"Michael C. Kohn" wrote:
>> >Petr Kuzmic <pkuzmic at biokin.com> wrote in message
[...]
> Of course I do. I was part of the group from 1973 to 1984. Yes David
> did start out with Britton Chance, and initially they did use
> differential analyzers and then analog computers to model time
> courses. However, it was too cumbersome and they abandoned that
> effort.
>> >> It failed, more or less, because the *numerical methods* were not mature
> >> enough then. I wonder what other contributors to this forum think about
> >> the significance of Garfinkel's work.
> >
[...]
>> I dispute the contention that the effort failed.
Perhaps my wording was too strong. I did not mean to imply that the
work of Garfinkel's group was a failure, but rather that they really got
to the limit of what they could do at that time and, as Michael says,
the effort was abandoned. I wonder if anybody has an archival copy of
the software BIOSSIM [sp?, I think for BIOchemical Systems SIMulator]?
It would be interesting to look at that code and see what design ideas
were used.
> [...] The paucity of people with training and experience in
> mathematics as well as biochemistry/physiology caused this field of
> research to be regarded as a mere curiosity and not as something
> others could use.
This, more or less, was the sense in which I used the word "failed",
meaning that Garfinkel's (et al.) computer simulation work did not find
a widespread following.
> [...] Some of the enzymes (e.g. fatty acyl CoA
> synthetase) lost activity when they were purified from the membranes
> in which they were embedded. But these problems are not
> insurmountable, and such effects were represented in the model.
> Today, I am studying metabolic activation of xenobiotic compounds to
> carcinogenic intermediates. Here too, enzyme localization,
> membrane-bound protein complexes, and substrate channeling have
> pronounced effects on the carcinogenicity of an exotic chemical.
Michael, do you have literature references where one could look to see
how the kinetics membrane-bound enzymes in vivo could be handled? Also,
is there a concise way you could describe how the fatty acyl CoA
synthetase was handled, given the fact that it's losing activity outside
the membrane?
-- Petr
_____________________________________________________________________
P e t r K u z m i c, Ph.D. mailto:pkuzmic at biokin.com
BioKin Ltd. * Software and Consulting http://www.biokin.com
