Hepatic detoxification of ammonia in the ovine liver: possible consequences for amino acid catabolism.
The effects of either low (25 mumol/min) or high (235 mumol/min) infusion of NH4Cl into the mesenteric vein for 5 d were determined on O2 consumption plus urea and amino acid transfers across the portal-drained viscera (PDV) and liver of young sheep. Kinetic transfers were followed by use of 15NH4Cl for 10 h on the fifth day with simultaneous infusion of [1-13C]leucine to monitor amino acid oxidation. Neither PDV nor liver blood flow were affected by the additional NH3 loading, although at the higher rate there was a trend for increased liver O2 consumption. 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 NH3 administration additional sources of N were apparently required to account fully for urea synthesis. Protein synthesis rates in the PDV and liver were unaffected by NH3 infusion 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 NH3 supply, 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 (EC 1.4.1.2) 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Lobley
G E
GE
Rowett Research Institute, Bucksburn, Aberdeen.
Connell
A
A
Lomax
M A
MA
Brown
D S
DS
Milne
E
E
Calder
A G
AG
Farningham
D A
DA
D000596:Amino Acids / Q000378:metabolism*; D000643:Ammonium Chloride / Q000493:pharmacokinetics*; D000818:Animals; D005973:Glutamine / Q000096:biosynthesis; D008658:Inactivation, Metabolic; D007930:Leucine / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D009584:Nitrogen / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D012756:Sheep / Q000378:metabolism*; D014508:Urea / Q000378:metabolism
D000596:Amino Acids; D000643:Ammonium Chloride; D005973:Glutamine; D014508:Urea; D007930:Leucine; D009584:Nitrogen