Michael Kohn (kohn at VALIANT.NIEHS.NIH.GOV) wrote:
: Ascites tumor cells are found in the hypoxic environment of the peritoneal
: fluid and are largely dependent on glycolysis for energy production. The tissue
: capacity of hexokinase is quite low in these cells, and addition of hexokinase
: increases the glycolytic rate (J. Biol. Chem. 256, 8699, 1981). However, others
: (J. Biol. Chem. 258, 3702, 1983) suggested that glycolysis in these cells was
: limited by the ability of Na,K-ATPase to regenerate the Pi consumed at
: glyceraldehyde phosphate dehydrogenase. My application of metabolic control
: theory (MCT) to a detailed model of ascites cell glycoclysis indicated that
: nearly all the control is distributed among the four kinases of the pathway,
: suggesting that glycolysis is coherently regulated by the phosphate potential,
: just as we were taught in elementary biochemistry class. I also modeled aerobic
: metabolism in the perfused rat heart and analyzed the model with MCT. This
: exercise indicated that glycolytic control was distributed among those enzymes
: (including the mitochondrial respiratory enzymes) which produce or consume ATP.
: This reinforces the concept that glycolysis is coherently regulated by the
: phosphate potential, which, in turn, is controlled by the enzymes involved in
: adenine nucleotide metabolism. Among the cytosolic enzymes, phosphofructo-1-
: kinase, pyruvate kinase, and creatine kinase were the major controllers. It
: seems to me that searching for a single rate-limiting step in a metabolic
: pathway is a futile effort when the constituent enzymes share regulatory
: cofactors.
Interesting. However, both example cited are mammalian cells. I wonder
how universial is the conclusion that the control of glycolysis is
distributed among the kinases in the pathway. Anyone knows of other
examples? Or maybe we can ask the question the other way round. How much
do we have to tweak the system so that the control is no longer
distributed among the kinases?
--
Ing-Nang Wang
Dept. Ecology and Evolution
SUNY-Stony Brook
ingnang at life.bio.sunysb.edu
