The relationship of 4-aminobutyric acid metabolism to ammoniagenesis in renal cortex.
Mitochondrial 4-aminobutyrate aminotransferase in rat kidney can utilize pyruvate as the acceptor for the amino group of 4-aminobutyrate. Renal 4-aminobutyrate aminotransferase activity at saturating equimolar concentration of 4-aminobutyrate and 5 mM pyruvate is 42.8 +/- 2.5 mumol/g protein per h (mean +/- S.E.M.) or 70% of 4-aminobutyrate aminotransferase activity with equimolar alpha-ketoglutarate. 4-Aminobutyrate aminotransferase in brain does not transaminate with pyruvate. Since pyruvate is an important mitochondrial metabolite in kidney, net disposal of glutamate via the 4-aminobutyrate pathway is possible. The renal 4-aminobutyrate pathway in the rat has other distinctive features when compared with the pathway in rat brain. Most inhibitors of rat neuronal glutamate decarboxylase were ineffective against the renal form of the enzyme, but 20 mM semicarbazide inhibited the latter form by 80% (P < 0.001) in vitro and reduced renal 4-aminobutyrate content by 75% (P < 0.001) in vivo. In the presence of 20 mM semicarbazide, ammoniagenesis by rat renal cortex slices incubated in 1 mM glutamine was inhibited 26% (P < 0.01). Semicarbazide was proportionately less effective (15% inhibition) when ammonia-genesis was stimulated (+243%) in slices prepared from chronically acidotic animals, and was no deterrant to ammoniagenesis when non-acidotic slices were incubated in supraphysiologic concentrations of 10 mM glutamine. We conclude that whereas integrity of the renal 4-aminobutyrate pathway may contribute to glutamate disposal and thus ammoniagenesis under physiologic conditions, the pathway is a passive participant in the overall process of ammoniagenesis.
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors; D007656:Ketoglutaric Acids / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D012663:Semicarbazides / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D007656:Ketoglutaric Acids; D011773:Pyruvates; D012663:Semicarbazides; D005680:gamma-Aminobutyric Acid; D000641:Ammonia; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase