Concomitant synthesis and degradation of glutamine in isolated rabbit kidney tubules

Dugelay, Sylvie; Baverel, Gabriel

doi:10.1016/0304-4165(91)90251-b

Cited by 10 publications

(10 citation statements)

References 8 publications

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“…Both in the absence and the presence of acetate, the labelings of the C-1 (singlet) of glutamate and glutamine and of alanine were almost identical when [5-13 C]glutamate or [1,2-13 C]glutamate was the substrate. Tables V and VI also show that, with [5-13 C]glutamate and [1,2-13 C]glutamate as substrate, both in the absence and the presence of acetate, the labeling of the C-1 (singlet) of glutamate, glutamine, and alanine was virtually half that of the C-2 of glutamate, glutamine, and alanine when [3][4][5][6][7][8][9][10][11][12][13] C]glutamate was the substrate (see Table IV). …”

Section: As Shown Inmentioning

confidence: 88%

“…Since the C-2 and the C-3 of the oxaloacetate derived from the added [3-13 C]glutamate were converted at the same rates to the C-3 and C-2 (respectively) of the glutamate synthesized and therefore to the C-3 and C-2 of the glutamine derived from the latter glutamate, one may calculate that with glutamate as sole substrate, a mean value of 67 mol/g dry wt of glutamine arose directly from the added [3-13 C]glutamate, whereas 10.8 mol/g dry wt of [3-13 C]glutamine derived from synthesized [3][4][5][6][7][8][9][10][11][12][13] C]glutamate (see Table IV); in the presence of [3-13 C]glutamate plus acetate, the corresponding values are 34.6 and 11.3 mol/g dry wt, respectively. The latter values obtained for estimating the direct accumulation of glutamine from added [3-13 C]glutamate in the absence and the presence of acetate are in relatively good agreement with those obtained by measuring the accumulation of [5-13 C]glutamine from [5-13 C]glutamate (Table V) as well as by measuring the multiplets (spin-spin 13 C coupling of C-1 and C-2) resulting from the synthesis of [1,2-13 C]glutamine from [1,2-…”

Section: As Shown Inmentioning

confidence: 99%

“…When [3][4][5][6][7][8][9][10][11][12][13] C]glutamate was the substrate in the absence and the presence of acetate, the labeling (in mol/g dry wt) of the different carbons of glucose (␣ ϩ ␤ anomers) was as follows: C-1, 2.2 Ϯ 0.5 and 3.4 Ϯ 0.2; C-6, 1.8 Ϯ 0.5 and 2.6 Ϯ 0.1; C-2, 1.7 Ϯ 0.6 and 2.6 Ϯ 0.4; C-5, 2.5 Ϯ 0.9 and 4.5 Ϯ 0.2, respectively; the C-3 and C-4 were not enriched. When [5-13 C]-and [1,2-13 C]glutamate were the substrates, the C-3 and C-4 of glucose were enriched only in the presence of acetate; the values were 2.0 Ϯ 0.4 and 1.1 Ϯ 0.1 for the C-3, respectively; the corresponding values for the C-4 were 2.4 Ϯ 0.5 and 1.7 Ϯ 0.2, respectively.…”

Section: As Shown Inmentioning

confidence: 99%

“…However, none of the above authors measured glutamate uptake in their study. Recent studies in our laboratory (5,6) have also shown that endogenous glutamate is converted at significant rates into glutamine in isolated rabbit kidney-cortex tubules which contain a high activity of glutamine synthetase (1,(7)(8)(9), the enzyme responsible for glutamine synthesis.…”

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confidence: 98%

“…This is not surprising because the rabbit, like other herbivorous species, excretes an alkaline urine (2) that does not need to contain large amounts of ammonium ions. This also explains why rabbit kidney tubules do not readily use glutamine as substrate (5,6). By contrast, the rabbit kidney has a high capacity to trap ammonia and synthesize glutamine (1, 2, 4 -8) by pathways that are far from being fully defined.…”

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The Rabbit Kidney Tubule Simultaneously Degrades and Synthesizes Glutamate

