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	<title>Comments on: Metabolic networks</title>
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	<link>http://alanrendall.wordpress.com/2009/07/24/metabolic-networks/</link>
	<description>A mathematician thinks aloud</description>
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		<title>By: Chemical reaction network theory &#171; Hydrobates</title>
		<link>http://alanrendall.wordpress.com/2009/07/24/metabolic-networks/#comment-419</link>
		<dc:creator><![CDATA[Chemical reaction network theory &#171; Hydrobates]]></dc:creator>
		<pubDate>Wed, 06 Oct 2010 08:33:52 +0000</pubDate>
		<guid isPermaLink="false">http://alanrendall.wordpress.com/?p=617#comment-419</guid>
		<description><![CDATA[[...] often include complicated networks of chemical reactions. I have made some comments on this in a previous post. From a mathematical point of view this leads to large systems of ordinary differential equations [...]]]></description>
		<content:encoded><![CDATA[<p>[...] often include complicated networks of chemical reactions. I have made some comments on this in a previous post. From a mathematical point of view this leads to large systems of ordinary differential equations [...]</p>
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		<title>By: Hopf bifurcations and Lyapunov numbers &#171; Hydrobates</title>
		<link>http://alanrendall.wordpress.com/2009/07/24/metabolic-networks/#comment-299</link>
		<dc:creator><![CDATA[Hopf bifurcations and Lyapunov numbers &#171; Hydrobates]]></dc:creator>
		<pubDate>Sun, 10 Jan 2010 13:15:04 +0000</pubDate>
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		<description><![CDATA[[...] There are very many applications where the Hopf bifurcation plays a role. A first example is the Brusselator mentioned above. This is a schematic two-dimensional model for a chemical reactor. When I hear the name I get a mental picture of Brussels sprouts. This is of course nonsense. The name comes from the fact that the model was developed in Brussels and is a simplification of a three-dimensional model called the Oregonator which was developed in Oregon. The latter name was influenced by the fact that it is a kind of oscillator. The Oregonator is nothing other then the Field-Noyes model discussed in a recent post. As mentioned there the Field-Noyes model also exhibits Hopf bifurcations. Hopf bifurcations occur in the FitzHugh-Nagumo and Hogdkin-Huxley systems. Thus they are potentially relevant for electrical signalling by neurons. They may also come up in another kind of biological signalling, namely that by calcium. For an extensive review of this subject I refer to a paper of Martin Falcke (Adv. Phys. 53, 255). In section 5 of that paper the author discusses experimental evidence indicating that certain calcium oscillations cannot be modelled using Hopf bifurcations and that it might be better to use other types of bifurcation. On the other hand he suggests that the evidence for this is not conclusive. Oscillations in glycolysis are modelled by the Higgins-Selkov oscillator, a two-dimensional system bearing a superficial resemblance to the Brusselator. The unknowns are the concentrations of ADP and the enzyme phosphofructokinase. This simple system describing a part of glycolysis exhibits a Hopf bifurcation. More information on this and related systems can be found in the book of Klipp et. al. on systems biology quoted in a previous post. [...]]]></description>
		<content:encoded><![CDATA[<p>[...] There are very many applications where the Hopf bifurcation plays a role. A first example is the Brusselator mentioned above. This is a schematic two-dimensional model for a chemical reactor. When I hear the name I get a mental picture of Brussels sprouts. This is of course nonsense. The name comes from the fact that the model was developed in Brussels and is a simplification of a three-dimensional model called the Oregonator which was developed in Oregon. The latter name was influenced by the fact that it is a kind of oscillator. The Oregonator is nothing other then the Field-Noyes model discussed in a recent post. As mentioned there the Field-Noyes model also exhibits Hopf bifurcations. Hopf bifurcations occur in the FitzHugh-Nagumo and Hogdkin-Huxley systems. Thus they are potentially relevant for electrical signalling by neurons. They may also come up in another kind of biological signalling, namely that by calcium. For an extensive review of this subject I refer to a paper of Martin Falcke (Adv. Phys. 53, 255). In section 5 of that paper the author discusses experimental evidence indicating that certain calcium oscillations cannot be modelled using Hopf bifurcations and that it might be better to use other types of bifurcation. On the other hand he suggests that the evidence for this is not conclusive. Oscillations in glycolysis are modelled by the Higgins-Selkov oscillator, a two-dimensional system bearing a superficial resemblance to the Brusselator. The unknowns are the concentrations of ADP and the enzyme phosphofructokinase. This simple system describing a part of glycolysis exhibits a Hopf bifurcation. More information on this and related systems can be found in the book of Klipp et. al. on systems biology quoted in a previous post. [...]</p>
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		<title>By: Jonathan Vos Post</title>
		<link>http://alanrendall.wordpress.com/2009/07/24/metabolic-networks/#comment-215</link>
		<dc:creator><![CDATA[Jonathan Vos Post]]></dc:creator>
		<pubDate>Sat, 25 Jul 2009 05:53:46 +0000</pubDate>
		<guid isPermaLink="false">http://alanrendall.wordpress.com/?p=617#comment-215</guid>
		<description><![CDATA[The Evolution of Controllability in Enzyme System Dynamics 

http://www.interjournal.org/manuscript_abstract.php?1152005238

Abstract:

