Effects of oxidant exposure on substrate utilization and high-energy phosphates in isolated rat hearts

Karen P. Burton, John G. Jones, Thuy H. Le, A. Dean Sherry, Craig R. Malloy

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The effects of a xanthine oxidase-mediated free radical-generating system containing purine and iron-loaded transferrin or solutions containing hydrogen peroxide and iron-loaded transferrin on substrate utilization and high-energy phosphates were evaluated by nuclear magnetic resonance (NMR) spectroscopy in isolated perfused rat hearts. Hearts were supplied with lactate, acetate, and glucose, and the contribution of each substrate to acetyl coenzyme A was measured in control hearts and in the presence of a free radical-generating system. Perfused hearts were monitored by 31P NMR, and tissue extracts were analyzed by 13C NMR. Free radicals decreased the phosphocreatine and β-ATP peak areas and reduced contractile function. Under control conditions, lactate, acetate, and endogenous sources were the major contributors of acetyl coenzyme A units, with only 5% originating from glucose. In the presence of a xanthine oxidase-mediated free radical- generating system, the glucose contribution increased to 54%, while contributions from acetate and endogenous sources were significantly reduced. Both 13C and 31P NMR analyses showed no significant accumulation of glycolytic sugar phosphates, suggesting little inhibition of glyceraldehyde- 3-phosphate dehydrogenase. The increased contribution of glucose to the tricarboxylic acid cycle relative to acetate and endogenous sources is consistent with activation of pyruvate dehydrogenase. In contrast, hearts exposed to a hydrogen peroxide-based free radical-generating system showed an increase in lactate utilization, a decrease in acetate utilization, and no change in glucose utilization compared with control hearts. Glycolytic sugar phosphates were found to accumulate, suggesting possible inhibition of glyceraldehyde-3-phosphate. Thus, different radicals or their metabolites may have varying effects on myocardial metabolism.

Original languageEnglish (US)
Pages (from-to)97-104
Number of pages8
JournalCirculation Research
Volume75
Issue number1
StatePublished - Jul 1994

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Oxidants
Free Radicals
Phosphates
Acetates
Glucose
Magnetic Resonance Spectroscopy
Sugar Phosphates
Lactic Acid
Acetyl Coenzyme A
Xanthine Oxidase
Transferrin
Hydrogen Peroxide
Iron
Glyceraldehyde 3-Phosphate
Glyceraldehyde-3-Phosphate Dehydrogenases
Tissue Extracts
Citric Acid Cycle
Phosphocreatine
Pyruvic Acid
Oxidoreductases

Keywords

  • C nuclear magnetic resonance
  • P nuclear magnetic resonance
  • free radicals
  • heart metabolism

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Effects of oxidant exposure on substrate utilization and high-energy phosphates in isolated rat hearts. / Burton, Karen P.; Jones, John G.; Le, Thuy H.; Sherry, A. Dean; Malloy, Craig R.

In: Circulation Research, Vol. 75, No. 1, 07.1994, p. 97-104.

Research output: Contribution to journalArticle

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