The role of amino acids and their transport systems in the regulation of ureogenesis in the primary culture of adult rat hepatocytes.

The biosynthesis of urea, the metabolism of ammonia and the transport of amino acids were studied using the primary culture of hepatocytes from adult rats. The urea synthesis and ammonia detoxication were affected by the amino acids of urea cycle intermediates, such as ornithine, arginine and aspartate. When the hepatocytes were incubated in the medium containing 1 mM ammonium chloride, the transport activity of system-A, which was determined by the uptake of specific substrate methyl-2-amino isobutyric acid (MeAIB), did not change compared with the control level. However, the transport activity of ornithine was increased to a maximum after 4 hr of incubation with ammonia, and then decreased gradually to twice the control level. The activity of ornithine transcarbamylase (OTC) increased to twice the control. These results indicated that the amino acids of urea cycle intermediates, especially ornithine, can be the important regulators of ureogenesis.