Effect of chronic renal failure with metabolic acidosis on alanine metabolism in isolated liver cells

Abstract

<h2>Abstract</h2> <i>Background & aims</i>: 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. <i>Methods</i>: 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 (2mM) by measuring its intracellular accumulation from 0 to 10min, 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 (0–8mM). <i>Results</i>: Uremic rats showed decreased plasma bicarbonate. Uremia induced (<i>P</i><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. <i>Conclusions</i>: In uremic rats with acidosis, hepatocyte alanine utilization was impaired at both plasma-membrane transport and intracellular transamination steps.