Biology Reference
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Table 9.1 Glycolytic flux and metabolite concentrations obtained from a model developed for
HeLa cells
Model with new isoforms
+GLUT3 +HKI
Control
model a
b GLUT3 + HKI
b GLUT3 + HKI + PFKL
Metabolite
+PFK-L
Glu in
0.7
2.1
0.26
0.81
1.3
1.43
G6P
0.78
1.3
0.85
0.94
1.9
2.2
F6P
0.018
0.031
0.02
0.026
0.046
0.07
FBP
0.14
0.46
0.17
0.13
0.94
0.79
DHAP
2.0
3.5
2.1
1.9
4.9
4.5
G3P
0.08
0.13
0.08
0.07
0.19
0.17
1,3BPG
0.0008
0.003
0.001
0.0008
0.005
0.004
3PG
0.006
0.008
0.006
0.006
0.01
0.009
2PG
0.002
0.004
0.003
0.002
0.004
0.004
PEP
0.0002
0.0003
0.0002 0.0002
0.0004
0.0004
Pyr
2.5
2.56
2.5
2.5
2.6
2.6
ATP
8.3
10.8
8.7
8.1
11.1
10.8
ADP
2.2
0.83
2
2.2
0.65
0.84
AMP
1.3
0.15
1.0
1.4
0.086
0.15
NADH
0.005
0.005
0.005
0.005
0.005
0.005
NAD +
1.34
1.34
1.34
1.34
1.34
1.34
Glycolytic
flux
19.6
27.2
20.9
19.2
32.3
31.5
Metabolite concentrations in mM; flux in nmol lactate min 1 (mg cellular protein) 1 . Metabolite
concentration (mM) fixed values used for modeling were 0.0042 (F2,6BP), 1.7 (citrate), 7.2 (Pi),
33 (lactate), and 5 mM (glucose)
a The control model has GLUT 1, HKII, and PFK1-C. In addition, PFK-1 V max value was
determined in this study (24.7 nmol/min
mg cellular protein). The PFK1-C and PFK1-L
kinetics parameters used in the model were determined at pH 7.5 in the presence of 140 mM K +
and taken from Moreno-S ´ nchez et al. ( 2012 )
b The k value for ATPase was 3.4
10 3 min 1
results from the combination of distinct catalytic capacities from several isoforms.
Figure 9.2 depicts the changes in the pattern of expression for GLUT, HK, and PFK
isoforms in HeLa cells grown under normoxic and hypoxic conditions. Thereby, in
order to account for isoform ratios and their respective kinetic properties, the rate
equations have to be modified accordingly, to more accurately reproduce in silico
the in vivo tumor glycolysis. To reach this goal, the rate equations of the initial
model (Mar ´ n-Hern ´ ndez et al. 2011 ) were modified as detailed below.
The expression for GLUT was modified according to a double mono-substrate
reversible Michaelis-Menten equation ( 9.1 )
0
@
2
4
3
5 þ
2
4
3
5
1
A
½
Glu in
½
Glu in
f 1 Glu out
½
f 2Glu out
½
K eq
K eq
v
¼
V mf
Glu i ½
K Gluin1
Glu i ½
K Gluin2
K Gluout1 1
þ
þ
Glu out
K Gluout2 1
þ
þ
Glu out
(9.1)
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