The effects of cyclopropane carboxylate on hepatic pyruvate metabolism

Abstract

The effects of cyclopropane carboxylate on gluconeogenesis and pyruvate decarboxylation from [1- 14C]-labeled pyruvate and lactate were investigated in perfused livers from fasted rats. With high concentrations of pyruvate (⩾0.5 m m) in the perfusion medium, infusion of cyclopropane carboxylate inhibited pyruvate decarboxylation and gluconeogenesis by 30 and 40%.respectively. With low, more physiological concentrations of pyruvate (50 μ m) or with lactate (1 m m), cyclopropane carboxylate, at a concentration which elicits maximal inhibition of pyruvate decarboxylation from pyruvate (⩾0.5 m m), did not affect either pyruvate decarboxylation or gluconeogenesis. Evidence is presented for the rapid formation of the coenzyme-A ester of cyclopropane carboxylate in perfused livers. Infusion of l-(−)carnitine (20 m m) prevented the inhibitory effects of cyclopropane carboxylate on pyruvate decarboxylation and gluconeogenesis from pyruvate (⩾0.5 m m. Interestingly, no decrease in the tissue level of cyclopropanecarboxyl-CoA occurs under these conditions. The present study suggests that cyclopropane carboxylate, through a presently ill-defined mediator, inhibits pyruvate decarboxylation and gluconeogenesis by interfering with the pyruvate → oxalacetate → phosphoenolpyruvate → pyruvate cycle when pyruvate (⩾0.5 m m) supports gluconeogenesis.