[PDF][PDF] The Role of Glucose 6-Phosphate in the Regulation Glucose Metabolism in Human Erythrocytes

IARAED EDWM, DL O'CONNELL - J. biol. Chem, 1964 - academia.edu
IARAED EDWM, DL O'CONNELL
J. biol. Chem, 1964academia.edu
(Received for publication, June 14, 1963)* it concentrations of glucose ranging from the
physiological (1) to very high values (2), the rate of equilibration of external glucose with
human red cells is much greater than the rate of glucose utilization by cellular reactions, the
first of which is thought to be hexokinase. In mammalian tissues glucose 6-phosphate may
undergo the following fates: return to glucose via phosphatase action, passage into
glycogen, or entry into the energy-yielding Embden-Meyerhof path or into the 6 …
(Received for publication, June 14, 1963)
* it concentrations of glucose ranging from the physiological (1) to very high values (2), the rate of equilibration of external glucose with human red cells is much greater than the rate of glucose utilization by cellular reactions, the first of which is thought to be hexokinase. In mammalian tissues glucose 6-phosphate may undergo the following fates: return to glucose via phosphatase action, passage into glycogen, or entry into the energy-yielding Embden-Meyerhof path or into the 6-phosphogluconate path. Of these only the last two are reported to be of importance in the human red cell, since glycogen is apparently not present (3) nor are other important storage materials. The possibility that a phosphatase acting on glucose-6-P may function in situ has not been resolved. In mature erythrocytes, the amounts of glucose-6-P entering the Embden-Meyerhof path or the oxidative pathway are readily assessed since there esists no pathway for the oxidation of pyruvate to CO,(4). Under conditions of steady state, the rate of metabolism of glucose will be equal to the rate of net flow from glucose to glucose-6-P, which is determined by the relative rates of two irreversible steps, the kinase and phosphatase. In the mature red cell, with glycolysis the major source of adenosine triphosphate, it would be forbidden to have either of these steps much faster than the net flus as this would result in a proportionally large hydrolysis of ATP. Thus control of the steady state flus must be effected through the control of one or both of these two steps in cells in which glucose transport is rapid. In 1928, Barron and Harrop (5) reported that in the presence of methylene blue, the disappearance of glucose from mammalian blood was accelerated. This observation has been repeated and extended with purified human red cells (4, 6). One possible explanation for this effect is that methylene blue promotes the removal of glucose-6-P through the osidative path (4) so that its return to glucose by phosphatase reaction is diminished. Another hypothesis would be that the lowered glucose-6-P would cause diminished inhibition of hesokinase, an action consistent with the inhibitory effect of glucose-6-P on mammalian hexokinases (7-9). On the other hand, one could consider either direct activation of hesokinase or inactivation of phosphatase by methylene blue, a compound known to interact with a number of enzymes.
The present experiments show that the estent of increase in utilization seen in the presence of methylene blue is correlated with decreased glucose-6-P content and that there is no functional glucose 6-phosphatase in the erythrocyte, but that red cell hexokinase is inhibited by glucose-6-P to a degree consistent with the conclusion that it is the concentration of glucose-6-P
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