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1.
Biosystems ; 226: 104883, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36931555

RESUMO

Although the papers of Kacser and Burns (1973) and Heinrich and Rapoport (1974a,b) are commonly taken as the birth of metabolic control analysis, many of the ideas in them are foreshadowed in earlier papers, from 1956 onwards, when Kacser first argued for taking a systemic view of genetics and biochemistry.


Assuntos
Modelos Biológicos , Metabolismo , Genética , Bioquímica
2.
Theory Biosci ; 141(2): 105-123, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33956294

RESUMO

Disagreement over whether life is inevitable when the conditions can support life remains unresolved, but calculations show that self-organization can arise naturally from purely random effects. Closure to efficient causation, or the need for all specific catalysts used by an organism to be produced internally, implies that a true model of an organism cannot exist, though this does not exclude the possibility that some characteristics can be simulated. Such simulations indicate that there is a limit to how small a self-organizing system can be: much smaller than a bacterial cell, but around the size of a typical virus particle. All current theories of life incorporate, at least implicitly, the idea of catalysis, but they largely ignore the need for metabolic regulation.


Assuntos
Modelos Biológicos , Catálise
3.
Biochimie ; 182: 120-130, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33285219

RESUMO

Zacharias Dische's discovery of feedback inhibition in metabolism was one of the most important in the history of biochemistry. However, his paper was written and published under very difficult circumstances in wartime and passed almost completely unnoticed. It is almost never cited, and the discovery itself is usually attributed to later work of others. Here I provide a discussion of Dische's work, a translation of his paper into English, and a transcription of the original French version, which is almost unobtainable anywhere.


Assuntos
Bioquímica/história , Metabolismo , Animais , História do Século XIX , História do Século XX , Humanos
4.
Biosystems ; 188: 104063, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31715221

RESUMO

Most attempts to define life have concentrated on individual theories, mentioning others hardly at all, but here we compare all of the major current theories. We begin by asking how we know that an entity is alive, and continue by describing the contributions of La Mettrie, Burke, Leduc, Herrera, Bahadur, D'Arcy Thompson and, especially, Schrödinger, whose book What is Life? is a vital starting point. We then briefly describe and discuss (M, R) systems, the hypercycle, the chemoton, autopoiesis and autocatalytic sets. All of these incorporate the idea of circularity to some extent, but all of them fail to take account of mechanisms of metabolic regulation, which we regard as crucial if an organism is to avoid collapsing into a mass of unregulated reactions. In a final section we study the extent to which each of the current theories can aid in the search for a more complete theory of life, and explain the characteristics of metabolic control analysis that make it essential for an adequate understanding of organisms.


Assuntos
Vida , Modelos Biológicos , Biologia de Sistemas/história , Teoria de Sistemas , Europa (Continente) , História do Século XX , História do Século XXI , América do Norte
5.
Orig Life Evol Biosph ; 49(3): 111-145, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31399826

RESUMO

In this review, we describe some of the central philosophical issues facing origins-of-life research and provide a targeted history of the developments that have led to the multidisciplinary field of origins-of-life studies. We outline these issues and developments to guide researchers and students from all fields. With respect to philosophy, we provide brief summaries of debates with respect to (1) definitions (or theories) of life, what life is and how research should be conducted in the absence of an accepted theory of life, (2) the distinctions between synthetic, historical, and universal projects in origins-of-life studies, issues with strategies for inferring the origins of life, such as (3) the nature of the first living entities (the "bottom up" approach) and (4) how to infer the nature of the last universal common ancestor (the "top down" approach), and (5) the status of origins of life as a science. Each of these debates influences the others. Although there are clusters of researchers that agree on some answers to these issues, each of these debates is still open. With respect to history, we outline several independent paths that have led to some of the approaches now prevalent in origins-of-life studies. These include one path from early views of life through the scientific revolutions brought about by Linnaeus (von Linn.), Wöhler, Miller, and others. In this approach, new theories, tools, and evidence guide new thoughts about the nature of life and its origin. We also describe another family of paths motivated by a" circularity" approach to life, which is guided by such thinkers as Maturana & Varela, Gánti, Rosen, and others. These views echo ideas developed by Kant and Aristotle, though they do so using modern science in ways that produce exciting avenues of investigation. By exploring the history of these ideas, we can see how many of the issues that currently interest us have been guided by the contexts in which the ideas were developed. The disciplinary backgrounds of each of these scholars has influenced the questions they sought to answer, the experiments they envisioned, and the kinds of data they collected. We conclude by encouraging scientists and scholars in the humanities and social sciences to explore ways in which they can interact to provide a deeper understanding of the conceptual assumptions, structure, and history of origins-of-life research. This may be useful to help frame future research agendas and bring awareness to the multifaceted issues facing this challenging scientific question.


