Respiratory control and substrate effects in the working rat heart

F. M H Jeffrey, C. R. Malloy

Research output: Contribution to journalArticle

33 Citations (Scopus)

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, 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.

Original languageEnglish (US)
Pages (from-to)117-123
Number of pages7
JournalBiochemical Journal
Volume287
Issue number1
StatePublished - 1992

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Adenosine Diphosphate
Rats
Adenosine Triphosphate
Metabolites
Oxygen Consumption
Substrates
Phosphates
Oxygen
Isoproterenol
Phosphorylation
Oxidative Phosphorylation
Hemodynamics
Pyruvic Acid
Adrenergic Agents
Spectrum Analysis
Respiration
Acetates
Perfusion
Spectroscopy
Pressure

ASJC Scopus subject areas

  • Biochemistry

Cite this

Respiratory control and substrate effects in the working rat heart. / Jeffrey, F. M H; Malloy, C. R.

In: Biochemical Journal, Vol. 287, No. 1, 1992, p. 117-123.

Research output: Contribution to journalArticle

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