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Fig. 9.3 Change in flux and
control coefficients as a
function of GLUT isoform
proportions, as predicted by
the model. (a) The glycolytic
flux (
J
) and GLUT flux
control coefficient (
C
J
GLUT
).
(b) HK and glycogen
degradation (
Gly Deg
) flux
control coefficients (
C
J
HK
and
C
J
Gly Deg
) and ATP
concentration. The
lines
indicate proportions of each
GLUT isoform found in cells
under hyperglycemia
(Table
9.3
) and
hypoglycemia (Mar´n-
Hern´ndez
et al. Unpublished results).
f
GLUT3
fraction of GLUT3,
f
GLUT1
fraction of GLUT1
of cancer cells to hypoglycemia, the glycolytic flux increases
20 % with respect
to hyperglycemia, whereas the GLUT flux control coefficient and flux control
distribution remain unchanged (Table
9.2
; Fig.
9.3
). Therefore, this strategy may
seem useful for increasing the glucose uptake without shifting the entire pattern of
enzyme and transporter isoforms, which may in turn lead to ADP and AMP pools
depletion (Table
9.1
; Fig.
9.3
). Furthermore, the results presented enable us to gain
understanding about why cancer cells differentially express multiple glucose
transporters.
9.7 Advances in Modeling OxPhos in Tumor Cells
To decrease ATP levels to promote apoptosis in tumor cells, not only glycolysis has
to be blocked but also OxPhos. In this regard, it has been profusely documented in
recent years that ATP supply by mitochondria is as important as glycolysis for
cancer cells (Moreno-S´nchez et al.
2007
; Sheng et al.
2009
; Chen et al.
2012
). In
fact, cells in solid tumors located far from the blood vessels in which a hypoxic
environment prevails are predominantly glycolytic, whereas cells with a predomi-
nant oxidative (i.e. mitochondrial) metabolism localize closer to blood vessels or
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