Assuntos
Biologia/história , Química/história , Historiografia , Informática/história , Origem da Vida , Paleontologia/história , Filosofia/história , História do Século XVI , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , Biologia Molecular/história
6.
FEBS J ; 285(12): 2193-2204, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29498804

RESUMO

Standards for reporting enzymology data (STRENDA) DB is a validation and storage system for enzyme function data that incorporates the STRENDA Guidelines. It provides authors who are preparing a manuscript with a user-friendly, web-based service that checks automatically enzymology data sets entered in the submission form that they are complete and valid before they are submitted as part of a publication to a journal.


Assuntos
Bases de Dados de Proteínas/normas , Ensaios Enzimáticos/normas , Enzimas/metabolismo , Interface Usuário-Computador , Animais , Bactérias/metabolismo , Ensaios Enzimáticos/métodos , Enzimas/química , Enzimas/classificação , Fungos/metabolismo , Guias como Assunto , Humanos , Disseminação de Informação/métodos , Cinética , Publicações Periódicas como Assunto , Plantas/metabolismo , Estudos de Validação como Assunto
7.
J Biosci ; 42(4): 665-670, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29229884

RESUMO

Enthalpy-entropy compensation supposes that differences in activation enthalpy ΔH++ for different reactions (or, typically in biochemistry, the same reaction catalysed by enzymes obtained from different species) may be compensated for by differences in activation entropy ΔS++. At the isokinetic temperature the compensation is exact, so that all samples have the same activity. These ideas have been controversial for several decades, but examples are still frequently reported as evidence of a real phenomenon, nearly all of the reports ignoring or discounting the possibility of a statistical artefact. Even for measurements in pure chemistry artefacts occur often, and they are almost inescapable in enzyme kinetics and other fields that involve biological macromolecules, on account of limited stability and the fact that kinetic equations are normally valid only over a restricted range of temperature. Here I review the current status and correct an error in a recent book chapter.


Assuntos
Adenosina Trifosfatases/metabolismo , Ensaios Enzimáticos/estatística & dados numéricos , Proteínas de Peixes/metabolismo , Animais , Biocatálise , Interpretação Estatística de Dados , Peixes/metabolismo , Cinética , Temperatura , Termodinâmica
8.
J Theor Biol ; 434: 1, 2017 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-28992902
9.
J Theor Biol ; 434: 68-74, 2017 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-28536033

RESUMO

We see the last universal common ancestor of all living organisms, or LUCA, at the evolutionary separation of the Archaea from the Eubacteria, and before the symbiotic event believed to have led to the Eukarya. LUCA is often implicitly taken to be close to the origin of life, and sometimes this is even stated explicitly. However, LUCA already had the capacity to code for many proteins, and had some of the same bioenergetic capacities as modern organisms. An organism at the origin of life must have been vastly simpler, and this invites the question of how to define a living organism. Even if acceptance of the giant viruses as living organisms forces the definition of LUCA to be revised, it will not alter the essential point that LUCA should be regarded as a recent player in the evolution of life.


Assuntos
Origem da Vida , Archaea/citologia , Bactérias/citologia , Biocatálise , Vírus Gigantes/genética , Vida
10.
J Biol Chem ; 291(52): 26739-26749, 2016 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-27815499

RESUMO

Negative cooperativity in enzyme reactions, in which the first event makes subsequent events less favorable, is sometimes well understood at the molecular level, but its physiological role has often been obscure. Negative cooperativity occurs in human glutathione transferase (GST) GSTP1-1 when it binds and neutralizes a toxic nitric oxide adduct, the dinitrosyl-diglutathionyl iron complex (DNDGIC). However, the generality of this behavior across the divergent GST family and its evolutionary significance were unclear. To investigate, we studied 16 different GSTs, revealing that negative cooperativity is present only in more recently evolved GSTs, indicating evolutionary drift in this direction. In some variants, Hill coefficients were close to 0.5, the highest degree of negative cooperativity commonly observed (although smaller values of nH are theoretically possible). As DNDGIC is also a strong inhibitor of GSTs, we suggest negative cooperativity might have evolved to maintain a residual conjugating activity of GST against toxins even in the presence of high DNDGIC concentrations. Interestingly, two human isoenzymes that play a special protective role, safeguarding DNA from DNDGIC, display a classical half-of-the-sites interaction. Analysis of GST structures identified elements that could play a role in negative cooperativity in GSTs. Beside the well known lock-and-key and clasp motifs, other alternative structural interactions between subunits may be proposed for a few GSTs. Taken together, our findings suggest the evolution of self-preservation of enzyme function as a novel facility emerging from negative cooperativity.


