title: Effect of chronic renal failure with metabolic acidosis on alanine metabolism in isolated liver cells.
abstract: OBJECTIVE
  Decreased ureagenesis and gluconeogenesis from alanine have been reported during chronic renal failure in rat. This study addressed the respective roles of plasma-membrane transport and intracellular metabolism in these abnormalities of alanine pathways.
  
  
  METHODS
  In hepatocytes isolated from uremic and control rats, we investigated: (1) the influence of uremia on gluconeogenesis and ureagenesis during incubations with alanine; (2) the kinetics of alanine plasma-membrane transport; (3) the relationships between intracellular alanine concentrations and its metabolism. Plasma-membrane alanine transport was assessed after addition of alanine (2 mM) by measuring its intracellular accumulation from 0 to 10 min, in the presence of a transaminase inhibitor. Alanine metabolism was studied in perifused hepatocytes by measuring intracellular alanine concentration together with urea, glucose and lactate production in the presence of increasing concentrations of alanine (0-8 mM).
  
  
  RESULTS
  Uremic rats showed decreased plasma bicarbonate. Uremia induced (P<0.05) a decrease in both gluconeogenesis (36%) and ureagenesis (22%). Alanine plasma-membrane transport decreased by 20% during uremia. During perifusions, uremia induced a 30-40% decrease in urea, glucose, and lactate production without modifying intracellular alanine concentration.
  
  
  CONCLUSIONS
  In uremic rats with acidosis, hepatocyte alanine utilization was impaired at both plasma-membrane transport and intracellular transamination steps.
authors.affiliation: Service d'Hépatogastroentérologie et de Nutrition, Clinique Résidence du Parc, Rue Gaston Berger, 13362, Marseille Cedex 10, France. njm.cano@wanadoo.fr
authors.forename: N
authors.initials: N
authors.lastname: Cano
authors.forename: J M
authors.initials: JM
authors.lastname: Sturm
authors.forename: A J
authors.initials: AJ
authors.lastname: Meijer
authors.forename: M Y
authors.initials: MY
authors.lastname: El-Mir
authors.forename: R
authors.initials: R
authors.lastname: Novaretti
authors.forename: J P
authors.initials: JP
authors.lastname: Reynier
authors.forename: X M
authors.initials: XM
authors.lastname: Leverve
mesh_terms: D000138:Acidosis / Q000150:complications / Q000378:metabolism*; D000409:Alanine / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005943:Gluconeogenesis / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014508:Urea / Q000378:metabolism*; D014511:Uremia / Q000378:metabolism
chemical_list: D014508:Urea; D000409:Alanine