Ammonia uptake by skeletal muscle in the hyperammonaemic rat


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Abstract. A two‐stage surgical occlusion of the portal vein was employed to produce hyperammonaemia in the rat. The procedure resulted in a significant rise of arterial blood ammonia level from 70·5 ± 6·5 μmol/l (mean ± SEM, n= 10) to 214·0 ± 37·7 μmol/l and in a rise of venous blood ammonia from 65·0 ± 9·4 μmol/l to 122·2 ± 7·4 μmol/l during the first day following the complete vein occlusion. A marked increase of the arteriovenous difference of ammonia concentration from virtually zero in sham‐operated controls to 72 ± 9 (n= 8) μmol/l in rats 1 day after the surgical manipulation suggested uptake of ammonia by skeletal muscle. Rat muscle glutamine synthetase activity increased from 0·46 ± 0·06 u/mg (n= 7) in controls to 2·7 ± 0·3 u/mg (n= 7) on the fourth day following portal vein ligation, and muscle branched chain amino acids aminotransferase increased from 0·2 ± 0·05 u/mg in controls to 0·96 ± 0·1 u/mg (n= 7) during the first day of ligation. Glutamine dehydrogenase and aspartate aminotransferase activities were not affected by the surgical procedure. These observations suggest that ammonia trapping in skeletal muscle is coupled to glutamine formation via amination of glutamic acid. This conclusion was further supported by the finding that ammonia uptake correlated (r= 0·92) with enahnced release of glutamine from muscle and that treatment with methionine sulfoximine, a potent inhibitor of glutamine synthetase, changed the arteriovenous difference of glutamine from –0·92 ± 0·01 mmol/l in ligated animals (net release) to ± 0·12 ± 0·01 mmol/l (net uptake) in ligated and inhibitor‐treated animals. Similarly, the inhibitor also abolished the arterio‐venous difference of ammonia. Thus, the animal model of hyperammonaemia and the muscle enzyme assays reveal that skeletal muscle is involved in the regulation of blood ammonia level by conversion of ammonia, via glutamic acid, to glutamine.

Original languageEnglish
Pages (from-to)445-450
Number of pages6
JournalEuropean Journal of Clinical Investigation
Issue number6
StatePublished - Dec 1982
Externally publishedYes


  • glutamine synthetase
  • hyperammonaemia
  • Skeletal muscle

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry


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