Mechanisms for the formation of alanine and aspartate on rat liver in vivo after administration of ammonium chloride.
1. The time-course of the changes in the concentrations of hepatic metabolites in response to a non-toxic load of NH(4)Cl 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.
D000409:Alanine / Q000032:analysis / Q000096:biosynthesis*; D000410:Alanine Transaminase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000643:Ammonium Chloride / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000378:metabolism; D001224:Aspartic Acid / Q000032:analysis / Q000096:biosynthesis*; D002498:Centrifugation; D003523:Cycloserine / Q000494:pharmacology; D007656:Ketoglutaric Acids / Q000032:analysis; D008099:Liver / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014508:Urea / Q000378:metabolism
D007656:Ketoglutaric Acids; D000643:Ammonium Chloride; D009243:NAD; D001224:Aspartic Acid; D009249:NADP; D000641:Ammonia; D014508:Urea; D001120:Arginine; D003523:Cycloserine; D000410:Alanine Transaminase; D000409:Alanine