HEPATIC DETOXIFICATION OF AMMONIA IN THE OVINE LIVER - POSSIBLE CONSEQUENCES FOR AMINO-ACID CATABOLISM

The effects of either low (25 mu mol/min) or high (235 mu mol/min) inf usion of NH4Cl into the mesenteric vein for 5 d were determined on O-2 consumption plus urea and amino acid transfers across the portal-drai ned viscera (PDV) and liver of young sheep. Kinetic transfers were fol lowed by use of (NH4Cl)-N-15 for 10 h on the fifth day with simultaneo us infusion of [1-C-13]leucine to monitor amino acid oxidation. Neithe r PDV nor liver blood flow were affected by the additional NH3 loading , although at the higher rate there was a trend for increased liver O- 2 consumption. NH3-N extraction by the liver accounted for 64-70 % of urea-N synthesis and at the lower infusion rate the additional N requi red could be more than accounted for by hepatic removal of free amino acids. At the higher rate of NH3 administration additional sources of N were apparently required to account fully for urea synthesis. Protei n synthesis rates in the PDY and liver were unaffected by NH3 infusion but both whole-body (P < 0.05) and splanchnic tissue leucine oxidatio n were elevated at the higher rate of administration. Substantial synt hesis of [N-15]glutamine occurred across the liver, particularly with the greater NH3 supply, and enrichments exceeded considerably those of glutamate. The [N-15]urea synthesized was predominantly as the single labelled, i.e. [(NN)-N-14-N-15], species. These various kinetic data are compatible with the action of ovine hepatic glutamate dehydrogenas e (EC 1.4.1.2) in periportal hepatocytes in the direction favouring gl utamate deamination. Glutamate synthesis and uptake is probably confin ed to the perivenous cells which do not synthesize urea. The implicati ons of NH3 detoxification to the energy and N metabolism of the rumina nt are discussed.