Systems Biology Approaches to Cancer Energy Metabolism - Systems Biology of Metabolic and Signaling Networks - page 222

0
@

2
4

3
5

½ P ½

K eq

Q

f 1
Ka 1 Kb

½ A ½ B

v ¼ V mf

½
Ka 1 þ

½
Kb þ

½½
Ka 1 Kb þ

½
Kp þ

½
Kq þ

½½
KpKq þ

½½
Ka 1 Kq þ

½½
KpKb

1 þ

(9.2)

2
4

3
5

1
A

f 2
Ka 2 Kb

½½
K eq

½ A ½ B

þ

½
Ka 2 þ

A ½

Kb þ

B ½

Ka 2 Kb þ

½ A B ½

Kp þ

P ½

Kq þ

Q ½ ½

KpKq þ

P Q ½

Ka 2 Kq þ

½ A Q ½ ½

KpKb

P B

1 þ

2
4

3
5

! 1 !

þ β 1F2 ; 6B P
α 1 Ka F2 ; 6BP1

AT ½
K ATP1

f 1

F2 ; 6 BP

½ ATP

1 þ

1 þ

α 1 Ka F2 ; 6BP1

K ATP1

0
@

1
A

2
4

3
5

3

6 BP
α 1 Ka F2 ; 6BP1

F2 ; 6 BP

α 1 Ka F2 ; 6BP1

F2 ;

F6P 1 þ F6P 1 þ

1

þ

6 BP
Ka F2 ; 6BP1

F2 ; 6BP

Ka F2 ; 6BP1

F2 ;

K F6P1 1 þ K F 6 P 1 1 þ

4 4

2
4

3
5

4

CIT ½
Ki CIT1

ATP ½
Ki ATP1

F2 ; 6 BP

L 11 þ 1 þ F6P 1 þ

α 1 Ka F2

; 6BP1

4 þ 1 þ

F2 ; 6 BP
Ka F2 ; 6BP1

F2 ; 6 BP

K F6P1 1 þ

1 þ

Ka F2

; 6BP1

0 1 1 1

½ FB ½
K ADP K FBP K eq

ADP

@ A A A þ

AD ½
K ADP þ

FB ½
K FBP þ

½ FB ½
K ADP K FBP þ

ADP

1

v ¼ V mf (9.3)

! 1 !

½
K ATP2

ATP

þ β 2F2 ; 6 BP
α 2 Ka F2 ; 6BP2

f 2

½ F2 ; 6 BP

α 2 Ka F2 ; 6BP2

ATP

1 þ

1 þ

K ATP2

0 1

2 3

3

F2 ; 6 BP
α 2 Ka F2

F2 ; 6 BP
α 2 Ka F2

F6P 1 þ F6P 1 þ

@ A

1 4 5

; 6BP2 ; 6BP2

þ

F2 ; 6 BP
Ka F2

F2 ; 6 BP
Ka F2

K F6P2 1 þ K F6P2 1 þ

; 6BP2 ; 6BP2

4 4

2
4

3
5

4

CIT ½
Ki CIT2

ATP ½
Ki ATP2

F2 ; 6BP

L 21 þ 1 þ F6P 1 þ

α 2 Ka F2 ; 6BP2

4 þ þ

1

6BP
Ka F2 ; 6BP2

F2 ;

F2 ; 6 BP
Ka F2

K F6P2 1 þ

1 þ

; 6BP2

0
@

1
A

1
A

1
A

½
K ADP K FBP K eq

½ ADP FBP

AD ½
K ADP þ

FB ½
K FBP þ

½ FB ½
K ADP K FBP þ

ADP

1

Model simulations indicated a marginal increase of 5-13 % in metabolite
concentration, fluxes, and flux control coefficients under normoxic conditions
compared with the model with no different isoforms (Tables 9.4 and 9.5 ). This
result contrasted with the changes observed when GLUT3, alone or in combination
with HKI, replaced GLUT1 (Tables 9.1 and 9.2 ). This behavior can be explained by
the much lower expression of GLUT3 compared to GLUT1 (Fig. 9.2 and
Table 9.3 ).