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<h1 class="top">Metabolic control analysis <abbr class="deja" title="Frequently asked questions">FAQ</abbr>
</h1>
<p class="header">This page is the first of four containing a list of frequently asked questions (FAQ)
about metabolic control analysis.</p>
<h2>Introduction</h2>
<p>This page is intended as an elementary introduction to metabolic control
analysis for people who have heard of metabolic control analysis but have very
little idea of what it is. If you need something more advanced you should try
Pedro Mendes’s <a href="http://dbkgroup.org/mca_home.htm">
<abbr title="Metabolic control analysis">MCA</abbr>
Web</a>, the web version of
<a href="mca0.htm">Chapter 12</a> of
<a href="fek.htm"><cite>Fundamentals
of Enzyme Kinetics,</cite></a> (3rd edition, 2004). Many of the answers give links to
more detailed information to be found on other pages. Strictly the title FAQ
(<q>frequently asked questions</q>) may be a misnomer, as really I have little idea
of how often some of these questions are asked; the page is more an attempt to
answer the sort of questions I would ask if I were new to the subject.
Suggestions for additional questions will be welcome, as will comments,
corrections, etc. to the answers that are listed.
<p>Although the questions are grouped approximately according to subject matter,
the answers are deliberately listed in an arbitrary order. This is to encourage
browsing, as in an reference book, where one sometimes discovers information by
chance that is much more interesting than the answer to the question that
provoked taking the book off the shelves in the first place.
<h2><a name="index"></a>Index</h2>
<ul>
<li><em>Theoretical analysis of metabolic control</em><br><br>
<ul>
<li><a href="#whatmca">What is metabolic control analysis?</a>
<li><a href="#whyignore">Why does metabolic control analysis appear to ignore
enzyme mechanisms?</a>
<li><a href="mcafaq2.htm#fot">What is flux-oriented theory?</a>
<li><a href="mcafaq4.htm#bst">What is biochemical systems theory?</a>
<li><a href="#sensy">How is metabolic control analysis related to sensitivity analysis?</a>
<li><a href="mcafaq2.htm#topdown">What is the top-down approach to metabolic control analysis?</a>
</ul>
<li><em>Terminology and results of control analysis</em><br><br>
<ul>
<li><a href="mcafaq3.htm#local">What are local and system properties?</a>
<li><a href="mcafaq2.htm#elasticity">What is an elasticity?</a>
<li><a href="#elycoef">What is an elasticity coefficient?</a>
<li><a href="mcafaq3.htm#whyely">Why <q>elasticity</q> (rather than, say, <q>order of reaction</q>)?</a>
<li><a href="mcafaq4.htm#cocf">What is a control coefficient?</a>
<li><a href="mcafaq3.htm#summ">What are the summation relationships?</a>
<li><a href="mcafaq4.htm#chan">How does channelling affect the summation relationships?</a>
<li><a href="#conny">What is the connectivity relationship?</a>
<li><a href="mcafaq3.htm#respco">What is a response coefficient?</a>
<li><a href="mcafaq2.htm#partition">What is the partitioned response relationship?</a>
<li><a href="mcafaq4.htm#enzconc">Is it true that metabolic control analysis assumes that enzymes are
regulated solely by changing their concentrations (or <i>V</i> values)?</a><br><br>
</ul>
<li><em>Metabolic modelling</em><br><br>
<ul>
<li><a href="mcafaq3.htm#whymodel">What advantages does modelling have over algebraic analysis?</a>
<li><a href="mcafaq2.htm#howmodel">What programs are available for metabolic modelling?</a><br><br>
</ul><br>
<li><em>Older terminology</em><br><br>
<ul>
<li><a href="#whatmct">What is metabolic control theory (and is it different from metabolic control analysis)?</a>
<li><a href="mcafaq2.htm#sens">What is a sensitivity?</a>
<li><a href="mcafaq2.htm#concof">What is a controllability coefficient?</a>
<li><a href="mcafaq2.htm#cstrength">What is a control strength?</a><br><br>
</ul>
<li><em>Control and regulation</em><br><br>
<ul>
<li><a href="mcafaq4.htm#regn">How is metabolic control analysis related to classical ideas of metabolic regulation?</a>
<li><a href="mcafaq2.htm#feedback">How does feedback inhibition affect the distribution of flux control in a pathway?</a><br><br>
</ul>
<li><em>Uses of control analysis</em><br><br>
<ul>
<li><a href="mcafaq2.htm#mainq">What are the main questions that metabolic control analysis sets out to answer?</a>
<li><a href="mcafaq2.htm#biotech">How can yields of metabolic processes be improved for biotechnological purposes?</a>
<li><a href="mcafaq3.htm#myopath">How does metabolic control analysis aid in understanding
mitochondrial myopathies and other metabolic diseases?</a>
<li><a href="mcafaq4.htm#recess">How does metabolic control analysis explain the fact that
most mutations in diploid organisms are recessive?</a><br><br>
</ul>
<li><em>Sources of information</em><br><br>
<ul>
<li><a href="#netdetails">Where can I find more detailed information on the web?</a>
<li><a href="mcafaq4.htm#publdetails">Where can I find more detailed information in the
printed literature?</a>
<li><a href="mcafaq2.htm#mcaboox">Are there any books devoted to metabolic control analysis?</a>
<li><a href="mcafaq3.htm#mcameetings">Where can I find information about meetings related
to metabolic control analysis?</a>
</ul>
<li><em>Other</em><br><br>
<ul>
<li><a href="mcafaq2.htm#whynot">Why is the question that interests me not listed?</a>
</ul>
</ul>
<h3 class="framed"><a name="whatmca"></a>What is metabolic control analysis?</h3>
<div class="sidebar-vsmall"><p class="in-sidebar"><a href="mcafaq.htm#index">Index</a></div>
<p>Metabolic control analysis is a method for analysing how the control of fluxes
and intermediate concentrations in a metabolic pathway is distributed among the
different enzymes that constitute the pathway. Instead of assuming the
existence of a unique rate-limiting step, it assumes that there is a definite
amount of flux control and that this is spread quantitatively among the
component enzymes. Metabolic control analysis was formerly (and is sometimes
still) known as metabolic control theory, and is closely related to the
engineering discipline known as <a href="#sensy">sensitivity analysis</a>.
