Document Detail

Effects of oxidant exposure on substrate utilization and high-energy phosphates in isolated rat hearts.
MedLine Citation:
PMID:  7912169     Owner:  NLM     Status:  MEDLINE    
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 beta-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.
K P Burton; J G Jones; T H Le; A D Sherry; C R Malloy
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation research     Volume:  75     ISSN:  0009-7330     ISO Abbreviation:  Circ. Res.     Publication Date:  1994 Jul 
Date Detail:
Created Date:  1994-07-26     Completed Date:  1994-07-26     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  97-104     Citation Subset:  IM    
Department of Radiology, University of Texas Southwestern Medical Center, Dallas 75235-9071.
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MeSH Terms
Acetates / metabolism
Carbon Isotopes
Energy Metabolism / drug effects*
Glutamates / metabolism
Glutamic Acid
Lactates / metabolism
Lactic Acid
Magnetic Resonance Spectroscopy
Myocardium / metabolism*
Oxidants / pharmacology*
Phosphates / metabolism*
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism
Grant Support
Reg. No./Substance:
0/Acetates; 0/Carbon Isotopes; 0/Glutamates; 0/Lactates; 0/Oxidants; 0/Phosphates; 0/Reactive Oxygen Species; 50-21-5/Lactic Acid; 56-86-0/Glutamic Acid; 7723-14-0/Phosphorus

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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