AJP - Endocrinology and Metabolism, Vol 261, Issue 2 E221-E226, Copyright © 1991 by American Physiological Society
Effects of extracellular pH, CO2, and HCO3- on ketogenesis in perfused rat liver
G. Y. Wu, A. Gunasekara, H. Brunengraber and E. B. Marliss
McGill Nutrition and Food Science Center, Royal Victoria Hospital, Montreal, Quebec, Canada.
Effects of extracellular pH, CO2, and HCO3- on ketone body production from
octanoate were studied in perfused livers from fasted rats. pH was adjusted
to 7.1-7.5 by varying perfusate [HCO3-] and [CO2], where brackets denote
concentration. At constant 25 mM [HCO3-], total production of
beta-hydroxybutyrate (beta-OHB) + acetoacetate (AcAc) was constant from pH
7.1 to 7.5. However, the [beta-OHB]/[AcAc] ratio decreased from 1.60 to
1.00 when pH decreased from 7.3 to 7.1; there was no change at pH 7.4. At
constant [CO2], decreasing pH from 7.4 to 7.1 did not alter either total
ketogenesis or the [beta-OHB]/[AcAc] ratio. This suggests that high [CO2]
rather than low pH was responsible for the alteration in the redox ratio.
At constant pH of 7.4, variations in [HCO3-] between 15 and 25 mM did not
influence total ketogenesis or the [beta-OHB]/[AcAc] ratio. However,
increasing [HCO3-] from 25 to 35 mM decreased the [beta-OHB]/[AcAc] ratio
from 1.76 to approximately 1, again without affecting total ketogenesis. At
constant 1.75 mM [CO2], increasing [HCO3-] from 25 to 35 mM also reduced
the [beta-OHB]/[AcAc] ratio from 1.63 to approximately 1, suggesting that
the effect of high [HCO3-] on this redox ratio can be ascribed to HCO3-
itself. It is concluded that high [CO2] or [HCO3-] decreases the
mitochondrial [NADH]/[NAD+] ratio in hepatocytes, resulting in a decreased
[beta-OHB]/[AcAc] ratio.
