1. The time-course of the changes in the concentrations of hepatic metabolites in response to a non-toxic load of NH4Cl were measured in fed and starved rats. 2. There was a rapid increase (after 2min) in [alanine] and [aspartate] which remained high for 10–15min; the absolute increase in [alanine] was smaller in starved rats. 3. These changes were accompanied by a decrease in [oxoglutarate] and in the [3-hydroxybutyrate]/[acetoacetate] ratio. 4. Prior administration of l-arginine to fed rats resulted in smaller increases in [alanine] and [aspartate] after the ammonia load. This is presumably due to stimulation of the urea cycle. 5. Increased formation of alanine in starved rats occurred after prior administration of dihydroxyacetone to increase the availability of pyruvate. 6. Administration of l-cycloserine, an inhibitor of glutamate–alanine aminotransferase, completely prevented the increase in [alanine] after the ammonia load; in this case the absolute increase in [aspartate] was higher. 7. [Oxoglutarate], [citrate] and [isocitrate] at 25min after the ammonia load were higher than the initial concentrations, but returned to normal by 50min. It is suggested that this `overshoot' may be due to temporary compartmentation of oxoglutarate. 8. The mechanisms and physiological significance of alanine and aspartate formation in these experiments are discussed.
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Research Article|
March 01 1974
Mechanisms for the formation of alanine and aspartate on rat liver in vivo after administration of ammonium chloride
John T. Brosnan;
John T. Brosnan
1Metabolic Research Laboratory, Nuffield Department of Clinical Medicine, Radcliffe Infirmary, Oxford OX2 6HE, U.K.
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Dermot H. Williamson
Dermot H. Williamson
1Metabolic Research Laboratory, Nuffield Department of Clinical Medicine, Radcliffe Infirmary, Oxford OX2 6HE, U.K.
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Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 1974 London: The Biochemical Socity
1974
Biochem J (1974) 138 (3): 453–462.
Citation
John T. Brosnan, Dermot H. Williamson; Mechanisms for the formation of alanine and aspartate on rat liver in vivo after administration of ammonium chloride. Biochem J 1 March 1974; 138 (3): 453–462. doi: https://doi.org/10.1042/bj1380453
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