Hepatic detoxification of ammonia in the ovine liver: possible consequences for amino acid catabolism

Abstract

The effects of either low (25 μmol/min) or high (235 μmol/min) infusion of NH4Cl into the mesenteric vein for 5 d were determined on O2consumption plus urea and amino acid transfers across the portal-drained viscera (PDV) and liver of young sheep. Kinetic transfers were followed by use of15NH4Cl for 10 h on the fifth day with simultaneous infusion of [1-13C]lleucine to monitor amino acid oxidation. Neither PDV nor liver blood flow were affected by the additional NH3loading, although at the higher rate there was a trend for increased liver O2consumption. NH3-N extraction by the liver accounted for 64–70% of urea-N synthesis and at the lower infusion rate the additional N required could be more than accounted for by hepatic removal of free amino acids. At the higher rate of NH3administration additional sources of N were apparently required to account fully for urea synthesis. Protein synthesis rates in the PDV and liver were unaffected by NH3infusion but both whole-body (P< 0·05) and splanchnic tissue leucine oxidation were elevated at the higher rate of administration. Substantial synthesis of [15N]glutamine occurred across the liver, particularly with the greater NH3supply, and enrichments exceeded considerably those of glutamate. The [15N]urea synthesized was predominantly as the single labelled, i.e. [14N15N], species. These various kinetic data are compatible with the action of ovine hepatic glutamate dehydrogenase (EC1.4.1.2) in periportal hepatocytes in the direction favouring glutamate deamination. Glutamate synthesis and uptake is probably confined to the perivenous cells which do not synthesize urea. The implications of NH3detoxification to the energy and N metabolism of the ruminant are discussed.