© 2002 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Elevated hexokinase increases cardiac glycolysis in transgenic mice
Department of Pharmacology, University of North Dakota, Grand Forks, ND 58202, USA
* Corresponding author. Department of Pediatrics, University of Louisville, 570 South Preston Street, Suite 304, Louisville, KY 40202, USA. Tel.: +1-502-852-2655; fax: +1-502-852-5634 paul.epstein{at}louisville.edu
Objective: Cardiac glucose metabolism is critical to normal and pathological function. The significance of the first committed metabolic step, glucose phosphorylation, has not been established. In this study a new transgenic model was developed in order to investigate the importance of this enzymatic step in cardiac glycolysis. Methods: Transgenic mice were produced that overexpress yeast hexokinase B under the control of a cardiac specific promoter. Yeast hexokinase B is a high affinity enzyme that is not inhibited by glucose-6-phosphate. Hexokinase enzyme activity was measured by a modified radiometric procedure. Cardiac glucose metabolism and contractility were measured in the Langendorff mode. Cardiac glycogen content and glucose-6-phosphate independent glycogen synthase activity were also determined. Results: In transgenic hearts hexokinase activity was significantly elevated and increased glucose metabolism, particularly in the presence of insulin and during cardiac reperfusion. However during ischemic perfusion the effect of the transgene on glycolysis was minimal. Under all conditions tested there was no effect of hexokinase on contractility. Glycogen content of transgenic hearts was elevated 2-fold and glucose-6-phosphate independent glycogen synthase was also increased. Conclusion: These results demonstrate that glucose phosphorylation is a key step in determining cardiac glucose metabolism under oxidative conditions.
KEYWORDS Energy metabolism; Enzyme (kinetics); Glycolysis
1 The first two authors contributed equally to this work.
2 Present address: Division of Molecular Cardiovascular Biology, Children's Hospital Medical Center, Cincinnati, OH 45229-3097, USA.
3 Present address: Department of Pediatrics, University of Louisville, Louisville, KY 40202, USA.
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