Bob Phair wrote:
"I am a rank beginner here, but having just read Kacser and Burns (Symp
Soc Exp Biol 27:65-104, 1973) for the first time I am surprised by some
of the responses in this thread."
You may find it useful to refer instead to the reissue of the 1973 as
Kacser et al. (1995) Biochem. Soc. Trans. 23, 341-366. This doesn't try
to rewrite history, so all the bits you quote are still there, but it is
translated into current terminology, and contains additional notes
referring to later developments. It's also (for those who haven't
already tracked down the 1973 paper) a lot easier to find.
"Athel says that in practice close-to-equilibrium reactions have
small-to-negligible flux control coefficients, but that Kacser always
argued that one has no justification for assuming that quasi-equilibrium
steps have very low flux-control coefficients."
"I probably don't yet completely understand the terminology, but if a
flux control coefficient is the same as Kacser's Sensitivity
coefficient, Z, or even if it's the same as his response, R, (=Z*kappa),
then it seems to me Kacser, himself, provided the required proof."
It's the same as the original sensitivity coefficient, or Z. I'm
inclined to agree with you, and have always drawn essentially the same
conclusions from the Disequilibrium section (pp. 83-84) of the 1973
paper as you do. However, Kacser himself always attached far more
importance to the two numbered points ("The step nearest to equilibrium
is not necessarily the least sensitive to control" and "the step most
out of equilibrium is not necessarily the most sensitive to control")
than I would do. I read his "not necessarily" as just that, but I always
felt from talking with him that he meant it more as "not necessarily,
nor even usually". However, I'm basing this more on conversation than on
what the paper says, and others may have different experiences or
interpretations.
"This means ... that for any step close to equilibrium, pi will be
nearly 1 and the corresponding Z will be zero."
Yes, but I think your interpretation of "close to equilibrium" may not
be what he meant. How close is close?
"I've only been part of this newsgroup for a short while, but I already
feel I should have been here years ago."
Glad to have you aboard.
"Perhaps someone will educate me still further, but I found Kacser
eye-opening and profound."
Maybe have a look at vol. 182, No. 3 of J. Theor. Biol. (1996) which is
a special issue in memory of Henrik. It contains quite a lot of stuff
about his life and work, as well as papers on more recent developments.
(A lot of it was available directly on the web, but until I can sort out
the problems with the server that I use for my html files this is not
true at the moment). It may also go some way towards answering your next
question...
"Can anyone tell me something about the intellectual lineage of people
working in this field today? You all seem to know each other well; did
you all train in the same labs?"
There were two principal intellectual sources, created by Henrik Kacser
and Jim Burns in Edinburgh and by the people around Sam Rapoport in
Berlin. Both groups got going independently at about the same time, and
for most of the 1970s their work attracted very little attention (though
a lot of people in the UK knew vaguely about the Edinburgh work, and a
lot of people in the former German Democratic Republic were more
actively conscious of the Berlin work). Their ideas stayed very much on
the sidelines until they were taken up by Joe Tager's group (notably
Bert Groen and Hans Westerhoff) in Amsterdam, who did a great deal to
develop the experimental side and apply the ideas to systems like
oxidative phosphorylation and gluconeogenesis that were of interest to
large numbers of people. (With all due respect to Henrik's memory, not
many biochemists lie awake worrying about how moulds make sure they get
enough arginine, so he tended to get classified as a theoretician to a
greater extent than he really was).
After 1981 there was a massive increase in interest. Take a look at Fig.
2 of my article in J. Theor. Biol. (1996) 182, 195-199, which charts the
citation record of the 1973 paper. Still, this is not to be compared
with real vogue subjects like AIDS, and we are still a smallish group,
mostly located outside the USA, and we tend to know one another even
though it is now probably true that the majority of us never worked in
eith Edinburgh or Berlin.
The question of why metabolic control analysis continues to attract
almost zero interest in the USA continues to be a mystery. Can you shed
any light on this, Bob?
Athel
No home page at the moment...
