At 07:30 24/04/97 -0700, Maria Silvina Fornasari wrote:
>Could anyone tell me why the principal regulatory steps (presence of
>allosteric enzymes) in metabolic pathways are irreversible paths
>(DeltaG0<<0)?
The easy answer is to put this the other way round: why are irreversible
reactions regulated? Then it can be seen that the danger of an
irreversible reaction that is not regulated is that it will allow its
products to accumulate towards the equilibrium position, which would be
disadvantageous because of the osmotic implications, apart from tying up
large amounts of matter in a few compounds and slowing down the rate of
metabolic transitions.
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.
As an illustration, genetically manipulated organisms where the amount of
phosphofructokinase has been greatly increased, or where it has been
replaced by an enzyme with altered or no allosteric responses, show more
changes in metabolite concentrations than flux (e.g. Thomas, S et al,
Biochem. J., 322, 111-117 & 119-127, 1997).
Be warned though that this is hardly the conventional text book view.
David Fell
=======================================================
David Fell, daf at bms.brookes.ac.uk (usual & current)
GESBI, UFR de Biochimie, Universite de Bordeaux II, 146 rue Leo Saignat,
33076 Bordeaux CEDEX, FRANCE.
David.Fell at u-bordeaux2.fr (April-June '97)
