On Sep 7, 9:21pm, Pedro Mendes wrote:
>> In a previous message I was writing about control analysis and
> channelling. I mentioned one way in which MCA can be applied to
> channelling without any problems in terms of the summation theorem.
> This is the method developed by Boris Kholodenko and Hans Westerhoff
> that uses the elementary reactions of the enzymatic mechanisms.
>> As far as I am aware, the other way to apply MCA to channelling (i.e.
> seeing the two reactions as a single one) that I suggested has never
> been applied. I would be grateful if anyone knows anything to the
> contrary (I reply to Danny Kohl's points about this in a separate
> message)
>>-- End of excerpt from Pedro Mendes
I have used this approach routinely in my large-scale models of intermediary
metabolism in the perfused rat heart. For example, the pyruvate dehydrogenase
and the 2-ketoglutarate dehydrogenase complexes are composed of multiple copies
of three separate enzymes that catalyze the thiamine pyrophosphate-mediated
decarboxylation, acetyl transfer from acetyl CoA, and NAD oxidation of the
enzyme-bound FAD. Because the product of one reaction is passed from the active
site of the enzyme which catalyzed its production to the active site of the
next enzyme in the sequence, under normal conditions the intermediates are
never detected. As a result, the overall reaction catalyzed by the complex
exhibits "3-site ping-pong" kinetics and is treated as a single reaction even
though it is really three reactions. MCA is easily applied to this case.
--
Michael C. Kohn
Laboratory of Computational Biology and Risk Analysis
National Institute of Environmental Health Sciences
P.O. Box 12233, Mail Drop A3-06
Research Triangle Park, NC 27709-2233
Telephone:
919-541-4929 (voice)
919-541-1479 (fax)
e-mail:
kohn at valiant.niehs.nih.gov
WWW home page:
http://valiant.niehs.nih.gov
