Jim Reid wrote:
>This is not exactly a serious posting but may be good for some
discussion.
It's a lot more serious than some of the rubbish we've seen recently!
>Recently in "HMSBeagle" their was a discussion on the value of using
model organisms in biology; this lead me to wondering if a similar
concept applies in the study of enzymes or enzyme systems. I am, for
the sake of argument, defining a model a an enzyme (or system) which
has been so extensively studied that arguments relating to that system
are often used a generalization (an example would be (serine)
proteinases in enzyme kinetics). Or alternatively a system which has
permitted or been the forging ground of significant technical advances
(e.g. Hemoglobin, ion-channels and perhaps motor enzymes today).
The serine proteinases are a good illustration of what people do and
also why it may not be a good idea. (I didn't see the HMSBeagle
discussion, so maybe I'm retreading old ground: which issue was it in?)
A whole generation grew up thinking that chymotrypsin was a "typical
enzyme" (whatever that might mean), and in my view this led to a lot of
false generalizations. If we recall that chymotrypsin is small, stable,
extracellular, unspecific and hydrolytic, we can see that it would be
difficult to arrive at any reasonable definition of "typical enzyme"
that would fit it. If we add to that that it is one of the few enzymes
we can imagine life carrying on quite happily without, then...
>What do you think - have advances in enzymology come about through
intense study of a small group of 'zymes? Have any particular enzymes
groups tended to be especially suitable for developing certain
methods?
Yes, and clearly the serine proteinases have led to to a lot of
important knowledge. The above was just to emphasize that we oughtn't
get too carried away. I'm a little surprised at how much research STILL
gets done on enzymes like chymotrypsin now that methods are available
for studying more interesting enzymes.
>In MCA have certain pathways been studied more extensively than
others? Given that that is the case (-Grin-) is this as experimental
data is more widely available for some paths than others, or that they
are more experimentally accessable, or theoretically tractable?
Now to the real question. By far the greatest difficulty that faces
anyone interested in modelling metabolic pathways is the almost total
absence of usable experimental data. In the past one could have said
that the computer programs weren't up to handling any serious data, but
that is far from true now. Programs like Gepasi
(http://gepasi.dbs.aber.ac.uk/softw/gepasi.html) or SCAMP
(http://www.fssc.demon.co.uk/Scamp/scamp.htm) are capable of handling
any pathway for which reasonable data exist. However, you need:
(1) Data for ALL the steps in the pathway, including
(2) kinetic equations for BOTH forward AND reverse reactions,
(3) in the presence of ALL relevant metabolites,
(4) preferably determined under consistent conditions.
How many pathways are there for which even a rough approximation to
these requirements is satisfied? Thanks to the heroic work of the group
of Fred Opperdoes in Brussels the glycolytic pathway in
<italic>Trypanosoma brucei</italic> is one (see
http://ir2lcb.cnrs-mrs.fr/~athel/eise.htm or
http://ir2lcb.cnrs-mrs.fr/~athel/eise2.htm). What others are there?
Athel
Email: athel at ibsm.cnrs-mrs.fr
Site map: http://ir2lcb.cnrs-mrs.fr/~athel/sitemap.htm
New Beer in an Old Bottle:
http://ir2lcb.cnrs-mrs.fr/~athel/buchner.htm
MCA FAQ: http://ir2lcb.cnrs-mrs.fr/~athel/mcafaq.htm
MCA chapter from my book:
http://ir2lcb.cnrs-mrs.fr/~athel/mcai.htm
