Influence of acute metabolic acidosis on the monomer and polymer forms of renal phosphate-dependent glutaminase

Hortelano, Paloma; Garcı́a-Salguero, Leticia; Lupiáñez, José A.; Alleyne, George A.O.

doi:10.1016/0024-3205(90)90505-l

Cited by 2 publications

(1 citation statement)

References 28 publications

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“…Furthermore, hepatic glutamine metabolism and glutaminase activity are being affected by perfusion of hypo-osmotic and hyper-osmotic solutions, as well as the amino acid composition of the perfusion media [29]. It has also been shown that rat renal mitochondria swell both with chronic [30, 311 and acute [32] acidosis, which at least in part, may account for the stimulated glutamine hydrolysis. Thus, it seems to be likely that also renal glutaminase is regulated in vivo by the mitochondrial matrix volume, being hormonally controlled by changes in the extracellular salt composition.…”

Section: Discussionmentioning

confidence: 99%

Effects of mitochondrial swelling and calcium on phosphate‐activated glutaminase in pig renal mitochondria

Kvamme

Roberg

Torgner

1991

European Journal of Biochemistry

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The effects of mitochondrial swelling and calcium have been used to study the possible function of the glutamine transporter in regulating glutamine hydrolysis. Salt-induced swelling of pig renal mitochondria and an iso-osmotic mixed salt solution and swelling caused by reducing the osmolarity of the incubation medium, are accompanied by activation of glutamine hydrolysis. Regulation of the glutaminase activity by salt-induced mitochondrial swelling is likely to have physiological importance, similar to the regulation of hepatic glutaminase by changing the matrix volume, that has been described by others.0.1 -1 .0 mM calcium stimulates glutamine hydrolysis and the calcium activation curve follows MichaelisMenten kinetics. The calcium activation is reversible, it is unaffected by phosphate, high glutamine and mitochondrial calcium uptake, as well as by sonication and the activation is calmodulin independent. The calcium activation is additive to that of swelling.Similar to calcium, hypo-osmotic swelling mainly increases the apparent V,,, for glutamine, whereas the apparent K, is little changed, indicating that the effects are primarily on the phosphate-activated glutaminase itself rather than on the glutamine transporter. Furthermore, calcium which activates glutamine hydrolysis, inhibits glutamine uptake into the mitochondria and so does alanine having no effect on glutamine hydrolysis. Therefore, it is indicative that glutamine transport is not rate limiting for glutamine hydrolysis.Phosphate-activated glutaminase (PAG) has an important metabolic function in the kidney as a key enzyme in ammonia production and most workers agree that the enzyme is localized to the inner mitochondrial membrane [l]. The enzyme has been purified to homogeneity from various sources; the first being from pig renal cortex [2]. Phosphate is a main activator although the enzyme is regulated by a variety of compounds among which the inhibitory reaction products glutamate and ammonia are assumed to play an essential role. In addition, acetyl-CoA activates the purified enzyme [3], whereas certain acyl-CoA derivatives activate at low concentrations and inhibit at higher ones [4]. Several authors have provided evidence for a glutamine transporter in the inner mitochondrial membrane of rat kidney and liver [S -81.In this paper we report a study of the pronounced stimulatory effect on glutamine hydrolysis by salt-induced and hypo-osmotic swelling of pig renal mitochondria. In addition, we have investigated the calcium activation of glutamine hydrolysis in renal mitochondria which previously has been found in rat brain synaptosomes [9-111. The effects of calcium and swelling have been used as tools to study the possible rate limitation of glutamine hydrolysis by the glutamine transporter.

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Section: Discussionmentioning

confidence: 99%

Effects of mitochondrial swelling and calcium on phosphate‐activated glutaminase in pig renal mitochondria

Kvamme

Roberg

Torgner

1991

European Journal of Biochemistry

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Variations in the kinetic response of several different phosphate-dependent glutaminase isozymes during acute metabolic acidosis

Hortelano

Garcı́a-Salguero

Alleyne³

et al. 1991

Mol Cell Biochem

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We describe the kinetic modifications to mitochondrial-membrane-bound phosphate-dependent glutaminase in various types of rat tissue brought about by acute metabolic acidosis. The activity response of phosphate-dependent glutaminase to glutamine was sigmoidal, showing positive co-operativity, the Hill coefficients always being higher than 2. The enzyme from acidotic rats showed increased activity at subsaturating concentrations of glutamine in kidney tubules, as might be expected, but not in brain, intestine or liver tissues. Nevertheless, when brain and intestine from control rats were incubated in plasma from acutely acidotic rats enzyme activity increased at 1 mM glutamine in the same way as in kidney cortex. The enzyme from liver tissue remained unaltered. S0.5 and nH values decreased significantly in kidney tubules, enterocytes and brain slices preincubated in plasma from acidotic rats. The sigmoidal curves of phosphate-dependent glutaminase shifted to the left without any significant changes in Vmax. The similar response of phosphate-dependent glutaminase to acute acidosis in the kidney, brain and intestine confirms the fact that enzymes from these tissues are kinetically identical and reaffirms the presence of an ammoniagenic factor in plasma, either produced or concentrated in the kidneys of rats with acute acidosis.

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Influence of acute metabolic acidosis on the monomer and polymer forms of renal phosphate-dependent glutaminase

Cited by 2 publications

References 28 publications

Effects of mitochondrial swelling and calcium on phosphate‐activated glutaminase in pig renal mitochondria

Effects of mitochondrial swelling and calcium on phosphate‐activated glutaminase in pig renal mitochondria

Variations in the kinetic response of several different phosphate-dependent glutaminase isozymes during acute metabolic acidosis

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