Mechanisms involved in ketone body release by rat liver cells: influence of pH and bicarbonate

The aim of the present work is to study the intra- and extracellular concentration gradient of ketone bodies across the hepatic cell membrane, ketone bodies released by liver cells, and the effects of changes in acid-base status on these processes. Ketone bodies appeared to be released by liver cells against a concentration gradient both in vivo and in vitro (ratio intra- to extracellular, acetoacetate approximately 0.5, 3-hydroxybutyrate approximately 0.8). In vitro, a decrease in external pH and bicarbonate gradient was associated with a reduction of ketone body gradients and efflux rates. Analysis of the distribution ratio of ketone bodies as a function of delta pH across the cell membrane indicates that additional factors must be invoked to account for the observed distribution ratios. These data along with measurements of ketone body efflux are consistent with the existence of a system promoting the efflux of ketone bodies from liver cells, which is trans-stimulated by external bicarbonate. In vivo, ketogenesis was also inhibited by acidosis, and slightly enhanced by bicarbonate infusion, although this was not solely due to effects on transfer across the cell membrane. The study indicates that the hepatic release of ketone bodies might be auto-limited by ketoacidosis.