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

Gerald Lobley, A Connell, Michael A. Lomax, David Stanley Brown, Eric Milne, Alexander Graham Calder, D A Farningham

Research output: Contribution to journalArticle

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Abstract

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)
Original languageEnglish
Pages (from-to)667-85
Number of pages19
JournalBritish Journal of Nutrition
Volume73
Issue number5
Publication statusPublished - 1 May 1995

Fingerprint

Ammonia
Sheep
Amino Acids
Viscera
Liver
Urea
Glutamic Acid
Glutamate Dehydrogenase
Leucine
Mesenteric Veins
Deamination
Glutamine
Hepatocytes
Proteins

Keywords

  • Amino Acids
  • Ammonium Chloride
  • Animals
  • Glutamine
  • Leucine
  • Liver
  • Male
  • Metabolic Detoxication, Drug
  • Nitrogen
  • Oxygen Consumption
  • Sheep
  • Urea

Cite this

Lobley, G., Connell, A., Lomax, M. A., Brown, D. S., Milne, E., Calder, A. G., & Farningham, D. A. (1995). Hepatic detoxification of ammonia in the ovine liver: possible consequences for amino acid catabolism. British Journal of Nutrition, 73(5), 667-85.

Hepatic detoxification of ammonia in the ovine liver: possible consequences for amino acid catabolism. / Lobley, Gerald; Connell, A; Lomax, Michael A.; Brown, David Stanley; Milne, Eric; Calder, Alexander Graham; Farningham, D A.

In: British Journal of Nutrition, Vol. 73, No. 5, 01.05.1995, p. 667-85.

Research output: Contribution to journalArticle

Lobley, G, Connell, A, Lomax, MA, Brown, DS, Milne, E, Calder, AG & Farningham, DA 1995, 'Hepatic detoxification of ammonia in the ovine liver: possible consequences for amino acid catabolism', British Journal of Nutrition, vol. 73, no. 5, pp. 667-85.
Lobley, Gerald ; Connell, A ; Lomax, Michael A. ; Brown, David Stanley ; Milne, Eric ; Calder, Alexander Graham ; Farningham, D A. / Hepatic detoxification of ammonia in the ovine liver: possible consequences for amino acid catabolism. In: British Journal of Nutrition. 1995 ; Vol. 73, No. 5. pp. 667-85.
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T1 - Hepatic detoxification of ammonia in the ovine liver: possible consequences for amino acid catabolism

AU - Lobley, Gerald

AU - Connell, A

AU - Lomax, Michael A.

AU - Brown, David Stanley

AU - Milne, Eric

AU - Calder, Alexander Graham

AU - Farningham, D A

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N2 - 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)

AB - 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)

KW - Amino Acids

KW - Ammonium Chloride

KW - Animals

KW - Glutamine

KW - Leucine

KW - Liver

KW - Male

KW - Metabolic Detoxication, Drug

KW - Nitrogen

KW - Oxygen Consumption

KW - Sheep

KW - Urea

M3 - Article

VL - 73

SP - 667

EP - 685

JO - British Journal of Nutrition

JF - British Journal of Nutrition

SN - 0007-1145

IS - 5

ER -