Transport of N-acetylglutamate in rat-liver mitochondria.

Abstract

The permeability properties of the rat-liver mitochondrial membrane for N-acetylglutamate, the activator of carbamoyl-phosphate synthetase (ammonia), were studied. 1. Transport of N-acetylglutamate into the mitochondria was only observed in partially or fully de-energized mitochondria and when the extramitochondrial concentration was unphysiologically high (in the mM range). However, even under these conditions the intramitochondrial concentration of N-acetylglutamate was much lower than that outside. 2. Mitochondrial N-acetylglutamate efflux only occurs when the mitochondria are in an energized state. At 25 degrees C, at an intramitochondrial N-acetylglutamate concentration of 0.7-1.0 nmol/mg protein, efflux proceeds at a rate of about 0.05 nmol X min-1 X mg protein-1. This is 10-fold lower than the maximal rate of N-acetylglutamate synthesis in the mitochondria. 3. Homologous exchange between intramitochondrial N-[14C]acetylglutamate and extramitochondrial unlabelled N-acetylglutamate could not be demonstrated. 4. It is concluded that transport of N-acetylglutamate in vivo is effectively unidirectional, out of the mitochondria. This behaviour is in accordance with the physiological requirement for efflux of N-acetylglutamate from the mitochondria in order to be degraded in the cytosol.