Dominic-Luc Webb said:
>It appears the reason for the confusion about
whether PFK is rate limiting depends on the
cell type. The nay sayers are citing yeast
and trypanosomes, while I am focused on mammalian
PFK studies, largely in skeletal muscle and
pancreatic beta cells. In the latter case, it
appears to remain valid that PFK is effectively
rate limiting.
The situation in at least one mammalian cell is not different in general
terms to that in trypanosomes and yeast. 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.
Martin Brand
Dr Martin Brand
MRC Dunn Human Nutrition Unit
Hills Road
Cambridge CB2 2XY
UK
Phone Office +44 1223 252800
Phone Lab +44 1223 252806
Fax +44 1223 252805
www.mrc-dunn.cam.ac.uk
---
