(For some reason the message I sent with this title on 6th August
disappeared without trace. I sent it again on 19th August, thinking it
would be nice to have at least one relevant posting this month, but
this was rejected by the system with a silly message ("Warning 400 No
space left on device writing article file -- throttling -- Article will
be spooled. Can't create spool file, Permission denied", though it
didn't reject the miniFAQ and Fundraiser, nor has it rejected several
junk messages this month). Now I'm trying again.)
A reader of my MCA-FAQ pages
(http://ir2lcb.cnrs-mrs.fr/~athel/mcafaq.htm) has asked me to address
the question "Why does metabolic channeling invalidate the summation
theorem?". I have drafted the following response, but I should be
grateful for the expert opinions of contributors to this group as to
whether it adequately covers the point (within the constraint that
questions and answers in these pages are intended to be brief):
How does channelling affect the summation relationships?
The term <italic>channelling</italic> refers to mechanisms in which
the
product of one enzyme is transferred directly to an enzyme that uses
it
as substrate without necessarily passing through the free solution.
This implies the existence of a complex between the two (or more)
enzymes involved, a <italic>static complex</italic> if it has a long
life time and exists independently of whether the reaction is
proceeding, or a <italic>dynamic complex</italic> if it is formed
transiently during the catalysis. In either case increasing the
concentration of one component enzyme of the complex affects the
concentrations both of the free component and those of any complexes
that it forms with other enzymes. As these various different species
may have different kinetic constants for the reactions in which they
are involved the rate of the reaction catalysed by the enzyme whose
total concentration is varied will not be proportional to that
concentration.
As long as the summation relationships are expressed in terms of
control coefficients that refer to the independent catalysts, in
accordance with modern practice, they are not affected by channelling.
As it is no longer true that the individual rates are proportional to
the concentrations of the individual enzymes, however, the summation
relationships no longer apply if the control coefficients refer to
enzyme concentrations rather than catalytic activities. With static
complexes the deviations may be large, but with dynamic complexes they
still usually apply approximately.
----
Any comments?
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 chapter from my book: http://ir2lcb.cnrs-mrs.fr/~athel/mcai.htm
ARW on Control Analysis (Visegrad, Hungary, April 1999):
http://ir2lcb.cnrs-mrs.fr/~athel/meet99.htm
