The Relationship between Intramitochondrial N‐Acetylglutamate and Activity of Carbamoyl‐Phosphate Synthetase (Ammonia)

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Abstract
1 The relationship between urea synthesis, intracellular N-acetylglutamate and the capacity of rat-liver mitochondria to synthesize citrulline was investigated. 2 Treatment of rats with glucagon prior to killing results not only in an increased intra-mitochondrial ATP concentration and an increased capacity of the mitochondria to synthesize citrulline, but also in an increased concentration of intramitochondrial N-acetylglutamate. 3 Comparison of the rate of citrulline synthesis in mitochondria from glucagon-treated and from control rats, incubated under different conditions, shows that the increased N-acetylglutamate concentration after glucagon treatment is at least in part responsible for the observed increased capacity of the mitochondria to synthesize citrulline. 4 Ureogenic flux in isolated hepatocytes under different incubation conditions correlated with the intracellular concentration of N-acetylglutamate and with the capacity of the mitochondria to synthesize citrulline. 5 When isolated hepatocytes were incubated with NH3, ornithine, lactate and oleate, intracellular N-acetylglutamate increased about eightfold in the first 10 min; during this period the rate of urea synthesis increased considerably. 6 It is concluded that the concentration of intramitochondrial N-acetylglutamate plays an important role in the short-term control of flux through the urea cycle under different nutritional and hormonal conditions.