Entropy-Enthalpy Compensation

Athel Cornish-Bowden athel at ir2cbm.cnrs-mrs.fr
Wed May 6 08:28:09 EST 1998

Unfortunately I see that on my screen the symbol that I wrote as a degree
sign appears as a zero, so 50C meant 5 degrees C, etc. As this made the
original rather difficult to read I'm sending it all again with the word
"degrees" written out.

I should be interested to know what readers of this news group think about
entropy-enthalpy compensation, i.e. the idea that in natural molecules like
enzymes changes in entropy of reaction (between different molecules doing
the same function) are often compensated for by changes in enthalpy of
reaction. I personally think this is mystical nonsense derived from a
statistical artefact, but there are some distinguished authors who think

I ought to make it clear that I am _not_ referring to thermodynamic
parameters measured calorimetrically. With calorimetric measurement it is
perfectly feasible to measure entropies and enthalpies in such a way that
there is very little statistical correlation between them, and in this case
there is no reason why one should not try to interpret any compensation
effect that one observes. There is a good example in a recent issue of
Biochemistry, in Fig. 3 of the article by Gilli et al. on pp. 5450-5456 of
vol. 37 (1998). They observe that values for deltaS and deltaH for
calmodulin lie roughly on a straight line, with the sort of level of
experimental scatter one might expect. I emphasize that I have _no_quarrel_
either with their view that there is a correlation or with their
interpretation of it. (As it happens some of the authors were in this
laboratory until last year, but that is by chance: I haven't discussed the
work with any of them and the fact that I approve of what they have done is
not connected with the fact that I know some of them).

What I _am_ quarrelling with is the sort of fake correlation that one
observes when the deltaS and deltaH are not independent of one another but
are obtained by measuring an equilibrium (or rate) constant over a range of
temperatures and partitioning the deltaG values obtained into deltaH and
deltaS. The problem with this is that the partitioning involves
extrapolating to 1/T = 0 (or to infinite temperature if you prefer). This
is probably OK in some sorts of chemical studies where the range of
temperatures may be from 100 K to 300 K, but in my view it is emphatically
not OK for the sort of temperature range likely to be used for a protein,
say from 5 degrees C to 40 degrees C, or 278 K to 313 K.

An example of the sort of thing you can get from this sort of measurement
may be found in Fig. 7.5 of Freddie Gutfreund's recent book [Kinetics for
the Life Sciences, pp. 246-248, Cambridge University Press, Cambridge
(1995)], which reproduces data of Johnson & Goldspink in Nature  257,
620-622 (1975). The original authors obtained myofibrillar ATPase from
various fishes living in habitats ranging from the Antarctic to tropical
lakes, at temperatures from about 2 degrees C to about 38 degrees and they
studied the
variation of Vmax with temperature over a range from 0 degrees  to 18
degrees C (they
couldn't go above that because of a discontinuity at 18.5 degrees C) and
deltaH and deltaS of activation, which they plotted against one another.
The result is an excellent straight line with almost no sign of
experimental error, indicating a "compensation temperature" of 18 degrees
C. If we
believe this, it implies that evolution has ensured that both Tipalia
grahami, which spends its life in tropical hot springs at 25-38 degrees C, and
Notothenia rossii, which lives in Antarctic waters at 0-2 degrees C, have
the same
myofibrillar ATPase activity at 18 degrees C, a temperature that neither
fish ever
experiences in normal circumstances (and which is on the other side of a
discontinuity for Tipalia grahami).

There are certainly contributors to this news group more knowledgeable
about thermodynamics than I am. Is anyone able to present this observation
in a way that makes it sound believable?


Email: athel at ibsm.cnrs-mrs.fr
Site map: http://ir2lcb.cnrs-mrs.fr/~athel/sitemap.htm
MCA FAQ: http://ir2lcb.cnrs-mrs.fr/~athel/mcafaq.htm
MCA chapter from my book:


Athel Cornish-Bowden

Laboratoire de Chimie Bacterienne, Centre National de la Recherche
Scientifique, 31 chemin Joseph-Aiguier, B.P. 71, 13402 Marseille Cedex 20,

Phone: + 33 491 16 41 38; fax: + 33 491 71 89 14

Home page: http://ir2lcb.cnrs-mrs.fr/~athel/homepage.htm
(Changed 20 February 1998, but the old URL should continue
to get you there, at least for a few months)

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