Alternative approaches to studying the kinetic behaviour of multi-enzyme
systems are <a href="mcafaq2.htm#fot">flux-oriented theory</a> and
<a href="mcafaq4.htm#bst">biochemical systems theory</a>.
<h3 class="framed"><a name="conny"></a>What is the connectivity relationship?</h3>
<div class="sidebar-vsmall"><p class="in-sidebar"><a href="mcafaq.htm#index">Index</a><br>
<a href="mca6.htm#1">more...</a></div>
<p>For any metabolite and any flux in a system, one can multiply the flux
<a href="mcafaq4.htm#cocf">control coefficient</a> of an enzyme by its
<a href="mcafaq2.htm#elasticity">elasticity</a> with respect to the metabolite concerned.
If one does this for all of the enzymes in the system and adds all the
resulting products, they give a sum of zero. This is the general form of the
connectivity relationship.
<p> For metabolites that have non-zero elasticities for numerous enzymes (i.e.
for metabolites that influence the activities of numerous enzymes) the
resulting sum contains many terms and is not particularly useful. However, if a
metabolite influences only two enzymes, as for example the enzyme that produces
it and the enzyme that consumes it, it will have only two non-zero
elasticities, and the sum will contain only two terms, each of which must then
be minus the other. In this case the connectivity relationship becomes much
more useful, as it provides a way of calculating an unknown
<a href="mcafaq4.htm#cocf">control coefficient</a> from a known one, provided the relevant
elasticities are also known.
<h3 class="framed"><a name="elycoef"></a>What is an elasticity coefficient?</h3>
<p>An elasticity coefficient is exactly the same as an
<a href="mcafaq2.htm#elasticity">elasticity</a>; both terms are used.
<h3 class="framed"><a name="whatmct"></a>What is metabolic control theory (and is it different
from metabolic control analysis)?</h3>
<p>Metabolic control theory is an older term for metabolic control analysis. It is
still used by some authors, but started to fall into disuse at the end of the
1980s when some authors began to emphasize that metabolic control analysis is
more a method for analysing how control is distributed than a body of theory as
such.
<h3 class="framed"><a name="sensy"></a>How is metabolic control analysis<br>related to sensitivity analysis?</h3>
<p>Sensitivity analysis is a technique in engineering that shares much of the
mathematics and concepts of metabolic control analysis. The
<a href="mcafaq4.htm#cocf">control coefficients</a> of metabolic control analysis are, in
effect, sensitivities as understood by engineers.
<br>
<h3 class="framed"><a name="whyignore"></a>Why does metabolic control analysis appear to<br>
ignore enzyme mechanisms?</h3>
<div class="sidebar-vsmall"><p class="in-sidebar"><a href="mcafaq.htm#index">Index</a></div>
<p>Metabolic control analysis tends to treat the kinetic properties of the
component enzymes as a black box. Some authors have been very critical of this,
suggesting that shedding light on mechanism is the only reason for studying
kinetics in the first place. However, in reality it is the usual kind of
abstraction one finds (and needs) at all level of science. Although wave
mechanics is at the basis of all chemistry, it is hardly possible to present a
list of typical reactions of aldehydes, for example, in terms of wave equations.
Even if it were possible it would not be helpful because it would hide the
points of immediate interest in a lot of algebra. At another level, all
interactions between living organisms are dependent on the laws of chemistry,
but again, it would be neither possible nor, if it were possible, helpful to
discuss the political relationships between countries in terms of chemical
reactions. Studies of biochemical kinetics have been dominated for nearly a
century by an interest in molecular mechanisms, but for understanding how whole
pathways behave it has been found useful to decrease the emphasis on mechanism.
Thus mechanisms such as cooperative <a href="mcafaq2.htm#feedback">feedback inhibition</a>
are not ignored in metabolic control analysis, but they are given less emphasis
than in classical studies of metabolic regulation.
<h3 class="framed"><a name ="netdetails"></a>Where can I find more detailed information on the web?</h3>
<div class="sidebar-vsmall"><p class="in-sidebar"><a href="mcafaq.htm#index">Index</a></div>
<p>Some possibilities are as follows:
<ul>
<li>Pedro Mendes’s
<a href="http://dbkgroup.org/mca_home.htm">MCA Web</a>
<li>The web version of <a href="mca0.htm">Chapter 12</a> of
<a href="fek.htm"><cite>Fundamentals of Enzyme Kinetics</cite></a> (3rd edition, 2004).
<li>Douglas Kell’s <a href="http://www.bio.vu.nl/grc2000/bibliography.html">Canon
of reviews on metabolic organization, channelling and control</a>
</ul>
<p>
<br><br>
<p>
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Page created before 1998<br>
Last update: 22 December 2008<br>
Last significant update: 18 April 2007<br>
Comments and corrections to this page are welcome, and may be sent to <a href="mailto:athel@ibsm.cnrs-mrs.fr">Athel Cornish-Bowden</a>.<br>
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