Document Detail


Reverse flux through cardiac NADP(+)-isocitrate dehydrogenase under normoxia and ischemia.
MedLine Citation:
PMID:  12234803     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Little is known about the role of mitochondrial NADP(+)-isocitrate dehydrogenase (NADP(+)-ICDH) in the heart, where this enzyme shows its highest expression and activity. We tested the hypothesis that in the heart, NADP(+)-ICDH operates in the reverse direction of the citric acid cycle (CAC) and thereby may contribute to the fine regulation of CAC activity (Sazanov and Jackson, FEBS Lett 344: 109-116, 1994). We documented a reverse flux through this enzyme in rat hearts perfused with the medium-chain fatty acid octanoate using [U-(13)C(5)]glutamate and mass isotopomer analysis of tissue citrate (Comte et al., J Biol Chem 272: 26117-26124, 1997). In this study, we assessed the significance of our previous finding by perfusing hearts with long-chain fatty acids and tested the effects of changes in O(2) supply. We showed that under all of these conditions citrate was enriched in an isotopomer containing five (13)C atoms. This isotopomer can only be explained by substrate flux through reversal of the NADP(+)-ICDH reaction, which is evaluated at 3-7% of flux through citrate synthase. Small variations in reversal fluxes induced by low-flow ischemia that mimicked hibernation occurred despite major changes in contractile function and O(2) consumption of the heart as well as citrate and succinate release rates and tissue levels. Our data show a reverse flux through NADP(+)-ICDH and support its hypothesized role in the fine regulation of CAC activity in the normoxic and O(2)-deprived heart.
Authors:
Blandine Comte; Geneviève Vincent; Bertrand Bouchard; Mohamed Benderdour; Christine Des Rosiers
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  283     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-09-17     Completed Date:  2002-10-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1505-14     Citation Subset:  IM    
Affiliation:
Department of Nutrition, University of Montreal, Quebec H3C 3J7, Canada.
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MeSH Terms
Descriptor/Qualifier:
Aconitate Hydratase / metabolism
Animals
Carbon Isotopes / diagnostic use
Citrate (si)-Synthase / metabolism
Citric Acid / metabolism
Citric Acid Cycle / physiology
Isocitrate Dehydrogenase / metabolism*
Male
Myocardial Ischemia / metabolism*
Myocardium / enzymology*
NAD / metabolism
NADP / metabolism*
Oxygen / pharmacology
Perfusion
Rats
Rats, Sprague-Dawley
Chemical
Reg. No./Substance:
0/Carbon Isotopes; 53-59-8/NADP; 53-84-9/NAD; 77-92-9/Citric Acid; 7782-44-7/Oxygen; EC 1.1.1.41/Isocitrate Dehydrogenase; EC 2.3.3.1/Citrate (si)-Synthase; EC 4.2.1.3/Aconitate Hydratase

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


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