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. 1996 Mar 15;97(6):1409–1416. doi: 10.1172/JCI118561

Preferential oxidation of glycogen in isolated working rat heart.

G W Goodwin 1, F Ahmad 1, H Taegtmeyer 1
PMCID: PMC507199  PMID: 8617872

Abstract

We tested the hypothesis that glycogen is preferentially oxidized in isolated working rat heart. This was accomplished by measuring the proportion of glycolytic flux (oxidation plus lactate production) specifically from glycogen which is metabolized to lactate, and comparing it to the same proportion determined concurrently from exogenous glucose during stimulation with epinephrine. After prelabeling of glycogen with either 14C or 3H, a dual isotope technique was used to simultaneously trace the disposition of glycogen and exogenous glucose between oxidative and non-oxidative pathways. Immediately after the addition of epinephrine (1 microM), 40-50% of flux from glucose was directed towards lactate. Glycogen, however, did not contribute to lactate, being almost entirely oxidized. Further, glycogen utilization responded promptly to the abrupt increase in contractile performance with epinephrine, during the lag in stimulation of utilization of exogenous glucose, suggesting that glycogen serves as substrate reservoir to buffer rapid increases in demand. Preferential oxidation of glycogen may serve to ensure efficient generation of ATP from a limited supply of endogenous substrate, or as a mechanism to limit lactate accumulation during rapid glycogenolysis.

