Evaluation of the Coordinated Control of
Activated Glycolysis and Respiration by Orthophosphate
and ADP in Ascites Tumor Cells
E. L. COE, MARY H. COE, and IN-YOUNG LEE
With 2 Figures
Abstract
During the first minute after addition of glucose to respiring ascites tumor cells,
there are two internally regulated glycolytic units: hexokinase through phosphofructokinase; and triosc-P dehydrogenase through lactate dehydrogenase. The
velocity of the former, VPFK, and of the latter VLDH, as well as the velocities of
respiration and A TP hydrolysis are linear functions of both ADP and intracellular
Pi. Expressions for d/dt(ADP) and d/dt(Pi) are solved for ADP, assuming various
combinations of ADP and Pi dependence for the velocities. Comparisons of theoretical and experimental ADP curves indicate that neither ADP nor Pi control both
VPFK and VLDH, but that Pi probably controls VPFK while ADP controls VLDH.
Velocities of glycolytic enzymes and of respiration in EHRLICH ascites
carcinoma cells have been correlated previously with intracellular ADP and
Pi concentrations [3]. During the first minute after glucose addition, glycolysis divides into two internally regulated segments: the "head end" including hexokinase through phosphofructokinase; and the "tail end", from
triose-P dehydrogenase through lactate dehydrogenase [1]. The intermediate
segment, aldolase and triose-P isomerase, appeared to equilibrate fructose
diphosphate and the triose phosphates without much effect on either the
head or tail. The velocity of the phosphofructokinase step, V PFK , was
chosen to represent the head, and that of lactate dehydrogenase, V LDH , the
tail, since all enzymatic rates within a segment are nearly equivalent. The
velocities of respiration, V R, and of overall A TP hydrolysis, V s , as well
as V PFK and V LDH are shown as functions of ADP and esterified phosphate
(Pest) in Fig. 1, for a representative experiment (Exp. A., ref. [3]). Assuming a slow rate of extracellular Pi entry [4] intracellular Pi = (C-Pest),
where C is the initial intracellular concentration [3]. Vs is calculated from
the combined theoretical ATP yield of glycolysis and respiration [1, 2]. All
the velocities are approximately linear functions of both ADP and, by
deduction, intracellular Pi from 10-60 sec. Hence, further considerations
are necessary to separate ADP from Pi dependency.
Activated Glycolysis and Respiration by Orthophosphate
and ADP in Ascites Tumor Cells
E. L. COE, MARY H. COE, and IN-YOUNG LEE
With 2 Figures
Abstract
During the first minute after addition of glucose to respiring ascites tumor cells,
there are two internally regulated glycolytic units: hexokinase through phosphofructokinase; and triosc-P dehydrogenase through lactate dehydrogenase. The
velocity of the former, VPFK, and of the latter VLDH, as well as the velocities of
respiration and A TP hydrolysis are linear functions of both ADP and intracellular
Pi. Expressions for d/dt(ADP) and d/dt(Pi) are solved for ADP, assuming various
combinations of ADP and Pi dependence for the velocities. Comparisons of theoretical and experimental ADP curves indicate that neither ADP nor Pi control both
VPFK and VLDH, but that Pi probably controls VPFK while ADP controls VLDH.
Velocities of glycolytic enzymes and of respiration in EHRLICH ascites
carcinoma cells have been correlated previously with intracellular ADP and
Pi concentrations [3]. During the first minute after glucose addition, glycolysis divides into two internally regulated segments: the "head end" including hexokinase through phosphofructokinase; and the "tail end", from
triose-P dehydrogenase through lactate dehydrogenase [1]. The intermediate
segment, aldolase and triose-P isomerase, appeared to equilibrate fructose
diphosphate and the triose phosphates without much effect on either the
head or tail. The velocity of the phosphofructokinase step, V PFK , was
chosen to represent the head, and that of lactate dehydrogenase, V LDH , the
tail, since all enzymatic rates within a segment are nearly equivalent. The
velocities of respiration, V R, and of overall A TP hydrolysis, V s , as well
as V PFK and V LDH are shown as functions of ADP and esterified phosphate
(Pest) in Fig. 1, for a representative experiment (Exp. A., ref. [3]). Assuming a slow rate of extracellular Pi entry [4] intracellular Pi = (C-Pest),
where C is the initial intracellular concentration [3]. Vs is calculated from
the combined theoretical ATP yield of glycolysis and respiration [1, 2]. All
the velocities are approximately linear functions of both ADP and, by
deduction, intracellular Pi from 10-60 sec. Hence, further considerations
are necessary to separate ADP from Pi dependency.