Glycine, a new regulator of glutamine metabolism in isolated rat-liver cells.
Glycine (0.1-10 mM) caused a dose-dependent increase in the removal of 5 mM [1-14C]glutamine by isolated rat-liver cells; at low concentrations of glycine, an increase in the formation of 14CO2, urea and glucose from glutamine occurred. At 2-10 mM, glycine also caused an accumulation of ammonia, a well-established activator of glutaminase (E.C. 3.5.1.2) and, at concentrations found in the presence of glutamine plus glycine, ammonia stimulated glutamine removal. The inhibition of urea synthesis from glutamine observed with 10 mM glycine was relieved by the addition of ornithine, suggesting that this inhibition occurred by reducing the availability of ornithine for the ornithine transcarbamoylase reaction. The metabolism of glycine as sole substrate led to a small increase in the accumulation of ammonia. Glycine did not alter hepatic glutaminase activity but swelling of rat hepatocytes, a factor considered to stimulate glutamine metabolism, was observed in the presence of glycine (1 mM). It is concluded that stimulation by glycine of hepatic utilization of glutamine is mediated by the accumulation of ammonia arising from both glycine and glutamine metabolism and by hepatocyte osmotic swelling secondary to glycine transport.
Vincent
N
N
Centre National de la Recherche Scientifique, Laboratoire de Physiologie Rénale et Métabolique, Faculté de Médecine Alexis Carrel, Lyon, France.
Martin
G
G
Baverel
G
G
D000641:Ammonia / Q000032:analysis; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002245:Carbon Dioxide / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000032:analysis; D005972:Glutaminase / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D005998:Glycine / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects; D009952:Ornithine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014508:Urea / Q000032:analysis
D000643:Ammonium Chloride; D005973:Glutamine; D002245:Carbon Dioxide; D000641:Ammonia; D014508:Urea; D009952:Ornithine; D005972:Glutaminase; D005947:Glucose; D005998:Glycine