TY - JOUR
T1 - Respiratory control and substrate effects in the working rat heart
AU - Jeffrey, F. M H
AU - Malloy, C. R.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1992
Y1 - 1992
N2 - 31P n.m.r. spectroscopy was used to measure the concentration of phosphates commonly proposed to control oxidative phosphorylation. The effect of loading conditions, β-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][P(i)]. 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 can not 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.
AB - 31P n.m.r. spectroscopy was used to measure the concentration of phosphates commonly proposed to control oxidative phosphorylation. The effect of loading conditions, β-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][P(i)]. 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 can not 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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U2 - 10.1042/bj2870117
DO - 10.1042/bj2870117
M3 - Article
C2 - 1417763
AN - SCOPUS:0026802941
SN - 0264-6021
VL - 287
SP - 117
EP - 123
JO - Biochemical Journal
JF - Biochemical Journal
IS - 1
ER -