Relationship of phosphate-dependent glutaminase activity to ammonia excretion in potassium deficiency and acidosis.
Ammonia production and excretion are elevated in potassium depletion alkalosis, although normally they are reduced in alkalosis and elevated in acidosis. Studies were conducted with or without acute acid loading in normokalemic rats or rats made chronically hypokalemic with deoxycorticosterone acetate and a potassium-deficient diet to examine the role of phosphate-dependent glutaminase (PDG) in regulating ammonia excretion. Renal cortical PDG rose fourfold, and urinary ammonia excretion (UAE) doubled in potassium depletion compared to potassium-repleted controls. Following acid challenge PDG and urinary ammonia increased four- to sevenfold in both normokalemic and hypokalemic animals, but the rise in UAE did not correspond to the increase in PDG. Thus, PDG levels in acidotic normokalemic rats were one half those seen in potassium-depleted rats, but UAE in the acidotic rats was six times greater. These results could not be explained solely by changes in blood pH. The poor correlation between PDG and UAE also could not be explained by limited substrate availability, since blood glutamine levels were unaffected by potassium depletion. The disparity between UAE and PDG in potassium depletion was studied further during 9 days of potassium repletion of depleted rats. UAE was again increased by depletion but, after only 3 days of potassium repletion, UAE fell to levels found in normokalemic rats. The renal PDG activity, however, remained three times normal. Indeed, PDG remained significantly elevated even after 9 days of potassium replacement. Other enzymes involved in renal ammoniagenesis, including delta glutamyl transferase, glutamine transferase and omega deamidase, were assayed, and alterations in their activities could not account for the changes in UAE.(ABSTRACT TRUNCATED AT 250 WORDS)
D000138:Acidosis / Q000378:metabolism*; D000641:Ammonia / Q000652:urine*; D000818:Animals; D002951:Citrates / Q000652:urine; D005972:Glutaminase / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010710:Phosphates / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology / Q000627:therapeutic use; D011191:Potassium Deficiency / Q000188:drug therapy / Q000378:metabolism* / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains
D002951:Citrates; D010710:Phosphates; D011189:Potassium Chloride; D000641:Ammonia; D005972:Glutaminase