Role of hippurate in acidosis induced adaptation in renal γ-glutamyltransferase

Abstract

Metabolic acidosis results in an adaptation in renal γ-glutamyltransferase (γ-GT) and a doubling of hippurate excretion. The greater rate of γ-glutamohydroxamate, γ-GHA, formation from L-glutamine, but not from glutathione, by acidotic kidney homogenates suggest an increased γ-glutamyl-enzyme complex formation and a preference for glutamine as the γ-glutamyl donor in acidosis. Hippurate added in vitro to cortical homogenates or microsomes mimics the affect of acidosis upon γ-GHA formation from glutamine. Acid extracts of urine stimulated ammonia formation from glutamine using cortical microsomes in agreement with the measured hippurate levels. Administering an exogenous hippurate load to fasting nonacidotic rats doubled ammonia excretion and the rate of γ-GHA formation by cortical homogenates. These results are consistent with the acidosis induced adaptation in renal γ-GT governed by hippurate.