Adaptive ammoniagenesis in chronic renal failure.
The role of gamma-glutamyltransferase (gamma-GT) in renal ammoniagenesis, glutamine (Gln), and glutathione (GSH) utilization was evaluated in the intact functioning rat kidney of subtotal nephrectomy (SNX) model of chronic renal failure (CRF). NH4+ derived from extracellular gamma-GT hydrolysis of Gln and GSH was differentiated from the intramitochondrial phosphate-dependent glutaminase by using acivicin, a gamma-GT-specific inhibitor. In the control (C) group Gln extraction accounted for 61% of total NH4+ production (sum of renal venous and urinary NH4+), but only 41% in SNX group. In the SNX group GSH extraction accounted for 10% of total NH4+ production, but only 1% in the C group. Acivicin inhibited 44% and 33% of total NH4+ production in SNX and C group respectively, as compared to baseline before acivicin. In CRF, gamma-GT a key enzyme of the gamma-glutamyl cycle plays a significant role in adaptive ammoniagenesis.
Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock.
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D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D000963:Antimetabolites; D005972:Glutaminase / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D009392:Nephrectomy; D051381:Rats; D011919:Rats, Inbred Strains; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000963:Antimetabolites; D007555:Isoxazoles; D005973:Glutamine; D000641:Ammonia; D005723:gamma-Glutamyltransferase; D005972:Glutaminase; D005978:Glutathione; C006303:acivicin