Effect of chronic renal failure with metabolic acidosis on alanine metabolism in isolated liver cells.
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.
Cano
N
N
Service d'Hépatogastroentérologie et de Nutrition, Clinique Résidence du Parc, Rue Gaston Berger, 13362, Marseille Cedex 10, France. njm.cano@wanadoo.fr
Sturm
J M
JM
Meijer
A J
AJ
El-Mir
M Y
MY
Novaretti
R
R
Reynier
J P
JP
Leverve
X M
XM
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
D014508:Urea; D000409:Alanine