Glutaminase isozymes in rat kidney

Katunuma, Nobuhiko; Tomino, Ikuko; Nishino, Hozumi

doi:10.1016/0006-291x(66)90485-2

Cited by 69 publications

(29 citation statements)

References 5 publications

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“…All the above data strongly suggest that in CRI glutamine was inadequately used by the residual functioning tissue for ammonia production. The defective use might be dependent on an altered transport of glutamine into the mitochondria, the major sites for its use (33) and/or on an inhibition of glutaminases by some "uremic toxin". It has been shown that methylguanidine inhibits rat kidney phosphate-independent glutaminase activity (34).…”

Section: Discussionmentioning

confidence: 99%

Renal metabolism of amino acids and ammonia in subjects with normal renal function and in patients with chronic renal insufficiency.

Tizianello¹,

Ferrari²,

Garibotto³

et al. 1980

J. Clin. Invest.

329

147

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A B S T R A C T The net renal metabolism of amino acids and ammonia in the post absorptive state was evaluated in subjects with normal renal functioin and in patients with chronic renal insufficiency by measuring renal uptake and release, and urinary excretion of free amino acids and ammonia. In normial subjects the kidney extracts glutamine, proline, citrulline, and phenylalanine and releases serine, arginine, taurine, threonine, tyrosine, ornithine, lysine, and perhaps alanine. The renal uptake of amino acids from arterial blood occurs by way of plasma only, whereas approximately a half of amino acid release takes place by way of blood cells. Glycine is taken up from arterial plasma, while similar amounts of this amino acid are released by way of blood cells. In the same subjects total renal ammonia production can be largely accounted for by glutamine extracted.In patients with chronic renal insufficiency (a) the renal uptake ofphenylalanine and the release oftaurine and ornithine disappear; (b) the uptake of glutamine and proline, and the release of serine and threonine are reduced by 80-90%; (c) the uptake of citrulline and the release of alanine, arginine, tyrosine, and lysine are reduced by 60-70%; (d) no exchange of glycine is detectable either by way of plasma or by way of blood cells; (e) exchange of any other amino acid via blood cells disappears, and (f) total renal ammonia production is reduced and not more than 35% of such production can be accounted for by glutamine extracted, so that alternative precursors must be used. A 140% excess of nitrogen release found in the same patients suggests an intrarenal protein and peptide breakdown, which eventually provides free amino acids for ammonia production.

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Section: Discussionmentioning

confidence: 99%

Renal metabolism of amino acids and ammonia in subjects with normal renal function and in patients with chronic renal insufficiency.

Tizianello¹,

Ferrari²,

Garibotto³

et al. 1980

J. Clin. Invest.

329

147

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“…Maleate has previously been found to activate a glutaminase activity found in kidney and other tissues which is not activated by phosphate (11,12,21). Both this activity and the phosphate-activated glutaminase were observed many years ago by Greenstein et al.…”

Section: Discussionmentioning

confidence: 92%

“…This work was supported in part by grants from t Katunuma et al (21) concluded that the phosphate-indfpendent glutaminase is not indentical to "y-glutamyl transferase." On the other hand, N. Curthoys recently suggested that the maleatestimulated phosphate-independent glutaminase might be identical or similar to y-glutamyl transpeptidase (Third International Conference on Isozymes, 1974, New Haven, Conn.).…”

Section: Discussionmentioning

confidence: 94%

“…ity is inhibited by iserine plus borate (Table 4), a reagent combination that has long been known to inhibit y-glutamyl transpeptidase (17). The* maleate-stimulated phosphateindependent glutaminase activity studied by Katunuma et al (11,21) may reflect a catalytic activity of y-glutamyl transpeptidaset. It is possible that transpeptidase plays a role in renal ammoniagenesis.…”

Section: Discussionmentioning

confidence: 94%

See 1 more Smart Citation

Stimulation of the Hydrolytic Activity and Decrease of the Transpeptidase Activity of γ-Glutamyl Transpeptidase by Maleate; Identity of a Rat Kidney Maleate-Stimulated Glutaminase and γ-Glutamyl Transpeptidase

Tate

Meister

1974

Proc. Natl. Acad. Sci. U.S.A.

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ABSTRACT-y-Glutamyl transpeptidase catalyzes transfer of the y-glutamyl moiety of glutathione (and other y-glutamyl compounds) to amino acid and peptide acceptors; this reaction probably involves (a) formation of a y-glutamyl enzyme and (b) reaction of the y-glutamyl-enzyme with an acceptor. Maleate decreases the latter reaction and markedly increases hydrolysis of the y-glutamyl donor, apparently by affecting the enzyme so as to facilitate reaction of the y-glutamyl enzyme with water. Transpeptidase catalyzes y-glutamyl hydroxamate formation from many y-glutamyl compounds and hydroxylamine; this reaction is stimulated 4-to 5-fold by maleate. Glutamine, a poor substrate for transpeptidation as compared to glutathione, is slowly hydrolyzed and converted to y-glutamyl-glutamine by the transpeptidase; in the presence of maleate, hydrolysis of glutamine is markedly (>10-fold) increased, as is also its conversion to -y-glutamyl hydroxamate in the presence of hydroxylamine. The findings suggest that the previously described "maleate-stimulated phosphate-independent glutaminase" is a catalytic function of -y-glutamyl transpeptidase. Transpeptidase-catalyzed glutaminase activity may play a role in renal ammoniagenesis. The ability of maleate to decrease transpeptidation of y-glutamyl compounds (and to increase their hydrolysis to glutamate), when considered in the light of earlier findings that treatment of animals with maleate produces aminoaciduria, is consistent with function of transpeptidase and the y-glutamyl cycle in amino-acid transport.

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“…Glutaminase (L-glutamine amidohydrolase, EC 3.5.1.2) is an intramitochondrial enzyme, found in the inner membrane or matrix fraction (3,4) and thus this reaction is also intramitochondrial. Glutaminase consists of two isoenzymes, one phosphatedependent (PDG) 1 and the other phosphate-independent (PIG) (5). PDG is probably more important than PIG in this reaction, at least in the rat, since its level in kidney is about 10 times greater than PIG (5) and it is the only one of the two in which increased levels have been demonstrated in association with the increased renal ammonia production of acidosis (6).…”

Section: Introductionmentioning

confidence: 99%