IUBio

point of regulation

Athel athel at IR2CBM.CNRS-MRS.FR
Fri Apr 25 02:15:09 EST 1997


I was lazy yesterday. In reply to the question "Also, I should
appreciate if anyone can suggest me a detailed book of metabolic
thermodynamics", I said "If you mean a compilation of thermodynamic data
for metabolic reactions I can't suggest anything right off... try the
series of articles that are being produced by Robert Goldberg. I can't
give you a reference from memory..."

I realized during the night it would take me only a minute or two to
find something more useful to say. 

As a recent general reference you could look at Robert A. Alberty (1994)
"Biochemical thermodynamics" Biochim. Biophys. Acta 1207, 1-11. Apart
from being useful in itself, this contains valuable references to other
sources. Likewise IUPAC (1994) "Recommendations for Nomenclature and
Tables in Biochemical Thermodynamics" Pure Appl. Chem. 66, 1641-1666.

The first of the articles by Goldberg is R. N. Goldberg, Y. B. Tewari,
D. Bell, K. Fazio and E. Anderson (1993) "Thermodynamics of
enzyme-catalyzed reactions, Part 1. Oxidoreductases" J. Phys. Chem. Ref.
Data 22, 515-582. There are others in the same journal, and I understand
that eventually all enzymes for which data exist will be covered in the
same journal.

In reply to the first part of Silvina's question, David Fell wrote: 

"This is an argument I detail a bit more in my book (If I can mention a
commercial product in which I have an interest: Understanding the
control of metabolism, Portland Press, 1996). There I also review the
arguments of Jannie Hofmeyr and Athel Cornish-Bowden in favour of the
view that cooperativity in enzymes is more important for metabolite
homeostasis than control of flux (Eur J Biochem 200, 223-236, 1991).
They may wish to respond themselves to your question."

David certainly ought to mention his book, because it is an excellent
introduction, commercial or not. (My review of it will appear in TiBS,
probably in June. It will also appear on the web when TiBS gets around
to sending me the final edited file, as they don't want me to post a
version that is not identical to what will appear in print). Also
excellent, albeit for a much more mathematically sophisticated audience,
is Reinhart Heinrich and Stefan Schuster's book "The Regulation of
Cellular Systems" (Chapman & Hall, 1996), which will be reviewed by me
in Bull. Math. Biol., probably in November. This will also be posted on
the web as soon as our server is fixed.

To take up the point that David suggests I comment on, the idea is that
so far as flux regulation is concerned it makes very little difference
whether there is feedback inhibition or not, and if there is feedback
inhibition it makes very little difference whether this is 
cooperative or not. The story is very different indeed if we look at
metabolite concentrations instead of fluxes, when it becomes extremely
important to have feedback inhibition and for it to be cooperative. It
appears therefore that cooperative feedback inhibition is just as
important as we always thought, but NOT for the reasons (flux
regulation) sometimes suggested. David gives a reference to our 1991
paper. A more recent one coming to similar conclusions in the context of
a more interesting pathway is A. Cornish-Bowden, J.-H. S. Hofmeyr & M.
L. Cardenas (1995) "Strategies for manipulating metabolic fluxes in
biotechnology", Bioorg. Chem. 23, 439-449.

Athel

Home page: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/home_page.html
MCA FAQ: http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/mcafaq.html
MCA chapter from my book:
http://ir2lcb.cnrs-mrs.fr/lcbpage/athel/fek10/mcai.html
(These won't work until our server is fixed. I have no information about
when that will be)




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