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 t wo compounds and to evaluate the possible influence of the alpha KG mo iety, livers were perfused with alpha KG, Orn, ornithine alpha-ketoglu tarate (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 tot ally metabolized by the liver, whereas Arg led to Orn release (408 (SD 159) nmol/min per g liver) and a threefold stimulation of urea produc tion (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 ass ociated with Orn as OKG, it led to an increase in glutamate release an d in proline content in the liver and to a decrease in proline uptake. From these findings we conclude that (1) Arg load is extensively meta bolized by the liver, inducing urea production, (2) in enteral use, Or n supplementation appears preferable to Arg as it is less ureogenic (a s also recently demonstrated in vivo in stressed rats receiving isomol ar amounts of Arg and Orn), (3) the liver participates in the Orn-alph a KG metabolic interaction, mostly in proline metabolism, which occurs in the splanchnic area.