Rate-limiting Step (biochemistry)
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Rate-limiting Step (biochemistry)
In biochemistry, a rate-limiting step is a reaction step that controls the rate of a series of biochemical reactions. The statement is, however, a misunderstanding of how a sequence of enzyme- catalyzed reaction steps operate. Rather than a single step controlling the rate, it has been discovered that multiple steps control the rate. Moreover, each controlling step controls the rate to varying degrees. Blackman (1905) stated as an axiom: "when a process is conditioned as to its rapidity by a number of separate factors, the rate of the process is limited by the pace of the slowest factor." This implies that it should be possible, by studying the behavior of a complicated system such as a metabolic pathway, to characterize a single factor or reaction (namely the slowest), which plays the role of a master or rate-limiting step. In other words, the study of flux control can be simplified to the study of a single enzyme since, by definition, there can only be one 'rate-limiting' step. ...
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Biochemistry
Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, and metabolism. Over the last decades of the 20th century, biochemistry has become successful at explaining living processes through these three disciplines. Almost all List of life sciences, areas of the life sciences are being uncovered and developed through biochemical methodology and research.#Voet, Voet (2005), p. 3. Biochemistry focuses on understanding the chemical basis that allows biomolecule, biological molecules to give rise to the processes that occur within living Cell (biology), cells and between cells,#Karp, Karp (2009), p. 2. in turn relating greatly to the understanding of tissue (biology), tissues and organ (anatomy), organs as well as organism structure and function.#Miller, Miller (2012). p. 62. Biochemistry is closely ...
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Reaction Step
In chemistry, a reaction step of a chemical reaction is defined as: ''"An elementary reaction, constituting one of the stages of a stepwise reaction in which a reaction intermediate (or, for the first step, the reactants) is converted into the next reaction intermediate (or, for the last step, the products) in the sequence of intermediates between reactants and products"''."Definition of reaction step"
Gold Book The International Union of Pure and Applied Chemistry (IUPAC) publishes many books which contain its complete list of definitions. The definitions are divided initially into seven IUPAC ...
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Reaction Rate
The reaction rate or rate of reaction is the speed at which a chemical reaction takes place, defined as proportional to the increase in the concentration of a product per unit time and to the decrease in the concentration of a reactant per unit time. Reaction rates can vary dramatically. For example, the oxidative rusting of iron under Earth's atmosphere is a slow reaction that can take many years, but the combustion of cellulose in a fire is a reaction that takes place in fractions of a second. For most reactions, the rate decreases as the reaction proceeds. A reaction's rate can be determined by measuring the changes in concentration over time. Chemical kinetics is the part of physical chemistry that concerns how rates of chemical reactions are measured and predicted, and how reaction-rate data can be used to deduce probable reaction mechanisms. The concepts of chemical kinetics are applied in many disciplines, such as chemical engineering, enzymology and environmental e ...
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Enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecules known as product (chemistry), products. Almost all metabolism, metabolic processes in the cell (biology), cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps. The study of enzymes is called ''enzymology'' and the field of pseudoenzyme, pseudoenzyme analysis recognizes that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their amino acid sequences and unusual 'pseudocatalytic' properties. Enzymes are known to catalyze more than 5,000 biochemical reaction types. Other biocatalysts include Ribozyme, catalytic RNA molecules, also called ribozymes. They are sometimes descr ...
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Catalysis
Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quickly, very small amounts of catalyst often suffice; mixing, surface area, and temperature are important factors in reaction rate. Catalysts generally react with one or more reactants to form intermediates that subsequently give the final reaction product, in the process of regenerating the catalyst. The rate increase occurs because the catalyst allows the reaction to occur by an alternative mechanism which may be much faster than the noncatalyzed mechanism. However the noncatalyzed mechanism does remain possible, so that the total rate (catalyzed plus noncatalyzed) can only increase in the presence of the catalyst and never decrease. Catalysis may be classified as either homogeneous, whose components are dispersed in the same phase (usual ...
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Metabolic Pathway
In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell (biology), cell. The reactants, products, and Metabolic intermediate, intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical reactions catalyzed by enzymes. In most cases of a metabolic pathway, the product (chemistry), product of one enzyme acts as the substrate (chemistry), substrate for the next. However, side products are considered waste and removed from the cell. Different metabolic pathways function in the position within a Eukaryotic Cell, eukaryotic cell and the significance of the pathway in the given compartment of the cell. For instance, the electron transport chain and oxidative phosphorylation all take place in the mitochondrial membrane. In contrast, glycolysis, pentose phosphate pathway, and Fatty acid synthesis, fatty acid biosynthesis all occur in the cytosol of a cell. There are two types of metabolic pathw ...
