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

John G. Jones, T. H. Le, C. J. Storey, A. Dean Sherry, Craig R. Malloy, Karen P. Burton

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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 [213C] glucose was supplied, accumulation of [2-13C] and 15-13C]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.

Original languageEnglish (US)
Pages (from-to)515-523
Number of pages9
JournalFree Radical Biology and Medicine
Volume20
Issue number4
DOIs
StatePublished - 1996

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Metabolism
Acetyl Coenzyme A
Rats
Lactic Acid
Glucose
Substrates
Phosphates
Nuclear magnetic resonance
tert-Butylhydroperoxide
Glyceraldehyde-3-Phosphate Dehydrogenases
Tissue Extracts
Citric Acid Cycle
Glycolysis
Metabolites
Pyruvic Acid
Oxidants
Hydrogen Peroxide
Carbohydrates
Pressure

Keywords

  • Citric acid cycle
  • Free radicals
  • Glycosis
  • High- energy phosphates
  • Isotopomer analysis
  • Oxidative stress

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Effects of different oxidative insults on intermediary metabolism in isolated perfused rat hearts. / Jones, John G.; Le, T. H.; Storey, C. J.; Sherry, A. Dean; Malloy, Craig R.; Burton, Karen P.

In: Free Radical Biology and Medicine, Vol. 20, No. 4, 1996, p. 515-523.

Research output: Contribution to journalArticle

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