| Regulation of glycolytic flux in ischemic preconditioning. A study employing metabolic control analysis. | |
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MedLine Citation:
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PMID: 12006584 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Exact adjustment of the Embden-Meyerhof pathway (EMP) is an important issue in ischemic preconditioning (IP) because an attenuated ischemic lactate accumulation contributes to myocardial protection. However, precise mechanisms of glycolytic flux and its regulation in IP remain to be elucidated. In open chest pigs, IP was achieved by two cycles of 10-min coronary artery occlusion and 30-min reperfusion prior to a 45-min index ischemia and 120-min reperfusion. Myocardial contents in glycolytic intermediates were assessed by high performance liquid chromatographic analysis of serial myocardial biopsies under control conditions and IP. Detailed time courses of metabolite contents allow an in-depth description of EMP regulation during index ischemia using metabolic control analysis. IP reduced myocardial infarct size (control, 90.0 +/- 3.1 versus 5.05 +/- 2.1%; p < 0.001) and attenuated myocardial lactate accumulation (end-ischemic contents, 31.9 +/- 4.47 versus 10.3 +/- 1.26 micromol/wet weight, p < 0.0001), whereby a decrease in anaerobic glycolytic flux by at least 70% could constantly be observed throughout index ischemia. By calculation of flux:metabolite co-responses, the mechanisms of glycolytic regulation were investigated. The continuous deceleration of EMP flux in control myocadium could neither be explained on the basis of substrate availability nor be attributed to regulatory "key enzymes," as multisite regulation was employed for flux adjustment. In myocardium subjected to IP, an even pronounced deceleration of EMP flux during index ischemia was observed. Again, the adjustment of EMP flux was because of multisite modulation without any evidence for flux limitation by substrate availability or a key enzyme. However, IP changed the regulatory properties of most EMP enzymes, and some of these patterns could not be explained on the basis of substrate kinetics. Instead, other regulatory mechanisms, which have previously not yet been described for EMP enzymes, must be considered. These altered biochemical properties of the EMP enzymes have not yet been described. |
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Authors:
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Achim M Vogt; Mark Poolman; Cordula Ackermann; Murat Yildiz; Wolfgang Schoels; David A Fell; Wolfgang Kubler |
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Publication Detail:
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Type: Journal Article Date: 2002-05-02 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 277 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2002 Jul |
Date Detail:
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Created Date: 2002-07-01 Completed Date: 2002-08-27 Revised Date: 2003-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 24411-9 Citation Subset: IM |
Affiliation:
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Medizinische Universitätsklinik (Ludolf-Krehl-Klinik), Abteilung Innere Medizin III (Schwerpunkt Kardiologie, Angiologie und Pulmologie), Bergheimer Strasse 58, D-69115 Heidelberg, Germany. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Anaerobiosis Animals Chromatography, High Pressure Liquid Coronary Vessels / physiology Glycogen Phosphorylase / metabolism Glycogen Synthase / metabolism Glycolysis / physiology Homeostasis Ischemic Preconditioning, Myocardial* Lactates / metabolism Myocardium / metabolism* Reperfusion Swine |
| Chemical | |
Reg. No./Substance:
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0/Lactates; EC 2.4.1.-/Glycogen Phosphorylase; EC 2.4.1.11/Glycogen Synthase |
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