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Flux (metabolism)
In biochemistry, metabolic flux (often referred to as flux) is the rate of turnover of molecules through a metabolic pathway. Flux is regulated by the enzymes involved in a pathway. Within cells, regulation of flux is vital for all metabolic pathways to regulate the pathway's activity under different conditions. Flux is therefore of great interest in metabolic network modelling, where it is analysed via flux balance analysis and metabolic control analysis. In this manner, flux is the movement of matter through metabolic networks that are connected by metabolites and cofactors, and is therefore a way of describing the activity of the metabolic network as a whole using a single characteristic. Metabolic flux It is easiest to describe the flux of metabolites through a pathway by considering the reaction steps individually. The flux of the metabolites through each reaction () is the rate of the forward reaction (), less that of the reverse reaction (): J = V_f - V_r At eq ...
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Henrik Kacser
Henrik Kacser FRSE (22 September 1918 – 13 March 1995) was a Austro-Hungarian-born biochemist and geneticist who worked in Britain in the 20th century. Kacser's achievements have been recognised by his election to the Royal Society of Edinburgh in 1990, by an honorary doctorate of the University of Bordeaux II in 1993. Early life Henrik Kacser was born in Câmpina, Romania, in 1918 to Olga and Soma Kacser, an engineer, both Austro-Hungarian. The family moved to Berlin, where Henrik went to the Tretscher School. Before World War II, for educational reasons he moved to Belfast, Northern Ireland, where he did his undergraduate (BSc 1940, MSc 1942) and postgraduate work (PhD 1949) at the Queen's University of Belfast. There he studied chemistry, specialising in physical chemistry as a postgraduate student. He went to the University of Edinburgh in 1952 as a Nuffield Fellow under a scheme to introduce physical scientists into biology. This was to become the start of his work ...
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Metabolic Control Analysis
In biochemistry, metabolic control analysis (MCA) is a mathematical framework for describing Metabolic pathway, metabolic, Cell signaling#Signaling pathways, signaling, and genetic pathways. MCA quantifies how variables, such as fluxes and Chemical species, species concentrations, depend on Network (mathematics), network parameters. In particular, it is able to describe how network-dependent properties, called control coefficients, depend on Local property, local properties called Elasticity of a function, elasticities or elasticity coefficients. MCA was originally developed to describe the control in metabolic pathways but was subsequently extended to describe signaling and Gene regulatory network, genetic networks. MCA has sometimes also been referred to as ''Metabolic Control Theory,'' but this terminology was rather strongly opposed by Henrik Kacser, one of the founders. More recent work has shown that MCA can be Isomorphism, mapped directly on to classical control theory an ...
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Biochemical Systems Theory
Biochemical systems theory is a mathematical modelling framework for biochemical systems, based on ordinary differential equations (ODE), in which biochemical processes are represented using power-law expansions in the variables of the system. This framework, which became known as Biochemical Systems Theory, has been developed since the 1960s by Michael Savageau, Eberhard Voit and others for the systems analysis of biochemical processes. According to Cornish-Bowden (2007) they "regarded this as a general theory of metabolic control, which includes both metabolic control analysis and flux-oriented theory as special cases". Athel Cornish-BowdenMetabolic control analysis FAQ website 18 April 2007. Representation The dynamics of a species is represented by a differential equation with the structure: \frac=\sum_j \mu_ \cdot \gamma_j \prod_k X_k^\, where ''X''''i'' represents one of the ''n''''d'' variables of the model (metabolite concentrations, protein concentrations or levels ...
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Branched Pathways
Branched pathways, also known as branch points (not to be confused with the mathematical branch point), are a common pattern found in metabolism. This is where an intermediate Chemical species, species is chemically made or transformed by multiple enzymatic processes. Linear biochemical pathway, linear pathways only have one enzymatic reaction producing a species and one enzymatic reaction consuming the species. Branched pathways are present in numerous metabolic reactions, including glycolysis, the synthesis of lysine, glutamine, and penicillin, and in the production of the aromatic amino acids. In general, a single branch may have b producing branches and d consuming branches. If the intermediate at the branch point is given by s_i, then the rate of change of s_i is given by: : \sum_^b v_i-\sum_^d v_j=\frac At steady-state when ds_i/dt = 0 the consumption and production rates must be equal: : \sum_^b v_i=\sum_^d v_j Biochemical pathways can be investigated by computer si ...
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Metabolic Control Analysis
In biochemistry, metabolic control analysis (MCA) is a mathematical framework for describing Metabolic pathway, metabolic, Cell signaling#Signaling pathways, signaling, and genetic pathways. MCA quantifies how variables, such as fluxes and Chemical species, species concentrations, depend on Network (mathematics), network parameters. In particular, it is able to describe how network-dependent properties, called control coefficients, depend on Local property, local properties called Elasticity of a function, elasticities or elasticity coefficients. MCA was originally developed to describe the control in metabolic pathways but was subsequently extended to describe signaling and Gene regulatory network, genetic networks. MCA has sometimes also been referred to as ''Metabolic Control Theory,'' but this terminology was rather strongly opposed by Henrik Kacser, one of the founders. More recent work has shown that MCA can be Isomorphism, mapped directly on to classical control theory an ...
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