Stimulation of alanine metabolism in rat liver by ammonia

The effect of ammonia on the alanine metabolism was investigated in perfused rat liver. Gluconeogenesis was found to be stimulated by physiological concentrations of ammonia, while being inhibited at higher concentrations (5-10 mM). The stimulating effect of 0.5 mM ammonia was studied in greater detail. In addition to glucose formation seen enhanced five times, increased rates were observed for ureogenesis as well as the formation of lactate and pyruvate, demonstrating also activation of the total alanine turnover. Furthermore, the mitochondrial and cytosolic NAD systems were increasingly oxidized as reflected by the beta-hydroxybutyrate/acetoacetate and lactate/pyruvate ratios. The shift of the beta-hydroxybutyrate/acetoacetate ratio was correlated to the ATP demand by gluconeogenesis and ureogenesis. The elevated concentration of pyruvate was found to have caused stimulation of gluconeogenesis since there existed a Michaelis-Menten type relation between pyruvate concentration and glucose formation irrespective of the presence or absence of ammonia. The flux through glutamate dehydrogenase was calculated from the total alanine turnover and urea formation, and noted to be diminished in the presence of ammonia despite the increased alanine turnover. It is concluded that glutamate dehydrogenase, at least in part, controls the total alanine turnover in the absence of ammonia.