PMID- 19681047
OWN - NLM
STAT- MEDLINE
DCOM- 20091113
LR  - 20131121
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 221
IP  - 3
DP  - 2009 Dec
TI  - Kinetics of transport and phosphorylation of glucose in cancer cells.
PG  - 552-9
LID - 10.1002/jcp.21885 [doi]
AB  - Metabolic control analysis of tumor glycolysis has indicated that hexokinase (HK) 
      and glucose transporter (GLUT) exert the main flux control (71%). To understand 
      why they are the main controlling steps, the GLUT and HK kinetics and the 
      contents of GLUT1, GLUT2, GLUT3, GLUT4, HKI, and HKII were analyzed in rat 
      hepatocarcinoma AS-30D and HeLa human cervix cancer. An improved protocol to 
      determine the kinetic parameters of GLUT was developed with D-[2-(3)H-glucose] as 
      physiological substrate. Kinetic analysis revealed two components at low- and 
      high-glucose concentrations in both tumor cells. At low glucose and 37 degrees C, 
      the V(max) was 55 +/- 20 and 17.2 +/- 6 nmol (min x mg protein)(-1), whereas the 
      K(m) was 0.52 +/- 0.7 and 9.3 +/- 3 mM for hepatoma and HeLa cells, respectively. 
      GLUT activity was partially inhibited by cytochalasin B (IC(50) = 0.44 +/- 0.1; 
      K(i) = 0.3 +/- 0.1 microM) and phloretin (IC(50) = 8.7 microM) in AS-30D 
      hepatocarcinoma. At physiological glucose, GLUT1 and GLUT3 were the predominant 
      active isoforms in HeLa cells and AS-30D cells, respectively. HK activity in HeLa 
      cells was much lower (60 mU/mg protein) than that in AS-30D cells (700 mU/mg 
      protein), but both HKs were strongly inhibited by G6P. HKII was the predominant 
      isoform in AS-30D carcinoma and HeLa cells. The much lower GLUT V(max) and 
      catalytic efficiency (V(max)/K(m)) values in comparison to those of G6P-sensitive 
      HK suggested the transporter exerts higher control on the glycolytic flux than HK 
      in cancer cells. Thus, GLUT seems a more adequate therapeutic target.
FAU - Rodriguez-Enriquez, Sara
AU  - Rodriguez-Enriquez S
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia Ignacio Chavez, 
      Tlalpan, Mexico City, Mexico. sara.rodriguez@cardiologia.org.mx
FAU - Marin-Hernandez, Alvaro
AU  - Marin-Hernandez A
FAU - Gallardo-Perez, Juan Carlos
AU  - Gallardo-Perez JC
FAU - Moreno-Sanchez, Rafael
AU  - Moreno-Sanchez R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Glucose Transport Proteins, Facilitative)
RN  - 0 (Insulin)
RN  - 0 (Isoenzymes)
RN  - 3CHI920QS7 (Cytochalasin B)
RN  - 56-73-5 (Glucose-6-Phosphate)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - IY9XDZ35W2 (Glucose)
RN  - S5J5OE47MK (Phloretin)
SB  - IM
MH  - Animals
MH  - Biological Transport/drug effects
MH  - Catalysis/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Cold Temperature
MH  - Cytochalasin B/pharmacology
MH  - Cytosol/drug effects/metabolism
MH  - Female
MH  - Glucose/*metabolism
MH  - Glucose Transport Proteins, Facilitative/antagonists & inhibitors/metabolism
MH  - Glucose-6-Phosphate/pharmacology
MH  - Glycolysis/physiology
MH  - HeLa Cells
MH  - Hexokinase/analysis/metabolism
MH  - Humans
MH  - Insulin/pharmacology
MH  - Isoenzymes/metabolism
MH  - Kinetics
MH  - Mitochondria/drug effects/metabolism
MH  - Neoplasms/*metabolism
MH  - Phloretin/pharmacology
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Wistar
EDAT- 2009/08/15 09:00
MHDA- 2009/11/17 06:00
CRDT- 2009/08/15 09:00
PHST- 2009/08/15 09:00 [entrez]
PHST- 2009/08/15 09:00 [pubmed]
PHST- 2009/11/17 06:00 [medline]
AID - 10.1002/jcp.21885 [doi]
PST - ppublish
SO  - J Cell Physiol. 2009 Dec;221(3):552-9. doi: 10.1002/jcp.21885.