Effects of different oxidative insults on intermediary metabolism in isolated perfused rat hearts

Free Radic Biol Med. 1996;20(4):515-23. doi: 10.1016/0891-5849(95)02088-8.


13C and 31P NMR were used to evaluate exogenous substrate utilization and endogenous phosphate metabolites in perfused rat hearts exposed to tert-butylhydroperoxide (tert-BOOH) and hydrogen peroxide (H2O2). Both reagents caused a reduction in developed pressure compared to controls and, in agreement with previous 31P NMR data, had different effects on intracellular high-energy phosphates and glycolysis. 13C Isotopomer analysis of tissue extracts showed that H2O2 and tert-BOOH also had significantly different effects on substrate utilization by the citric acid cycle. The contribution of exogenous lactate and glucose to acetyl-CoA was 43% in controls and increased to over 80% in the presence of either oxidant. With tert-BOOH, exogenous glucose and lactate were both significant contributors to acetyl-CoA (44 +/- 2 and 41 +/- 3%). However, with H2O2, exogenous lactate supplied a much higher fraction of acetyl-CoA (72 +/- 2%) than glucose (9 +/- 1%). Also, when [2-(13)C] glucose was supplied, accumulation of [2-(13)C] and [5-(13)C] fructose 1,6-bisphosphate was observed in the presence of H2O2, indicating inhibition of glyceraldehyde-3-phosphate dehydrogenase. These results indicate that despite this glycolytic inhibition, H2O2 increased the utilization of pyruvate precursors when lactate was present as an alternative carbohydrate substrate.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Citric Acid Cycle / physiology
  • Glutamic Acid / metabolism
  • Glutathione / metabolism
  • In Vitro Techniques
  • Magnetic Resonance Spectroscopy
  • Male
  • Myocardial Contraction / physiology
  • Myocardium / metabolism*
  • NADP / metabolism
  • Oxidation-Reduction
  • Perfusion
  • Phosphorus
  • Rats
  • Rats, Sprague-Dawley


  • Phosphorus
  • Glutamic Acid
  • NADP
  • Glutathione