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Selected References

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  1. Bontemps F., Hue L., Hers H. G. Phosphorylation of glucose in isolated rat hepatocytes. Sigmoidal kinetics explained by the activity of glucokinase alone. Biochem J. 1978 Aug 15;174(2):603–611. doi: 10.1042/bj1740603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brainard J. R., Hutson J. Y., Hoekenga D. E., Lenhoff R. Ordered synthesis and mobilization of glycogen in the perfused heart. Biochemistry. 1989 Dec 12;28(25):9766–9772. doi: 10.1021/bi00451a033. [DOI] [PubMed] [Google Scholar]
  3. Burant C. F., Sivitz W. I., Fukumoto H., Kayano T., Nagamatsu S., Seino S., Pessin J. E., Bell G. I. Mammalian glucose transporters: structure and molecular regulation. Recent Prog Horm Res. 1991;47:349–388. doi: 10.1016/b978-0-12-571147-0.50015-9. [DOI] [PubMed] [Google Scholar]
  4. Butler P., Bell P., Rizza R. Choice and use of tracers. Horm Metab Res Suppl. 1990;24:20–25. [PubMed] [Google Scholar]
  5. Clark M. G., Bloxham D. P., Holland P. C., Lardy H. A. Estimation of the fructose 1,6-diphosphatase-phosphofructokinase substrate cycle and its relationship to gluconeogenesis in rat liver in vivo. J Biol Chem. 1974 Jan 10;249(1):279–290. [PubMed] [Google Scholar]
  6. Cross H. R., Clarke K., Opie L. H., Radda G. K. Is lactate-induced myocardial ischaemic injury mediated by decreased pH or increased intracellular lactate? J Mol Cell Cardiol. 1995 Jul;27(7):1369–1381. doi: 10.1006/jmcc.1995.0130. [DOI] [PubMed] [Google Scholar]
  7. De Tata V., Bergamini C., Gori Z., Locci-Cubeddu T., Bergamini E. Transmural gradient of glycogen metabolism in the normal rat left ventricle. Pflugers Arch. 1983 Jan;396(1):60–65. doi: 10.1007/BF00584699. [DOI] [PubMed] [Google Scholar]
  8. Devos P., Hers H. G. A molecular order in the synthesis and degradation of glycogen in the liver. Eur J Biochem. 1979 Aug 15;99(1):161–167. doi: 10.1111/j.1432-1033.1979.tb13242.x. [DOI] [PubMed] [Google Scholar]
  9. Goodwin G. W., Arteaga J. R., Taegtmeyer H. Glycogen turnover in the isolated working rat heart. J Biol Chem. 1995 Apr 21;270(16):9234–9240. doi: 10.1074/jbc.270.16.9234. [DOI] [PubMed] [Google Scholar]
  10. Goodwin G. W., Taegtmeyer H. Metabolic recovery of isolated working rat heart after brief global ischemia. Am J Physiol. 1994 Aug;267(2 Pt 2):H462–H470. doi: 10.1152/ajpheart.1994.267.2.H462. [DOI] [PubMed] [Google Scholar]
  11. Hardin C. D., Kushmerick M. J. Simultaneous and separable flux of pathways for glucose and glycogen utilization studied by 13C-NMR. J Mol Cell Cardiol. 1994 Sep;26(9):1197–1210. doi: 10.1006/jmcc.1994.1138. [DOI] [PubMed] [Google Scholar]
  12. Hue L. The role of futile cycles in the regulation of carbohydrate metabolism in the liver. Adv Enzymol Relat Areas Mol Biol. 1981;52:247–331. doi: 10.1002/9780470122976.ch4. [DOI] [PubMed] [Google Scholar]
  13. KIRK E. S., HONIG C. R. NONUNIFORM DISTRIBUTION OF BLOOD FLOW AND GRADIENTS OF OXYGEN TENSION WITHIN THE HEART. Am J Physiol. 1964 Sep;207:661–668. doi: 10.1152/ajplegacy.1964.207.3.661. [DOI] [PubMed] [Google Scholar]
  14. Kannengiesser G. J., Opie L. H., van der Werff T. J. Impaired cardiac work and oxygen uptake after reperfusion of regionally ischaemic myocardium. J Mol Cell Cardiol. 1979 Feb;11(2):197–207. doi: 10.1016/0022-2828(79)90464-4. [DOI] [PubMed] [Google Scholar]
  15. Kashiwaya Y., Sato K., Tsuchiya N., Thomas S., Fell D. A., Veech R. L., Passonneau J. V. Control of glucose utilization in working perfused rat heart. J Biol Chem. 1994 Oct 14;269(41):25502–25514. [PubMed] [Google Scholar]
  16. Lundsgaard-hansen P., Meyer C., Riedwyl H. Transmural gradients of glycolytic enzyme activities in left ventricular myocardium. I. The normal state. Pflugers Arch Gesamte Physiol Menschen Tiere. 1967;297(2):89–106. doi: 10.1007/BF00363632. [DOI] [PubMed] [Google Scholar]
  17. Lynch R. M., Paul R. J. Compartmentation of glycolytic and glycogenolytic metabolism in vascular smooth muscle. Science. 1983 Dec 23;222(4630):1344–1346. doi: 10.1126/science.6658455. [DOI] [PubMed] [Google Scholar]
  18. Neely J. R., Rovetto M. J., Whitmer J. T., Morgan H. E. Effects of ischemia on function and metabolism of the isolated working rat heart. Am J Physiol. 1973 Sep;225(3):651–658. doi: 10.1152/ajplegacy.1973.225.3.651. [DOI] [PubMed] [Google Scholar]
  19. Srere P. A. Complexes of sequential metabolic enzymes. Annu Rev Biochem. 1987;56:89–124. doi: 10.1146/annurev.bi.56.070187.000513. [DOI] [PubMed] [Google Scholar]
  20. Taegtmeyer H., Hems R., Krebs H. A. Utilization of energy-providing substrates in the isolated working rat heart. Biochem J. 1980 Mar 15;186(3):701–711. doi: 10.1042/bj1860701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. WALAAS O., WALAAS E. Effect of epinephrine on rat diaphragm. J Biol Chem. 1950 Dec;187(2):769–776. [PubMed] [Google Scholar]
  22. Weiss J. N., Lamp S. T. Glycolysis preferentially inhibits ATP-sensitive K+ channels in isolated guinea pig cardiac myocytes. Science. 1987 Oct 2;238(4823):67–69. doi: 10.1126/science.2443972. [DOI] [PubMed] [Google Scholar]
  23. Xu K. Y., Zweier J. L., Becker L. C. Functional coupling between glycolysis and sarcoplasmic reticulum Ca2+ transport. Circ Res. 1995 Jul;77(1):88–97. doi: 10.1161/01.res.77.1.88. [DOI] [PubMed] [Google Scholar]

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