![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Molecular Pharmacology, Vol 2, 393-405, Copyright © 1966 by the American Society for Pharmacology and Experimental Therapeutics
1 Department of Pharmacology, Division of Basic Health Sciences,
Emory University, Atlanta, Georgic 30322
The intracellular distribution of hexokinase and the susceptibility of partly purified preparations of the enzyme to inhibition by glucose 6-phosphate was determined in the hearts of several species. The use of sucrose as a medium for fractionation of heart homogenates indicated that most of the enzyme was nonparticulate, but on differential centrifugation in isotonic KCl a large fraction of hexokinase activity was associated with mitochondria.
To test the hypothesis that glucose utilization is controlled through the inhibition of hexokinase by glucose-6-P, enzyme activity from heart mitochondria and soluble fraction was measured under conditions in which glucose-6-P was or was not allowed to accumulate. The apparent inhibitor constants for glucose-6-P ranged from 3 x 10-5 to 1.3 x 10-4 M in various preparations, and this inhibition was noncompetitive relative to ATP or glucose. However, aging of the enzyme prepared from dog heart resulted in a 3- to 10-fold increase in the apparent Ki, and an increase in the Km of ATP and the interaction between glucose-6-P and ATP became competitive. A change in the activity-pH relationship of hexokinase also occurred. Inorganic orthophosphate antagonized the inhibitory effect of glucose-6-P in concentrations comparable to physiological ones. This effect was lost on aging of dog heart mitochondria.
The data on the in vitro kinetics of heart hexokinase agree with observations of others on the control of glucose phosphorylation in perfused heart under conditions in which relatively large changes in glucose-6-P and inorganic phosphate concentrations occur such as after the administration of epinephrine and during anoxia, respectively. They are also in agreement with the fact that the administration of large doses of epinephrine to intact animals results in an increase in cardiac glucose 6-phosphate concentration and accumulation of intracellular glucose, presumably as a result of inhibition of hexokinase activity.
Submitted on April 18, 1966
This article has been cited by other articles:
|
|
 |
|
  C.-H. Kim, J. H. Youn, J.-Y. Park, S. K. Hong, K. S. Park, S. W. Park, K. I. Suh, and K.-U. Lee Effects of high-fat diet and exercise training on intracellular glucose metabolism in rats Am J Physiol Endocrinol Metab, June 1, 2000; 278(6): E977 - E984. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Doenst, Q. Han, G. W. Goodwin, P. H. Guthrie, and H. Taegtmeyer Insulin does not change the intracellular distribution of hexokinase in rat heart Am J Physiol Endocrinol Metab, October 1, 1998; 275(4): E558 - E567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Doenst and H. Taegtmeyer Profound Underestimation of Glucose Uptake by [18F]2-Deoxy-2-fluoroglucose in Reperfused Rat Heart Muscle Circulation, June 23, 1998; 97(24): 2454 - 2462. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
