EFFECT OF PH ON AMMONIA PRODUCTION BY RENAL MITOCHONDRIA

NH3 production by renal cortical mitochondria was studied under conditons of metabolic acidosis induced in vivo and with pH manipulations of the media bathing mitochondria from normal rats. A HCO3- medium equilibrated with O2 and CO2 was utilized with glutamine concentrations of either 10 or 0.5 mM. With chronic acidosis NH3 production increased significantly at either substrate concentration. Similar results were obtained with retenone in the media, both with chronic acidosis and with acidosis of 3 h duration, indicating that increased glutamine entry and/or phosphate-dependent glutaminase (PDG) activity accounts for the increased ammoniagenesis. In contrast to acidosis induced in vivo, mitochondria from normal rats subjected to a diminution in medium pH, either by manipulation of HCO3- concentration or PCO2 [CO2 tension], significantly decrease NH3 production. Mitochondrial studies with rotenone and studies of solubilized PDG suggest that a low pH diminishes NH3 production by directly altering PDG activity. Regardless of the specifics of the mechanism, adaptation to metabolic acidosis probably is not the immediate, direct result of a change in pH.