Assuntos
Evolução Molecular , Compostos Ferrosos/farmacologia , Glutationa Transferase/química , Glutationa Transferase/metabolismo , Glutationa/análogos & derivados , Óxido Nítrico/metabolismo , Cristalografia por Raios X , Glutationa/farmacologia , Humanos , Cinética
11.
J Theor Biol ; 381: 6-10, 2015 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-25988381

RESUMO

Of the various theories of life that appeared in the second half of the 20th century the chemoton of Tibor Gánti and the (M,R)-systems of Robert Rosen are among the most important, of which the former is rooted in chemical engineering and the latter is highly abstract. Despite apparent differences, in part due to very different ways of presenting them, these two approaches share some important characteristics: both are "closed to efficient causation", which means that they require nothing from their environment, and in particular not catalysts, apart from "food", or chemical species that allow for the production of energy. On the other hand Rosen insisted that a living organism cannot be regarded as a machine, whereas Gánti explicitly discussed its mechanical nature, and the enclosing boundary is explicitly created by the system itself in the chemoton, but is (at best) simply implicit in (M,R)-systems.


Assuntos
Modelos Biológicos , Origem da Vida , Animais , Bioquímica/métodos , Biologia de Sistemas/métodos
12.
Biochimie ; 107 Pt B: 161-6, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25252213

RESUMO

Victor Henri's great contribution to the understanding of enzyme kinetics and mechanism is not always given the credit that it deserves. In addition, his earlier work in experimental psychology is totally unknown to biochemists, and his later work in spectroscopy and photobiology almost equally so. Applying great rigour to his analysis he succeeded in obtaining a model of enzyme action that explained all of the observations available to him, and he showed why the considerable amount of work done in the preceding decade had not led to understanding. His view was that only physical chemistry could explain the behaviour of enzymes, and that models should be judged in accordance with their capacity not only to explain previously known facts but also to predict new observations against which they could be tested. The kinetic equation usually attributed to Michaelis and Menten was in reality due to him. His thesis of 1903 is now available in English.


Assuntos
Bioquímica/história , Enzimas/química , História do Século XIX , História do Século XX , Humanos , Cinética , Fotobiologia/história , Psicologia/história , Psicologia/métodos , Análise Espectral , beta-Frutofuranosidase/química
13.
J Biosci ; 39(1): 13-27, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24499786

RESUMO

Biochemical information has been crucial for the development of evolutionary biology. On the one hand, the sequence information now appearing is producing a huge increase in the amount of data available for phylogenetic analysis; on the other hand, and perhaps more fundamentally, it allows understanding of the mechanisms that make evolution possible. Less well recognized, but just as important, understanding evolutionary biology is essential for understanding many details of biochemistry that would otherwise be mysterious, such as why the structures of NAD and other coenzymes are far more complicated than their functions would seem to require. Courses of biochemistry should thus pay attention to the essential role of evolution in selecting the molecules of life.


Assuntos
Pesquisa Empírica , Religião e Ciência , Humanos
15.
Biochim Biophys Acta ; 1840(6): 1798-807, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24444799

RESUMO

BACKGROUND: Fructose-1,6-bisphosphatase, a major enzyme of gluconeogenesis, is inhibited by AMP, Fru-2,6-P2 and by high concentrations of its substrate Fru-1,6-P2. The mechanism that produces substrate inhibition continues to be obscure. METHODS: Four types of experiments were used to shed light on this: (1) kinetic measurements over a very wide range of substrate concentrations, subjected to detailed statistical analysis; (2) fluorescence studies of mutants in which phenylalanine residues were replaced by tryptophan; (3) effect of Fru-2,6-P2 and Fru-1,6-P2 on the exchange of subunits between wild-type and Glu-tagged oligomers; and (4) kinetic studies of hybrid forms of the enzyme containing subunits mutated at the active site residue tyrosine-244. RESULTS: The kinetic experiments with the wild-type enzyme indicate that the binding of Fru-1,6-P2 induces the appearance of catalytic sites with lower affinity for substrate and lower catalytic activity. Binding of substrate to the high-affinity sites, but not to the low-affinity sites, enhances the fluorescence emission of the Phe219Trp mutant; the inhibitor, Fru-2,6-P2, competes with the substrate for the high-affinity sites. Binding of substrate to the low-affinity sites acts as a "stapler" that prevents dissociation of the tetramer and hence exchange of subunits, and results in substrate inhibition. CONCLUSIONS: Binding of the first substrate molecule, in one dimer of the enzyme, produces a conformational change at the other dimer, reducing the substrate affinity and catalytic activity of its subunits. GENERAL SIGNIFICANCE: Mimics of the substrate inhibition of fructose-1,6-bisphosphatase may provide a future option for combatting both postprandial and fasting hyperglycemia.


