Phenylpyruvate-specific glutamine transaminase and renal ammoniagenesis.
The glutaminase II ammoniagenic pathway is composed of two enzymes, glutamine transaminase (GTA) and omega-amidase. Studies herein reported define the basal activity, intrarenal distribution and response to chronic acidosis of the more active renal isoenzyme of GTA. A gradient of diminishing enzyme activity was found in assays of cortical, medullary and papillary sections (GTA activity, cortex 114 +/- 3 mumol/g/h; outer medulla 20 +/- 0.6 mumol/g/h; papilla 3 mumol/g/h). Dog kidney had much less activity while no GTA activity was found in guinea pig kidneys. In vitro acidification enhanced ammonia production by the glutaminase II pathway when studied in cytosolic preparations made from normal rat cortex. Chronic in vivo metabolic acidosis increased rat renal cortical and medullary but not papillary GTA activity by 16 and 12%, respectively. Incubation of cortical cytosolic extracts from chronically acidotic rats at pH 7.4 revealed a 29% increase in ammoniagenesis via glutaminase II, as compared to extracts from non-acidotic control rats. The cortical concentration of the most active substrate of GTA phenylpyruvate, is 343 +/- 12 mumol/kg fresh weight and its level was not influenced by in vivo acidosis. Additional studies are presented which suggest that a functional link may exist between glutaminase II and glutamate oxalacetate transaminase. This linkage could result in the cyclic utilization and reformation of phenylpyruvate while glutamine is progressively deamidated and free ammonia formed. The physiologic implications of these results are discussed.
D000641:Ammonia / Q000096:biosynthesis*; D000818:Animals; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D010667:Phenylpyruvic Acids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D000637:Transaminases / Q000378:metabolism*
D007527:Isoenzymes; D010667:Phenylpyruvic Acids; D000641:Ammonia; D000637:Transaminases; C020656:glutamine-pyruvate aminotransferase; C031606:phenylpyruvic acid