Carnitine import to isolated hepatocytes and synthesis are accelerated in pivalate-treated rats

To investigate the effect of pivalate on carnitine import and carnitine syn thesis in the liver, we measured carnitine uptake in isolated rat hepatocyt es with L-[C-14] carnitine and concentrations of free carnitine, gamma-buty robetaine and acylcamitines using tandem mass spectrometry, Hepatocytes fro m rats treated with 20 mmol/L of pivalate for 4 wk had greater L-[C-14] car nitine uptake than those of unsupplemented rats after 5, 10, 30 and 90 min. Addition of 1 mmol/L of pivalate or 1 mmol/L of pivaloylcarnitine to contr ol cell suspensions did not affect L-[C-14] carnitine uptake. The K-m value s for L-[C-14] carnitine uptake for pivalate-treated rats were significantl y lower than control (2.9 +/- 0.7 mmol/L for pivalate-treated rats, 6.2 +/- 1.1 mmol/L for controls). The concentration of free carnitine was not redu ced in the liver of pivalate-treated rats, whereas the concentrations of ac etylcarnitine and gamma-butyrobetaine were significantly lower than control s. In the heart and muscle the concentration of free carnitine was signific antly lower and that of gamma-butyrobetaine was higher than controls, These results suggest that carnitine transport from plasma into the liver and sy nthesis in the liver are accelerated in rats with secondary carnitine defic iency induced by the administration of pivalate.