METABOLISM OF ORNITHINE, ALPHA-KETOGLUTARATE AND ARGININE IN ISOLATED-PERFUSED RAT-LIVER

Ornithine (Orn; alpha-ketoglutarate (alpha KG) salt) and arginine (Arg) supplementation of enteral diets has been advocated in the treatment of hypercatabolism of trauma patients, but both compounds are subject to extensive hepatic metabolism. To compare the metabolism of these two compounds and to evaluate the possible influence of the alpha KG moiety, livers were perfused with alpha KG, Orn, ornithine alpha-ketoglutarate (OKG) or Arg (n 6 in each group) for 1 h. Arg uptake was nearly fourfold higher than Om uptake (690 (SD 162) v. 178 (SD 30) nmol/min per g liver), and Orn uptake was not modified by alpha KG. Orn was totally metabolized by the liver, whereas Arg led to Orn release (408 (SD 159) nmol/min per g liver) and a threefold stimulation of urea production (Arg 1.44 (SD 0.22) v. Orn 0.45 (SD 0.09) mu mol/min per g liver). alpha KG alone only increased hepatic aspartate uptake but, when associated with Orn as OKG, it led to an increase in glutamate release and in proline content in the liver and to a decrease in proline uptake. From these findings we conclude that (1) Arg load is extensively metabolized by the liver, inducing urea production, (2) in enteral use, Orn supplementation appears preferable to Arg as it is less ureogenic (as also recently demonstrated in vivo in stressed rats receiving isomolar amounts of Arg and Orn), (3) the liver participates in the Orn-alpha KG metabolic interaction, mostly in proline metabolism, which occurs in the splanchnic area.