Paul Schlosser wrote:
"Well in many cases the drugs are designed to inhibit metabolism,
and for that you can pick *any* enzyme in the pathway, provided
that the inhibition is strong enough. So there isn't much of a
need to identify the control coefficients."
This is true enough, but "provided that the inhibition is strong enough"
is a much bigger proviso than it sounds, because it is only really true
if the inhibitor binds *much* (say a thousandfold) more tightly than the
substrate, which means that one is unlikely to find such an inhibitor by
looking at substrate analogues. Why does it have to bind so tightly?
Because "competitive" works both ways: if the inhibitor can compete with
the substrate then the substrate can compete with the inhibitor; this in
turn means that if the inhibitor is added at a concentration equal to
its inhibition constant then constant flux can be reestablished by
raising the substrate concentration by a mere factor of two. To achieve
significant effects with competitive inhibitors either their
concentrations have to be unrealistically huge or they have to have
extremely low inhibition constants. I discussed this in more detail in
FEBS Lett. 203, 3-6 (1986).
Benno ter Kuile wrote:
"In short, we must blow our own trumpets forcefully. I like to abuse
this opportunity by doing so and announce that a seminar on the
"Regulation of energy metabolism" will be held at the coming General
Meeting of the American Society of Microbiology (May 4-8, Miamy Beach).
A large attendance may convince the powers that be that the study of
energy metabolism is still considered worthwile."
Is any more information about this seminar available? For example, is
there a web site?
Regards,
Athel
