EFFECTS OF FLUOROCITRATE ON RENAL AMMONIAGENESIS AND GLUTAMINE-METABOLISM IN THE INTACT DOG KIDNEY

Renal glutamine metabolism was studied in vivo following infusions of fluorocitrate into chronically acidotic and alkalotic dogs. Coincident with a dramatic rise in renal cortical citrate concentrations, there was a significant fall in tissue glutamine in both acid-base states. This was accompanied by a significant increase in total renal ammonia production. Glutamine metabolism and ammoniagenesis in alkalotic dogs receiving fluorocitrate simulated that achieved in acidotic dogs. The simultaneous administration of α-ketoglutarate and fluorocitrate significantly diminished the fall in tissue glutamate and the rise in ammoniagenesis induced by fluorocitrate alone. These results are compatible with the hypothesis that ammonia production from glutamine is enhanced secondary to increased glutamate deamination. We postulate that this chain of events may be the consequence of impaired α-ketoglutarate production from citrate.