In article <931123132813.~INN-JGAa00559.bionet-news at dl.ac.uk> pjh3142 at rigel.tamu.edu (Pascal Hua) writes:
>> This question might seem easy, but I found it not so obvious as I
>thought about it more:
>> What does rate limiting mean to you ?
>
Rate limitation should be viewed as a quantitative concept.
Metabolic control analysis (MCA), developed in the early 70s, deals with this
problem explicitly. In summary in MCA one uses the flux-control coefficients
which measure the log change in flux after a log change in enzyme
concentration (it is slightly more complex than this but for the moment this
is enough). A flux-control coefficient of 1 (or -1, but ignore this at this
stage) means the enzyme is indeed "rate-limiting" (But please note that at
a steady state ALL enzyme reactions ocurr at the same rate!). However an
inmportant (and exact) result of MCA turned out to be the _summation_theorem_
which says that the sum of the control coefficients of all enzymes towards a
certain (pathway) flux is unity. To cut a long story short most flux-control
coefficients are small, sometimes so small that cannot be properly measured.
THE CONTROL OF A PATHWAY IS A SYSTEM'S PROPERTY AND IS DELOCALIZED THROUGH ALL
THE ENZYMES (in general).
You may be interested in the following references:
SOME REVIEWS
%A Fell, D.A.
%D 1992
%T Metabolic control analysis - a survey of its theoretical and experimental development.
%J Biochem. J.
%V 286
%P 313-330
%A Kacser, H.
%A Porteous, J.W.
%D 1987
%T Control of metabolism: what do we have to measure?
%J Trends Biochem. Sci.
%V 12
%N 1
%P 5
A BOOK WITH MANY CHAPTERS ON THIS TOPIC
%B Control of metabolic processes
%E Cornish-Bowden, A.
%E Cardenas, M.L.
%D 1990
%T Control of metabolism: what do we have to measure?
%I Plenum Press
%C New York
ORIGINAL PAPERS
%A Kacser, H.
%A Burns, J.A.
%D 1973
%T The control of flux.
%J Symp. Soc. Exp. Biol.
%V 27
%P 65-104
%X The original paper.
%A Heinrich, R.
%A Rapoport, T.A.
%D 1974
%T A linear steady-state treatment of enzymatic chains. General properties, control and effector strength.
%J Eur. J. Biochem.
%V 42
%P 89-95
%A Burns, J.A.
%A Cornish-Bowden, A.
%A Groen, A.K.
%A Heinrich, R.
%A Kacser, H.
%A Porteous, J.W.
%A Rapoport, S.M.
%A Rapoport, T.A.
%A Stucki, J.W.
%A Tager, J.M.
%A Wanders, R.J.A.
%A Westerhoff, H.V.
%D 1985
%T Control analysis of metabolic systems.
%J Trends Biochem. Sci.
%V 10
%N 1
%P 16
A SIMPLE BUT BRILLIANT EXPLANATION OF STEADY STATES
%A Higgins, J.
%D 1963
%T Analysis of sequential reactions.
%J Ann. New York Acad. Sci.
%V 108
%P 305-321
%K reflection coefficients, velocity induced, reservoir induced, mixed induced
THIS ONE MIGHT ANSWER PART OF YOUR QUESTION
%A Mazat, J.-P.
%A Jean-Bart, E.
%D 1988
%T How can two steps simultaneously control a flux?
%J Biochem. Ed.
%V 16
%N 1
%P 28-30
Metabolic Control Analysis is one of the main subjects of
bionet.metabolic-reg. You posted in the right group!
Pedro Mendes
prm at aber.ac.uk
PS- I'm sure there will be more replies to this one!