Chauvin

Mégnin-Chanet

Martin

et al. 1997

Journal of Biological Chemistry

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The rabbit kidney does not readily metabolize but synthesizes glutamine at high rates by pathways that remain poorly defined. Therefore, the metabolism of variously labeled [13 C]-and [ 14 C]glutamates has been studied in isolated rabbit kidney tubules with and without acetate. CO 2 , glutamine, and alanine were the main carbon and nitrogenous end products of glutamate metabolism but no ammonia accumulated. Absolute fluxes through enzymes involved in glutamate metabolism, including enzymes of four different cycles operating simultaneously, were assessed by combining mainly the 13 C NMR data with a new model of glutamate metabolism. In contrast to a previous conclusion of Klahr et al. (Klahr, S., Schoolwerth, A. C., and Bourgoignie, J. J. (1972) Am. J. Physiol. 222, 813-820), glutamate metabolism was found to be initiated by glutamate dehydrogenase at high rates. Glutamate dehydrogenase also operated at high rates in the reverse direction; this, together with the operation of the glutamine synthetase reaction, masked the release of ammonia. Addition of acetate stimulated the operation of the "glutamate 3 ␣-ketoglutarate 3 glutamate" cycle and the accumulation of glucose but reduced both the net oxidative deamination of glutamate and glutamine synthesis. Acetate considerably increased flux through ␣-ketoglutarate dehydrogenase and citrate synthase at the expense of flux through phosphoenolpyruvate carboxykinase; acetate also caused a large decrease in flux through alanine aminotransferase, pyruvate dehydrogenase, and the "substrate cycle" involving oxaloacetate, phosphoenolpyruvate, and pyruvate.

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Section: As Shown Inmentioning

confidence: 88%

Section: As Shown Inmentioning

confidence: 99%

Section: As Shown Inmentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

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The Rabbit Kidney Tubule Simultaneously Degrades and Synthesizes Glutamate

Chauvin

Mégnin-Chanet

Martin

et al. 1997

Journal of Biological Chemistry

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Advantages and limitations of the use of isolated kidney tubules in pharmacotoxicology

et al. 1996

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Among the cellular models used in in vitro renal pharmacotoxicology, isolated kidney tubules, used as suspensions mainly of proximal tubules, offer important advantages. They can be prepared in large amounts under nonsterile conditions within 1-2 h; thus, it is possible to employ a great number of experimental conditions simultaneously and to obtain rapidly many experimental results. Kidney tubules can be prepared from the kidney of many animal species and also from the human kidney; given the very limited availability of healthy human renal tissue, it is therefore possible to choose the most appropriate species for the study of a particular problem encountered in man. Kidney tubules can be used for screening and prevention of nephrotoxic effects and to identify their mechanisms as well as to study the renal metabolism of xenobiotics. When compared with cultured renal cell, a major advantage of kidney tubules is that they remain differentiated. The main limitations of the use of kidney tubules in pharmacotoxicology are (1) the necessity to prepare them as soon as the renal tissue sample is obtained; (2) their limited viability, which is restricted to 2-3 h; (3) the inability to expose them chronically to a potential nephrotoxic drug; (4) the inability to study transepithelial transport; and (5) the uncertainty in the extrapolation to man of the results obtained using animal kidney tubules. These advantages and limitations of the use of human and animal kidney tubules in pharmacotoxicology are illustrated mainly by the results of experiments performed with valproate, an antiepileptic and moderately hyperammonemic agent. The fact that kidney tubules, unlike cultured renal cells, retain key metabolic properties is also shown to be of the utmost importance in detecting certain nephrotoxic effects.

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Fatty acids and glycerol or lactate are required to induce gluconeogenesis from alanine in isolated rabbit renal cortical tubules

1999

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In isolated rabbit renal cortical tubules, glucose synthesis from 1 mM alanine is negligible, while the amino acid is metabolized to glutamine and glutamate. The addition of 0.5 mM octanoate plus 2 mM glycerol induces incorporation of [U-14C]alanine into glucose and decreases glutamine synthesis, whereas oleate and palmitate in the presence of glycerol are less potent than octanoate. Gluconeogenesis is also significantly accelerated when glycerol is substituted by lactate. In view of an increase in 14CO2 fixation and elevation of both cytosolic and mitochondrial NADH/NAD+ ratios, the activation of glucose formation from alanine upon the addition of glycerol and octanoate is likely due to (i) stimulation of pyruvate carboxylation, (ii) increased availability of NADH for glyceraldehyde-3-phosphate dehydrogenase and (iii) elevation of mitochondrial redox state causing a diminished provision of ammonium for glutamine synthesis. The induction of gluconeogenesis in the presence of alanine, glycerol and octanoate is not related to cell volume changes. The results presented in this paper show the importance of free fatty acids and glycerol for regulation of renal gluconeogenesis from alanine. The possible physiological significance of the data is discussed.

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Concomitant synthesis and degradation of glutamine in isolated rabbit kidney tubules

Cited by 10 publications

References 8 publications

The Rabbit Kidney Tubule Simultaneously Degrades and Synthesizes Glutamate

The Rabbit Kidney Tubule Simultaneously Degrades and Synthesizes Glutamate

Advantages and limitations of the use of isolated kidney tubules in pharmacotoxicology

Fatty acids and glycerol or lactate are required to induce gluconeogenesis from alanine in isolated rabbit renal cortical tubules

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