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JBC, Vol. 250, Issue 19, 7728-7738, Oct, 1975
Role of anion translocation across the mitochondrial membrane in the regulation of urea synthesis from ammonia by isolated rat hepatocytes
A. J. Meijer, J. A. Gimpel, G. A. Deleeuw, J. M. Tager and J. R. Williamson
The regulation of urea synthesis from ammonia was investigated using
isolated hepatocytes from fasted rats. Addition of ammonia alone produced
only a small increase of urea formation, which was stimulated 2-fold by
ornithine in conjunction with a fall of ATP levels and an accumulation of
citrulline. Further addition of oleate or beta-hydroxybutyrate produced an
additional 2-fold stimulation of urea formation to approximately 200
mumol/g dry weight/hour. The presence of oleate also protected against the
inhibitory effect of 2,4-dinitrophenol on urea synthesis and the cellular
ATP content. The data suggest that both the rate of of energy production
and the rate of generation of reducing equivalents from endogensou
substrates are insufficient to meet the requirements for optimal rates of
urea synthesis. Urea formation from NH3 in the presence of ornithine and
oleate, but iin the absence of gluconeogenic precursors, was inhibited by
butylmalonate, a known inhibitor of malate-phosphate exchange across the
mitochondrial membrane, and stimulated by theaddition of malate and other
dicarboxylic acids and amino acids to the cell suspension...

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Copyright © 1975 by the American Society for Biochemistry and Molecular Biology.
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