Respiratory control and substrate effects in the working rat heart

31P n.m.r. spectroscopy was used to measure the concentration of phosphates commonly proposed to control oxidative phosphorylation. The effect of loading conditions, beta-adrenergic stimulation and different substrates (acetate, pyruvate or glucose) was examined under steady-state conditions in the...

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Veröffentlicht in:Biochemical journal 1992-10, Vol.287 (1), p.117-123
Hauptverfasser: JEFFREY, F. M. H, MALLOY, C. R
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description 31P n.m.r. spectroscopy was used to measure the concentration of phosphates commonly proposed to control oxidative phosphorylation. The effect of loading conditions, beta-adrenergic stimulation and different substrates (acetate, pyruvate or glucose) was examined under steady-state conditions in the isolated working rat heart. Oxygen consumption and haemodynamic variables were monitored continuously. In response to a 2-fold increase in afterload, there were no significant changes in [ADP], [ATP]/[ADP], or [ATP]/[ADP][Pi]. In the presence of isoprenaline, these variables also tended not to change from afterload. However, isoprenaline, at identical perfusion pressures, consistently decreased the phosphorylation potential and [ATP]/[ADP], but had little effect on [ADP]. Substrates altered the phosphate metabolites in a manner independent of oxygen consumption, and had only minor effects on the relationship between phosphates and work, in contrast with other studies. Thus, metabolites of ATP synthesis are not normally involved in respiratory control. The 31P n.m.r. spectrum can vary greatly, but does not predict oxygen consumption in this preparation. Substrates have no effect on the mechanism of respiratory control. Thus the normal control of respiration in the heart at steady state cannot occur at the level of its substrates. Rather, there must be concerted regulation of the numerous pathways, involving allostery and covalent modification. The attention of future research should be shifted away from the metabolites of ATP and towards identifying the effectors of such regulation.
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Substrates altered the phosphate metabolites in a manner independent of oxygen consumption, and had only minor effects on the relationship between phosphates and work, in contrast with other studies. Thus, metabolites of ATP synthesis are not normally involved in respiratory control. The 31P n.m.r. spectrum can vary greatly, but does not predict oxygen consumption in this preparation. Substrates have no effect on the mechanism of respiratory control. Thus the normal control of respiration in the heart at steady state cannot occur at the level of its substrates. Rather, there must be concerted regulation of the numerous pathways, involving allostery and covalent modification. 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M. H</creatorcontrib><creatorcontrib>MALLOY, C. R</creatorcontrib><title>Respiratory control and substrate effects in the working rat heart</title><title>Biochemical journal</title><addtitle>Biochem J</addtitle><description>31P n.m.r. spectroscopy was used to measure the concentration of phosphates commonly proposed to control oxidative phosphorylation. The effect of loading conditions, beta-adrenergic stimulation and different substrates (acetate, pyruvate or glucose) was examined under steady-state conditions in the isolated working rat heart. Oxygen consumption and haemodynamic variables were monitored continuously. In response to a 2-fold increase in afterload, there were no significant changes in [ADP], [ATP]/[ADP], or [ATP]/[ADP][Pi]. In the presence of isoprenaline, these variables also tended not to change from afterload. 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Psychology</topic><topic>Glucose - metabolism</topic><topic>Heart</topic><topic>Hemodynamics</topic><topic>Hydrogen-Ion Concentration</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>mechanisms</topic><topic>Myocardium - metabolism</topic><topic>Oxygen Consumption</topic><topic>Phosphates - metabolism</topic><topic>Pyruvates - metabolism</topic><topic>Rats</topic><topic>regulation</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>JEFFREY, F. M. H</creatorcontrib><creatorcontrib>MALLOY, C. 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R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Respiratory control and substrate effects in the working rat heart</atitle><jtitle>Biochemical journal</jtitle><addtitle>Biochem J</addtitle><date>1992-10-01</date><risdate>1992</risdate><volume>287</volume><issue>1</issue><spage>117</spage><epage>123</epage><pages>117-123</pages><issn>0264-6021</issn><eissn>1470-8728</eissn><abstract>31P n.m.r. spectroscopy was used to measure the concentration of phosphates commonly proposed to control oxidative phosphorylation. The effect of loading conditions, beta-adrenergic stimulation and different substrates (acetate, pyruvate or glucose) was examined under steady-state conditions in the isolated working rat heart. Oxygen consumption and haemodynamic variables were monitored continuously. In response to a 2-fold increase in afterload, there were no significant changes in [ADP], [ATP]/[ADP], or [ATP]/[ADP][Pi]. In the presence of isoprenaline, these variables also tended not to change from afterload. However, isoprenaline, at identical perfusion pressures, consistently decreased the phosphorylation potential and [ATP]/[ADP], but had little effect on [ADP]. Substrates altered the phosphate metabolites in a manner independent of oxygen consumption, and had only minor effects on the relationship between phosphates and work, in contrast with other studies. Thus, metabolites of ATP synthesis are not normally involved in respiratory control. The 31P n.m.r. spectrum can vary greatly, but does not predict oxygen consumption in this preparation. Substrates have no effect on the mechanism of respiratory control. Thus the normal control of respiration in the heart at steady state cannot occur at the level of its substrates. Rather, there must be concerted regulation of the numerous pathways, involving allostery and covalent modification. 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subjects Acetates - metabolism
Adenine Nucleotides - metabolism
Animals
Biological and medical sciences
cardiac muscle
electron transport
Energy Metabolism
Fundamental and applied biological sciences. Psychology
Glucose - metabolism
Heart
Hemodynamics
Hydrogen-Ion Concentration
Magnetic Resonance Spectroscopy
mechanisms
Myocardium - metabolism
Oxygen Consumption
Phosphates - metabolism
Pyruvates - metabolism
Rats
regulation
Vertebrates: cardiovascular system
title Respiratory control and substrate effects in the working rat heart
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