and cardiac glycosides are described. It also explores the HF with preserved ejection fraction and other pharmacological therapies. Despite the impressive therapeutic armamentarium, patients with HF continue to experience progressive symptoms and shorter life expectancy.
Gary W. Morrow
- Published in print:
- 2016
- Published Online:
- November 2020
- ISBN:
- 9780199860531
- eISBN:
- 9780197563229
- Item type:
- chapter
- Publisher:
- Oxford University Press
- DOI:
- 10.1093/oso/9780199860531.003.0011
- Subject:
- Chemistry, Organic Chemistry
The German chemist Friedrich Wöhler is generally credited with the first laboratory synthesis of a known organic compound (urea) from inorganic materials. He ...
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The German chemist Friedrich Wöhler is generally credited with the first laboratory synthesis of a known organic compound (urea) from inorganic materials. He accomplished this by the simple heating of an inorganic salt, ammonium cyanate (NH4OCN). “I must tell you,” he wrote to his mentor Jöns Jakob Berzelius in 1828, “that I can prepare urea without requiring a kidney of an animal, either man or dog.” While this report may seem relatively minor given the structural simplicity of urea, its impact was revolutionary. For the first time, the preparation and isolation of an organic compound had been achieved in the absence of the elemental “vital force” of living systems previously believed to be required for the construction of all such compounds. This milestone of 19th century organic chemistry was later followed by many others, including Kolbe’s synthesis of acetic acid in 1847 and Fischer’s synthesis of glucose in 1890. With the support of evolving methods for compound separation, purification, and spectroscopic analysis, rapid advances in the sophistication of organic synthesis followed throughout the 20th century, developing in tandem with an ever-deepening understanding of the underlying organic processes associated with living systems. While it is certainly true that syntheses of many structurally complex unnatural compounds of theoretical interest are also among the most remarkable achievements in synthetic strategy, tactical execution, and perseverance, the realm of natural products remains the dominant source for the most challenging and potentially beneficial targets available for such synthetic efforts. Figure 8.1 shows a small selection of some natural (and unnatural) products which have been produced via synthesis over the years, from Wöhler’s time to the present. Note the increasing levels of structural sophistication and stereochemical complexity that have eventually been mastered by practitioners of organic synthesis. In our own time, the traditional boundaries between organic and biological chemistry are disappearing in ways that are likely to transform the design and synthesis of organic molecules, from the construction of synthetic biologicals designed to act as biomarkers, biosensors, or drug delivery agents, to the development of molecular motors, self-replicating macromolecular systems, and even synthetic life forms.
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The German chemist Friedrich Wöhler is generally credited with the first laboratory synthesis of a known organic compound (urea) from inorganic materials. He accomplished this by the simple heating of an inorganic salt, ammonium cyanate (NH4OCN). “I must tell you,” he wrote to his mentor Jöns Jakob Berzelius in 1828, “that I can prepare urea without requiring a kidney of an animal, either man or dog.” While this report may seem relatively minor given the structural simplicity of urea, its impact was revolutionary. For the first time, the preparation and isolation of an organic compound had been achieved in the absence of the elemental “vital force” of living systems previously believed to be required for the construction of all such compounds. This milestone of 19th century organic chemistry was later followed by many others, including Kolbe’s synthesis of acetic acid in 1847 and Fischer’s synthesis of glucose in 1890. With the support of evolving methods for compound separation, purification, and spectroscopic analysis, rapid advances in the sophistication of organic synthesis followed throughout the 20th century, developing in tandem with an ever-deepening understanding of the underlying organic processes associated with living systems. While it is certainly true that syntheses of many structurally complex unnatural compounds of theoretical interest are also among the most remarkable achievements in synthetic strategy, tactical execution, and perseverance, the realm of natural products remains the dominant source for the most challenging and potentially beneficial targets available for such synthetic efforts. Figure 8.1 shows a small selection of some natural (and unnatural) products which have been produced via synthesis over the years, from Wöhler’s time to the present. Note the increasing levels of structural sophistication and stereochemical complexity that have eventually been mastered by practitioners of organic synthesis. In our own time, the traditional boundaries between organic and biological chemistry are disappearing in ways that are likely to transform the design and synthesis of organic molecules, from the construction of synthetic biologicals designed to act as biomarkers, biosensors, or drug delivery agents, to the development of molecular motors, self-replicating macromolecular systems, and even synthetic life forms.
Giovanni Zocchi
- Published in print:
- 2018
- Published Online:
- January 2019
- ISBN:
- 9780691173863
- eISBN:
- 9781400890064
- Item type:
- chapter
- Publisher:
- Princeton University Press
- DOI:
- 10.23943/princeton/9780691173863.003.0003
- Subject:
- Physics, Soft Matter / Biological Physics
Enzymes are catalysts as well as the molecular machines that generate and maintain the nonequilibrium state of the cell. There are roughly two main mechanisms by which enzymes provide the control ...
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Enzymes are catalysts as well as the molecular machines that generate and maintain the nonequilibrium state of the cell. There are roughly two main mechanisms by which enzymes provide the control function for the network of chemical reactions in the cell. One is the presence or absence of the enzyme, controlled by gene expression. The other is allosteric control: the modulation of the activity of an individual enzyme caused by binding of a specific ligand, often a small metabolite, or else caused by so-called post-translational modifications. This chapter addresses what could be variously called the quasi-equilibrium aspects, or steady state, or kinematics, of enzyme operation, and what one learns from time-independent perturbations of this steady state. Topics discussed include Michaelis–Menten kinetics, the method of the DNA springs, force and elastic energy in the enzyme–DNA chimeras, injection of elastic energy vs. activity modulation, and connection to nonlinear dynamics.Less
Enzymes are catalysts as well as the molecular machines that generate and maintain the nonequilibrium state of the cell. There are roughly two main mechanisms by which enzymes provide the control function for the network of chemical reactions in the cell. One is the presence or absence of the enzyme, controlled by gene expression. The other is allosteric control: the modulation of the activity of an individual enzyme caused by binding of a specific ligand, often a small metabolite, or else caused by so-called post-translational modifications. This chapter addresses what could be variously called the quasi-equilibrium aspects, or steady state, or kinematics, of enzyme operation, and what one learns from time-independent perturbations of this steady state. Topics discussed include Michaelis–Menten kinetics, the method of the DNA springs, force and elastic energy in the enzyme–DNA chimeras, injection of elastic energy vs. activity modulation, and connection to nonlinear dynamics.