A building block of all living organisms&#039; metabolism is the &quot;enzyme chain.&quot; A chemical &quot;substrate&quot; diffuses into the (open) system. A first enzyme transforms it into a first intermediate metabolite. A second enzyme transforms the first intermediate into a second intermediate metabolite. Eventually, an Nth intermediate, the &quot;product&quot; diffuses out of the open system. What we most often see in nature is that the behavior of the first enzyme is regulated by a feedback loop sensitive to the concentration of product. This is accomplished by the first enzyme in the chain being &quot;allosteric&quot;, with one active site for binding with the substrate, and a second active site for binding with the product. Normally, as the concentration of product increases, the catalytic efficiency of the first enzyme is decreased (inhibited). To anthropomorphize, when the enzyme chain is making too much product for the organism&#039;s good, the first enzyme in the chain is told: &quot;whoa, slow down there.&quot; Such feedback can lead to oscillation, or, as this author first pointed out, &quot;nonperiodic oscillation&quot; (for which, at the time, the term &quot;chaos&quot; had not yet been introduced). But why that single feedback loop, known as &quot;endproduct inhibition&quot; [Umbarger, 1956], and not other possible control systems? What exactly is evolution doing, in adapting systems to do complex things with control of flux (flux meaning the mass of chemicals flowing through the open system in unit time)? This publication emphasizes the results of Kacser and the results of Savageau, in the context of this author&#039;s theory. Other publications by this author [Post, 9 refs] explain the context and literature on the dynamic behavior of enzyme system kinetics in living metabolisms; the use of interactive computer simulations to analyze such behavior; the emergent behaviors &quot;at the edge of chaos&quot;; the mathematical solution in the neighborhood of steady state of previously unsolved systems of nonlinear Michaelis-Menton equations [Michaelis-Menten, 1913]; and a deep reason for those solutions in terms of Krohn-Rhodes Decomposition of the Semigroup of Differential Operators of the systems of nonlinear Michaelis-Menton equations. Living organisms are not test tubes in which are chemical reactions have reached equilibrium. They are made of cells, each cell of which is an &quot;open system&quot; in which energy, entropy, and certain molecules can pass through cell membranes. Due to conservation of mass, the rate of stuff going in (averaged over time) equals the rate of stuff going out. That rate is called &quot;flux.&quot; If what comes into the open system varies as a function of time, what is inside the system varies as a function of time, and what leaves the system varies as a function of time. Post&#039;s related publications provide a general solution to the relationship between the input function of time and the output function of time, in the neighborhood of steady state. But the behavior of the open system, in its complexity, can also be analyzed in terms of mathematical Control Theory. This leads immediately to questions of &quot;Control of Flux.&quot;]]></description>
		<content:encoded><![CDATA[<p>The Evolution of Controllability in Enzyme System Dynamics </p>
<p><a href="http://www.interjournal.org/manuscript_abstract.php?1152005238" rel="nofollow">http://www.interjournal.org/manuscript_abstract.php?1152005238</a></p>
<p>Abstract:</p>
<p>A building block of all living organisms&#8217; metabolism is the &#8220;enzyme chain.&#8221; A chemical &#8220;substrate&#8221; diffuses into the (open) system. A first enzyme transforms it into a first intermediate metabolite. A second enzyme transforms the first intermediate into a second intermediate metabolite. Eventually, an Nth intermediate, the &#8220;product&#8221; diffuses out of the open system. What we most often see in nature is that the behavior of the first enzyme is regulated by a feedback loop sensitive to the concentration of product. This is accomplished by the first enzyme in the chain being &#8220;allosteric&#8221;, with one active site for binding with the substrate, and a second active site for binding with the product. Normally, as the concentration of product increases, the catalytic efficiency of the first enzyme is decreased (inhibited). To anthropomorphize, when the enzyme chain is making too much product for the organism&#8217;s good, the first enzyme in the chain is told: &#8220;whoa, slow down there.&#8221; Such feedback can lead to oscillation, or, as this author first pointed out, &#8220;nonperiodic oscillation&#8221; (for which, at the time, the term &#8220;chaos&#8221; had not yet been introduced). But why that single feedback loop, known as &#8220;endproduct inhibition&#8221; [Umbarger, 1956], and not other possible control systems? What exactly is evolution doing, in adapting systems to do complex things with control of flux (flux meaning the mass of chemicals flowing through the open system in unit time)? This publication emphasizes the results of Kacser and the results of Savageau, in the context of this author&#8217;s theory. Other publications by this author [Post, 9 refs] explain the context and literature on the dynamic behavior of enzyme system kinetics in living metabolisms; the use of interactive computer simulations to analyze such behavior; the emergent behaviors &#8220;at the edge of chaos&#8221;; the mathematical solution in the neighborhood of steady state of previously unsolved systems of nonlinear Michaelis-Menton equations [Michaelis-Menten, 1913]; and a deep reason for those solutions in terms of Krohn-Rhodes Decomposition of the Semigroup of Differential Operators of the systems of nonlinear Michaelis-Menton equations. Living organisms are not test tubes in which are chemical reactions have reached equilibrium. They are made of cells, each cell of which is an &#8220;open system&#8221; in which energy, entropy, and certain molecules can pass through cell membranes. Due to conservation of mass, the rate of stuff going in (averaged over time) equals the rate of stuff going out. That rate is called &#8220;flux.&#8221; If what comes into the open system varies as a function of time, what is inside the system varies as a function of time, and what leaves the system varies as a function of time. Post&#8217;s related publications provide a general solution to the relationship between the input function of time and the output function of time, in the neighborhood of steady state. But the behavior of the open system, in its complexity, can also be analyzed in terms of mathematical Control Theory. This leads immediately to questions of &#8220;Control of Flux.&#8221;</p>
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