Journal of Applied Physiology, Vol 63, Issue 5 1776-1780, Copyright © 1987 by American Physiological Society
Dependence of hepatic gluconeogenesis on PO2: inhibitory effects of halothane
F. J. Romero, F. V. Pallardo, R. Bolinches, J. Roma, G. T. Saez, T. Noll and H. de Groot
Departamentos de Fisiologia and Bioquimica, Facultad de Medicina, Universitat de Valencia, Spain.
The dependence of gluconeogenesis and O2 uptake on PO2 in isolated rat
hepatocytes is presented. Maintenance of steady-state PO2 was achieved with
an oxystat system (Biochem. J. 236: 765-769, 1986). O2 uptake showed a
half-maximal (K0.5) value of 0.5 Torr PO2, whereas the glucose synthesis
rate was half-maximal at 1.2 Torr PO2. Halothane at concentrations greater
than 1 mM exerted a parallel inhibition of O2 uptake and glucose synthesis
at all PO2 levels studied. In contrast, at halothane concentrations less
than 1 mM, inhibition of glucose synthesis occurred only at less than 20
Torr PO2. At these low concentrations, halothane was without significant
effects on cellular O2 uptake. In isolated mitochondria, inhibition of O2
uptake was already half-maximal at a halothane concentration of 0.5 mM. In
this subcellular system the inhibitory effect of halothane was independent
of PO2. These results demonstrate that the critical PO2 at which cellular
O2 utilization begins to decrease and the PO2 at which glucose synthesis
begins to decrease are comparable; both PO2 levels are approximately 5
Torr. The metabolic zonation of the liver lobule is discussed in view of
the results presented.