Assuntos
Biocatálise , Frutose-Bifosfatase/química , Rim/enzimologia , Animais , Sequência de Bases , Sítios de Ligação , Frutose-Bifosfatase/antagonistas & inibidores , Frutose-Bifosfatase/metabolismo , Frutosedifosfatos/química , Dados de Sequência Molecular , Subunidades Proteicas , Especificidade por Substrato , Suínos
16.
FEBS J ; 281(2): 435-63, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24180270

RESUMO

Methods and equations for analysing the kinetics of enzyme-catalysed reactions were developed at the beginning of the 20th century in two centres in particular; in Paris, by Victor Henri, and, in Berlin, by Leonor Michaelis and Maud Menten. Henri made a detailed analysis of the work in this area that had preceded him, and arrived at a correct equation for the initial rate of reaction. However, his approach was open to the important objection that he took no account of the hydrogen-ion concentration (a subject largely undeveloped in his time). In addition, although he wrote down an expression for the initial rate of reaction and described the hyperbolic form of its dependence on the substrate concentration, he did not appreciate the great advantages that would come from analysis in terms of initial rates rather than time courses. Michaelis and Menten not only placed Henri's analysis on a firm experimental foundation, but also defined the experimental protocol that remains standard today. Here, we review this development, and discuss other scientific contributions of these individuals. The three parts have different authors, as indicated, and do not necessarily agree on all details, in particular about the relative importance of the contributions of Michaelis and Menten on the one hand and of Henri on the other. Rather than force the review into an unrealistic consensus, we consider it appropriate to leave the disagreements visible.


Assuntos
Bioquímica/história , Algoritmos , Berlim , História do Século XIX , História do Século XX , Japão , Cinética , New York , beta-Frutofuranosidase/química
17.
Methods Mol Biol ; 1090: 261-80, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24222421

RESUMO

This chapter describes a practical procedure to dissect metabolic systems, simplify them, and use or derive enzyme rate equations in order to build a mathematical model of a metabolic system and run simulations. We first deal with a simple example, modeling a single enzyme that follows Michaelis-Menten kinetics and operates in the middle of an unbranched metabolic pathway. Next we describe the rules that can be followed to isolate sub-systems from their environment to simulate their behavior. Finally we use examples to show how to derive suitable rate equations, simpler than those needed for mechanistic studies, though adequate to describe the behavior over the physiological range of conditions.Many of the general characteristics of kinetic models will be obvious to readers familiar with the theory of metabolic control analysis (Cornish-Bowden, Fundamentals of Enzyme Kinetics, Wiley-Blackwell, Weinheim, 327-380, 2012), but here we shall not assume such knowledge, as the chapter is directed toward practical application rather than theory.


Assuntos
Simulação por Computador , Modelos Biológicos , Algoritmos , Regulação Alostérica , Vias Biossintéticas , Ensaios Enzimáticos , Cinética , Fosfotransferases (Aceptor do Grupo Álcool)/química , Proteínas de Plantas/química , Software , Processos Estocásticos , Treonina Desidratase/química
18.
FEBS J ; 281(2): 621-32, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23910900

RESUMO

The paper that introduced biochemists to the idea of allosteric feedback inhibition [Monod J, Changeux J-P & Jacob F (1963) J Mol Biol 6, 306-329] is now 50 years old, and the two papers on models for enzyme cooperativity that followed it [Monod J, Wyman J & Changeux J-P (1965) J Mol Biol 12, 88-118; Koshland DE, Némethy G & Filmer D (1966) Biochemistry 5, 365-385] are almost as old. All of these papers continue to be heavily cited today - more in the 21st century than they were in the last two decades of the 20th. This is because they continue to be central for understanding enzyme regulation, and increasingly important in the age of systems biology.


Assuntos
Enzimas/química , Algoritmos , Regulação Alostérica , Retroalimentação Fisiológica , Cinética , Modelos Químicos , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Especificidade por Substrato
19.
FEBS Lett ; 587(17): 2711, 2013 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-23899672
20.
Nature ; 500(7461): 157-8, 2013 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-23903659
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