PMID- 21110941
OWN - NLM
STAT- MEDLINE
DCOM- 20110705
LR  - 20161126
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1807
IP  - 6
DP  - 2011 Jun
TI  - Modeling cancer glycolysis.
PG  - 755-67
LID - 10.1016/j.bbabio.2010.11.006 [doi]
AB  - Most cancer cells exhibit an accelerated glycolysis rate compared to normal 
      cells. This metabolic change is associated with the over-expression of all the 
      pathway enzymes and transporters (as induced by HIF-1alpha and other oncogenes), and 
      with the expression of hexokinase (HK) and phosphofructokinase type 1 (PFK-1) 
      isoenzymes with different regulatory properties. Hence, a control distribution of 
      tumor glycolysis, modified from that observed in normal cells, can be expected. 
      To define the control distribution and to understand the underlying control 
      mechanisms, kinetic models of glycolysis of rodent AS-30D hepatoma and human 
      cervix HeLa cells were constructed with experimental data obtained here for each 
      pathway step (enzyme kinetics; steady-state pathway metabolite concentrations and 
      fluxes). The models predicted with high accuracy the fluxes and metabolite 
      concentrations found in living cancer cells under physiological O(2) and glucose 
      concentrations as well as under hypoxic and hypoglycemic conditions prevailing 
      during tumor progression. The results indicated that HK>/=HPI>GLUT in AS-30D 
      whereas glycogen degradation>/=GLUT>HK in HeLa were the main flux- and ATP 
      concentration-control steps. Modeling also revealed that, in order to diminish 
      the glycolytic flux or the ATP concentration by 50%, it was required to decrease 
      GLUT or HK or HPI by 76% (AS-30D), and GLUT or glycogen degradation by 87-99% 
      (HeLa), or decreasing simultaneously the mentioned steps by 47%. Thus, these 
      proteins are proposed to be the foremost therapeutic targets because their 
      simultaneous inhibition will have greater antagonistic effects on tumor energy 
      metabolism than inhibition of all other glycolytic, non-controlling, enzymes.
CI  - Copyright (c) 2010 Elsevier B.V. All rights reserved.
FAU - Marin-Hernandez, Alvaro
AU  - Marin-Hernandez A
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Mexico D.F. 14080, 
      Mexico.
FAU - Gallardo-Perez, Juan Carlos
AU  - Gallardo-Perez JC
FAU - Rodriguez-Enriquez, Sara
AU  - Rodriguez-Enriquez S
FAU - Encalada, Rusely
AU  - Encalada R
FAU - Moreno-Sanchez, Rafael
AU  - Moreno-Sanchez R
FAU - Saavedra, Emma
AU  - Saavedra E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101124
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 2.7.1.11 (Phosphofructokinase-1)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Biological Transport/physiology
MH  - Carcinoma, Hepatocellular/metabolism/pathology
MH  - Energy Metabolism/physiology
MH  - Enzyme Activation/physiology
MH  - Glucose/pharmacokinetics
MH  - Glycolysis/*physiology
MH  - HeLa Cells
MH  - Hexokinase/metabolism
MH  - Humans
MH  - Liver Neoplasms/metabolism/pathology
MH  - Models, Biological
MH  - *Models, Theoretical
MH  - Neoplasms/enzymology/*metabolism/pathology
MH  - Osmolar Concentration
MH  - Phosphofructokinase-1/metabolism
MH  - Tumor Cells, Cultured
EDAT- 2010/11/30 06:00
MHDA- 2011/07/06 06:00
CRDT- 2010/11/30 06:00
PHST- 2010/06/04 00:00 [received]
PHST- 2010/11/01 00:00 [revised]
PHST- 2010/11/09 00:00 [accepted]
PHST- 2010/11/30 06:00 [entrez]
PHST- 2010/11/30 06:00 [pubmed]
PHST- 2011/07/06 06:00 [medline]
AID - S0005-2728(10)00764-4 [pii]
AID - 10.1016/j.bbabio.2010.11.006 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2011 Jun;1807(6):755-67. doi: 10.1016/j.bbabio.2010.11.006. 
      Epub 2010 Nov 24.