Conversion of [15N]ammonia into urea and amino acids in humans and the effect of nutritional status

P J Weijs, Alexander Graham Calder, Eric Milne, Gerald Lobley

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Hepatic NH3 detoxification by ureagenesis requires an input of aspartate-N, originating either from amino acid-N or NH3-N. The relative importance of these two routes may depend on the nutritional state. To test this, four volunteers were given a liquid diet for 2 d and then on day 3 were either fed every 20 min or fasted. Doses of 15NH4Cl were taken orally every 20 min for 6 h (total 1.5 g) and blood was sampled hourly. Urea-N elimination under fasted conditions was only 0.75 of that for the fed state. Considering the increase in body urea pool during feeding, ureagenesis during fasting was probably closer to 0.6 of that during feeding. Since the [14N15N]urea enrichment was not different between the fed and fasted states, the proportion of the 15NH3 dose converted to urea during fasting was also 0.6 of that during the fed condition. No change in [14N15N]urea and [amide-15N]glutamine enrichment suggested that NH3 enrichment was also not affected by nutritional state. Enrichment of [15N15N]urea was approximately 0.05 that of [14N15N]urea which indicates that 15NH3 can also enter the aspartate route, the importance of which is yet unknown. Both [15N15N]urea and [amino-15N]glutamine enrichment in the fasted state were approximately 1.7 times that in the fed state, indicating increased labelling of precursors and/or increased NH3 flux through the aspartate route. Glutamate, valine, leucine and isoleucine showed comparable increases in enrichment during fasting. Arginine enrichment was unaltered by nutritional state, but was lower than [14N15N]urea, indicating incomplete equilibration with the arginine pool in periportal hepatocytes. The present study indicates that hepatic NH3 detoxification may use the aspartate route, gaining importance in the fasted state. The majority of urea was supplied with only one N atom from NH3, thus provision of the other may have consequences for alternative substrates, in particular amino acids.
Original languageEnglish
Pages (from-to)491-9
Number of pages9
JournalBritish Journal of Nutrition
Volume76
Issue number4
Publication statusPublished - 1 Oct 1996

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Nutritional Status
Ammonia
Urea
Amino Acids
Aspartic Acid
Fasting
Glutamine
Arginine
Isoleucine
Liver
Valine
Amides
Leucine
Glutamic Acid
Volunteers
Hepatocytes
Diet

Keywords

  • Adult
  • Amino Acids
  • Ammonia
  • Ammonium Chloride
  • Aspartic Acid
  • Cross-Over Studies
  • Fasting
  • Glutamine
  • Humans
  • Intestinal Mucosa
  • Nitrogen
  • Nitrogen Isotopes
  • Nutritional Status
  • Urea

Cite this

Conversion of [15N]ammonia into urea and amino acids in humans and the effect of nutritional status. / Weijs, P J; Calder, Alexander Graham; Milne, Eric; Lobley, Gerald.

In: British Journal of Nutrition, Vol. 76, No. 4, 01.10.1996, p. 491-9.

Research output: Contribution to journalArticle

Weijs, P J ; Calder, Alexander Graham ; Milne, Eric ; Lobley, Gerald. / Conversion of [15N]ammonia into urea and amino acids in humans and the effect of nutritional status. In: British Journal of Nutrition. 1996 ; Vol. 76, No. 4. pp. 491-9.
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T1 - Conversion of [15N]ammonia into urea and amino acids in humans and the effect of nutritional status

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N2 - Hepatic NH3 detoxification by ureagenesis requires an input of aspartate-N, originating either from amino acid-N or NH3-N. The relative importance of these two routes may depend on the nutritional state. To test this, four volunteers were given a liquid diet for 2 d and then on day 3 were either fed every 20 min or fasted. Doses of 15NH4Cl were taken orally every 20 min for 6 h (total 1.5 g) and blood was sampled hourly. Urea-N elimination under fasted conditions was only 0.75 of that for the fed state. Considering the increase in body urea pool during feeding, ureagenesis during fasting was probably closer to 0.6 of that during feeding. Since the [14N15N]urea enrichment was not different between the fed and fasted states, the proportion of the 15NH3 dose converted to urea during fasting was also 0.6 of that during the fed condition. No change in [14N15N]urea and [amide-15N]glutamine enrichment suggested that NH3 enrichment was also not affected by nutritional state. Enrichment of [15N15N]urea was approximately 0.05 that of [14N15N]urea which indicates that 15NH3 can also enter the aspartate route, the importance of which is yet unknown. Both [15N15N]urea and [amino-15N]glutamine enrichment in the fasted state were approximately 1.7 times that in the fed state, indicating increased labelling of precursors and/or increased NH3 flux through the aspartate route. Glutamate, valine, leucine and isoleucine showed comparable increases in enrichment during fasting. Arginine enrichment was unaltered by nutritional state, but was lower than [14N15N]urea, indicating incomplete equilibration with the arginine pool in periportal hepatocytes. The present study indicates that hepatic NH3 detoxification may use the aspartate route, gaining importance in the fasted state. The majority of urea was supplied with only one N atom from NH3, thus provision of the other may have consequences for alternative substrates, in particular amino acids.

AB - Hepatic NH3 detoxification by ureagenesis requires an input of aspartate-N, originating either from amino acid-N or NH3-N. The relative importance of these two routes may depend on the nutritional state. To test this, four volunteers were given a liquid diet for 2 d and then on day 3 were either fed every 20 min or fasted. Doses of 15NH4Cl were taken orally every 20 min for 6 h (total 1.5 g) and blood was sampled hourly. Urea-N elimination under fasted conditions was only 0.75 of that for the fed state. Considering the increase in body urea pool during feeding, ureagenesis during fasting was probably closer to 0.6 of that during feeding. Since the [14N15N]urea enrichment was not different between the fed and fasted states, the proportion of the 15NH3 dose converted to urea during fasting was also 0.6 of that during the fed condition. No change in [14N15N]urea and [amide-15N]glutamine enrichment suggested that NH3 enrichment was also not affected by nutritional state. Enrichment of [15N15N]urea was approximately 0.05 that of [14N15N]urea which indicates that 15NH3 can also enter the aspartate route, the importance of which is yet unknown. Both [15N15N]urea and [amino-15N]glutamine enrichment in the fasted state were approximately 1.7 times that in the fed state, indicating increased labelling of precursors and/or increased NH3 flux through the aspartate route. Glutamate, valine, leucine and isoleucine showed comparable increases in enrichment during fasting. Arginine enrichment was unaltered by nutritional state, but was lower than [14N15N]urea, indicating incomplete equilibration with the arginine pool in periportal hepatocytes. The present study indicates that hepatic NH3 detoxification may use the aspartate route, gaining importance in the fasted state. The majority of urea was supplied with only one N atom from NH3, thus provision of the other may have consequences for alternative substrates, in particular amino acids.

KW - Adult

KW - Amino Acids

KW - Ammonia

KW - Ammonium Chloride

KW - Aspartic Acid

KW - Cross-Over Studies

KW - Fasting

KW - Glutamine

KW - Humans

KW - Intestinal Mucosa

KW - Nitrogen

KW - Nitrogen Isotopes

KW - Nutritional Status

KW - Urea

M3 - Article

VL - 76

SP - 491

EP - 499

JO - British Journal of Nutrition

JF - British Journal of Nutrition

SN - 0007-1145

IS - 4

ER -