Regulation of urea synthesis. The effect of ammonia on the N-acetylglutamate content of isolated rat liver cells.

(1) Incubation of isolated rat liver cells in the presence of lactate and ammonia increases the AcGlu content. The increase is very fast in the first minutes and a steady-state concentration is reached in approx. 10 min after the addition of ammonia. (2) The amount of increase depends on the diet rats were fed before isolation of liver cells. AcGlu is increased 4-fold in hepatocytes from rats fed a carbohydrate-rich diet. If ornithine is simultaneously present with ammonia a further increase is found. (3) Urea synthesis in hepatocytes from rats fed a carbohydrate-rich diet has a marked lag period. The reason for this lag phase is the low initial AcGlu concentration. (4) Increase in AcGlu is closely associated with increase in mitochondrial glutamate content. Thus, it is concluded that the glutamate concentration is the mediator of the ammonia effect.