Systems Biology (Methods in Molecular Biology)

In Fig.11 it is observed that the reactions that show a highS_i

variation in the range of 2.5–25 mM of glucose were GLUT,

MCT1, HK, GADPH y PYK. This behavior is related to the capac-

ity of these proteins to change their flow in this range, in other

words, an increase in their reaction rate and in consequence an

increase in the entropy production rate (seeEq. ( 8)).

The reactions GLUT and HK exhibit high values ofS_ifor the

glucose concentrations of 25 mM in the three phenotypes (see

Fig.11). This behavior was corroborated by the results of the

studio of the sensibility analysis. Sensitivity analysis [140] quantita-

tively investigates the behavior of a system as a response to changes

in parameter values.

The transporter GLUT 1 performs a fundamental roll in many

steps of cancer progression. It has been demonstrated that GLUT1

may regulate proteins that play a role in early tumor growth as well

as in cancer invasiveness and metastasis [145].

Several studies demonstrate that hexokinase, particularly the

Type II isoform (HK II), plays a critical role in initiating and

maintaining the high glucose catabolic rates of rapidly growing

tumors. Thus, it appears that hexokinase and its association with

mitochondrial protein complex may play important roles in the

essential homeostatic processes such as glucose metabolism and

apoptosis. The inhibition of HK has significant effects in the metab-

olism and cell survival [116].

4.3 The Return
of Oscillations: Cancer
Glycolysis Model

At macroscopic scales, the self-organization and the complexity

exhibited by dynamic systems are manifested through oscillations

sustained in time and/or space. In biological systems these oscilla-

tions are usual [146], and they not only guarantee robustness, but

also allow the system to perform several functions, including con-

trol and regulation.

Oscillations in yeast metabolism are well documented in the

literature [146]. However, to the best of our knowledge, there are

Fig. 11Entropy production rate normalized values for reactions that show a high

variation in the range of 2.5–25 mM of glucose

158 Sheyla Montero et al.