On 14 May 98 at 8:57, Petr Kuzmic wrote:
> Excuse the outsider again for interrupting the experts, but why
> -wouldn't- we "require the knowledge of mechanism" for any biochemical
> system?
Because to determine reaction mechanisms we need a lot of information. The
_in_vivo mechanisms might even not be the ones determined _in_vitro, and
the latter are already difficult to determine.
> A -molecular- system should never be too complex to be described
> successfully in elementary physico-chemical terms (mass action law,
> diffusion, ...).
Petr, I think you could actually give us some arguments contrary to that
view :) Very often kinetic data is not good enough to discriminate between
models, I'm sure you agree with this. Plus, there is always *another*
mechanism that will fit the data. Even the (in)famous Occam's razor does
not say that the simplest mechanism is the TRUE one, just that if we
cannot distinguish them WE ARE BETTER OFF considering the simplest.
So Kacser & Burn's idea is that even when the enzyme mechanisms are not
known there is a lot that we can still say about the regulation of a
metabolic pathway (or any set of chemical reactions and transport steps).
This is what MCA is concerned about. MCA has uncovered
mechanism-independent properties such as the summation theorem (which
holds for any mechanism that the "metabolic units" may follow)
Having said this, MCA and mechanism-based enzymology are not opposed in any
way. If you know the TRUE mechanims of a series of enzymes, that knowledge
should still fit the MCA description.
> What are the most important papers of Kacser's to read,
> and are any of them available electronically?
The majority of his papers are actually very important. But I'd reccomend
reading:
- Kacser, H. & Burns, J.A. (1973) The control of flux. Symp. Soc. Exp. Biol.
27, 65-104
or it's newer version Kacser, H., Burns, J.A. & Fell, D.A. (1995)
The control of flux. Bioc. Soc. Trans. 23, 341-366, available
electronically from
ftp://bmsdarwin.brookes.ac.uk/pub/documents/control_of_flux/
- Kacser, H. & Burns, J.A. (1981) The molecular basis of dominance.
Genetics 97, 639-666.
you can also see Henrik Kacser's full list of papers at
http://ir2lcb.cnrs-mrs.fr/~athel/henrik.htm
to initiate yourself in MCA on the web, you could look at these pages:
http://gepasi.dbs.aber.ac.uk/metab/mca_home.htmhttp://ir2lcb.cnrs-mrs.fr/~athel/mcafaq.htmhttp://ir2lcb.cnrs-mrs.fr/~athel/mcai.htm
Pedro Mendes Inst. Biological Sciences
prm at aber.ac.uk (home: pedro at enzyme.demon.co.uk) Univ. Wales, Aberystwyth,
http://gepasi.dbs.aber.ac.uk/pedro/prmhome.htm Ceredigion SY23 3DD, U.K.
http://gepasi.dbs.aber.ac.uk/softw/gepasi.html FAX: +44 (0)1970 622307
