Martin Brand wrote:
>> We have measured the control over
> glycolysis in mammalian cells (rat hepatocytes) [see Table 6 in Ainscow, EK
> and Brand MD (1999) Top-down control analysis of ATP turnover, glycolysis
> and oxidative phosphorylation in rat hepatocytes. Eur J Biochem 263,
> 671-685]. The contol over lactate production from glucose 6P (i.e.
> glycolysis) is shared widely, and the enzymes of glycolysis (including PFK)
> have only 0.66 of the control. Other important control points lie in ATP
> consumption (0.47) and oxidative phosphorylation (-0.23).
>> A fuller breakdown of the way this control is exerted [see Fig 1 in
> Ainscow, E.K. and Brand, M.D. (1999) Internal regulation of ATP turnover,
> glycolysis and oxidative phosphorylation in rat hepatocytes. Eur. J.
> Biochem. 266, 737-749] shows the strengths of each of the routes that pass
> regulatory information from different modules to the glycolytic pathway.
>> So in rat hepatocytes the reactions of glycolysis (which include PFK) have
> some control over glycolytic rate, but they are not "effectively
> rate-limiting" in the classical sense.
---
> Dominic-Luc Webb wrote to Athel Cornish Bowden:
> >
> > [...] I know of no argument against PFK as rate limiting step.
---
The combination of the two postings can mean only one thing: Dominic is
working on a doctorate without sufficient knowledge of recent literature
on the topic of his thesis (mathematical modeling of PFK, he says).
This is a very dangerous proposition.
Of course, depending on the circumstances, even ignoring existing
literature may earn a doctorate if the submitted thesis is "politically
correct" in the eyes of the granting committee (just don't question the
rate-limiting step dogma), but in the larger scheme of things such
ignorance won't suffice.
My suggestion to Dominic is to do several things to rectify the
situation:
(1) Use several independent bibliographic databases (Medline, Science
Citation Index, ...) to retrieve published information related to the
mathematical models of PFK.
(2) Devise a reliable method to update this information periodically
(e.g., monthly or even weekly).
(3) To accomplish (1) and (2), it might be wise to consult a science
librarian at Karolinska. At least here in the US, a lot of people
(working as "Reference Librarians") get advanced degrees in Information
Science in order to perform bibliographic searches effectively and
exhaustively.
(4) Establish contacts with people who already published on the topic,
and are knowledgeable in the area. The Usenet newsgroup is one way of
doing that, so welcome and stick around.
Best wishes,
-- 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
P.O. Box 8336 Ph. 608.256.4790
Madison, WI 53708 Fax 608.256.1269
