As a second fundamental reaction, the reaction catalyzed by
GAPDH was identified in both cell lines. This is vital for the
glycolytic route because this is where the first high energy com-
pound is formed. It is responsible for the conversion of glyceralde-
hyde-3-phosphate to 1,3-bisphosphoglycerate coupled with
reduction of NAD+ to NADH. It is catalyzed by the enzyme
GAPDH which is considered unique and special because it has
the ability to bind to NAD+or NADH and sometimes to DNA
and RNA [116].
In addition to the role it plays in energy metabolism, GAPDH
has other functions independent of glycolysis; these include cyto-
skeletal regulation, endocytosis, membrane fusion, tRNA trans-
port, and DNA replication and repair [117].
Its overexpression in several types of tumors, such as breast
cancer, as well as the gene that produces it, is associated with the
activity of the HIF-1αtranscription factor, as recently reported
by [118].
Data suggest that GAPDH may play an important role in
promoting metastasis, at least in colon cancer. At the molecular
level, GAPDH seems to physically interact with Sp1, a key tran-
scriptional factor known to bind to the promoter of SNAIL and
enhance its expression. It seems possible that GAPDH forms a
protein complex with Sp1 and enhances to expression of SNAIL,
which is a transcriptional inducer of epithelial-mesenchymal
transition [119].
The enolase catalyzed reaction (ENO), also identified as funda-
mental, shows similar proportions in theS_ifor both conditions and
in the two cell lines. However, their absolute values differ consider-
ably (HeLa: normoxia: 0.777 [J/K min]10^3 , hypoxia:
1.155 [J/K min]10^3. This is an enzyme that is highly conserved
and its three isoforms (α, β, and γ) show very few kinetic
differences [120].
According to one analysis [121] the isoformα, present primar-
ily in fetal cells, is overexpressed in human liver carcinomas and the
gene encoding it is one of the targets of HIF-1. The importance of
this enzyme for the development of cancer is that it is capable of
acting as a plasminogen receptor 6, favoring the growth and dis-
semination of tumor cells [87].
The reaction catalyzed by Hexokinase (HK, reaction # 2) is
identified as one of the fundamental in glycolytic pathways by the
calculation of the entropy production rate and is one of the bio-
chemical checkpoints. In this reaction, glucose is activated for the
following reactions by phosphorylation producing glucose 6 phos-
phate, with ATP as a phosphate donor [111].
HK is a limiting enzyme (control point) of the flow along the
route. There are four isoforms present in mammals, HK2 expres-
sion is markedly induced in cancer cells by multiple mechanisms152 Sheyla Montero et al.