Effects of 2-Oxoglutarate Concentrations on Canine Slice Ammoniagenesis

Abstract

The concentration of renal 2-oxoglutarate has been proposed as an important regulator of ammoniagenesis in dog kidneys. In the present study, canine kidney slices produced less ammonia from glutamine and glutamate when 2-oxoglutarate was present in the incubation medium. However, the addition of arsenite, a metabolic blocker known to block 2-oxoglutarate metabolism and lead to its accumulation, overcame 2-oxoglutarate inhibition of ammoniagenesis when glutamine and glutamate were the ammonia precursors. Therefore, metabolism of 2-oxoglutarate, rather than its concentration, governed ammonia production from glutamine and glutamate in incubating dog renal tissue. In contrast to the results with 2-oxoglutarate, inhibition of glutamine ammoniagenesis by glutamate was not overcome by arsenite. The results suggest that renal ammonia adaptation in acidotic dogs cannot be ascribed to a theory based upon 2-oxoglutarate concentrations controlling the direction of the glutamate dehydrogenase pathway (GDH), decreasing glutamine transport, or directly inhibiting GDH enzyme activity.