ATP Turnover and Glutamine Metabolism by Dog Kidney Tubules

2015 ◽  
pp. 78-86 ◽  
Author(s):  
C. Manillier ◽  
P. Vinay ◽  
L. Lalonde ◽  
J. Noel ◽  
A. Gougoux ◽  
...  
Keyword(s):  
Glutamine Metabolism ◽  
Kidney Tubules ◽  
Atp Turnover ◽  
Dog Kidney

scholarly journals Stimulation of glutamine metabolism by 3-aminopicolinate in isolated dog kidney-cortex tubules

1983 ◽  
Vol 210 (2) ◽  
pp. 483-487 ◽  
Author(s):  
D Durozard ◽  
G Baverel
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Glutamine Metabolism ◽  
Kidney Cortex ◽  
Kidney Tubules ◽  
Direct Stimulation ◽  
Dog Kidney ◽  
Glucose Synthesis ◽  
Isolated Dog Kidney ◽  
Gluconeogenic Substrates ◽  
Stimulation Of

1. The effects of 3-aminopicolinate, a known hyperglycaemic agent in the rat, on glutamine metabolism were studied in isolated dog kidney tubules. 2. 3-Aminopicolinate greatly stimulated glutamine (but not glutamate) removal and glutamate accumulation from glutamine as well as formation of ammonia, aspartate, lactate, alanine and glucose. 3. The increased accumulation of aspartate from glutamine and glutamate, and the inhibition of glucose synthesis from various non-nitrogenous gluconeogenic substrates, as well as the increased accumulation of malate from succinate, support the proposal that 3-aminopicolinate is an inhibitor rather than a stimulator of phosphoenolpyruvate carboxykinase (EC 4.1.1.32) in dog kidney tubules. 4. With glutamine as substrate, the increase in flux through glutamate dehydrogenase (EC 1.4.1.3) could not explain the large increase in glutamine removal caused by 3-aminopicolinate. 5. Inhibition by amino-oxyacetate of accumulation of aspartate and alanine from glutamine caused by 3-aminopicolinate did not prevent the acceleration of glutamine utilization. 6. These data are consistent with a direct stimulation of glutaminase (EC 3.5.1.2) by 3-aminopicolinate in dog kidney tubules.

ATP turnover and renal response of dog tubules to pH changes in vitro

1986 ◽  
Vol 251 (5) ◽  
pp. F919-F932
Author(s):  
C. Manillier ◽  
P. Vinay ◽  
L. Lalonde ◽  
A. Gougoux
Keyword(s):  
Respiratory Acidosis ◽  
Maximum Activity ◽  
Tissue Response ◽  
Proximal Tubules ◽  
Glutamine Metabolism ◽  
Ammonia Production ◽  
Atp Turnover ◽  
Dog Kidney

In vivo the dog kidney responds to metabolic or respiratory acidosis by a marked increment of its ammonia production (expressed per 100 milliliters glomerular filtration rate). This phenomenon is related to a switch from metabolic utilization of nonammoniagenic (lactate) to ammoniagenic (glutamine) substrates to support ATP turnover in the proximal tubules. We have proposed that in vivo the maximum activity of the ammoniagenic process is fixed by the ATP turnover in this segment of the nephron. The maximal glutamine metabolism is reached when 100% of this turnover is supported by glutamine metabolism. We have studied how these concepts apply to the adaptation of glutamine metabolism and ammonia production to a low pH in vitro using proximal tubules of dogs incubated when one (lactate or glutamine) or several (glutamine plus lactate or plus palmitate) substrates are provided. At pH 7.4 glutamine alone supports already 71-76% of the tissue ATP turnover (minimal and maximal values). With acidification this fraction rises to nearly 87-94%, but this increases only modestly the ammonia production. Reducing the ATP turnover with ouabain at pH 7.4 decreases the absolute glutamine utilization, which now supports only 45-50% of the ATP turnover. Again acidification increases this fraction to 90-99%. Addition of lactate with glutamine displaces part of the glutamine metabolized, but greatly stimulates the synthesis of alanine. Fatty acids depress ammonia production and blunt the tissue response to acidification. Gluconeogenesis from lactate is minimally influenced by incubation pH. It is concluded that the ATP turnover limits the metabolism of glutamine by proximal tubules in vitro as in vivo in the dog, and that the response to acidification is small in vitro because of the absence of alternative substrates.

Regulation of glutamine metabolism in dog kidney cortex: effect of pH and chronic acidosis

1992 ◽  
Vol 262 (6) ◽  
pp. F1007-F1014
Author(s):  
A. C. Schoolwerth ◽  
B. C. Smith ◽  
K. Drewnowska
Keyword(s):  
Glutamate Dehydrogenase ◽  
Mitochondrial Membrane ◽  
Glutamine Metabolism ◽  
Kidney Cortex ◽  
Cytosolic Ph ◽  
Isolated Mitochondria ◽  
Significant Difference ◽  
Dog Kidney ◽  
Ammonium Production ◽  
Krebs Henseleit Buffer

To examine the interrelationships of proton compartmentation and ammoniagenesis, experiments were performed in tubules and mitochondria isolated from dog kidney cortex. Tubules were incubated in Krebs-Henseleit buffer at different pH (pHe), and cytosolic pH (pHi) was estimated with the fluorescent probe 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Mitochondrial pH (pHm) was determined simultaneously in intact tubules by use of dimethyloxazolidine-2,4-dione. Over the pHe range 6.9-7.7, pHi was similar in control and acidotic dogs and linearly related to pHe. At pHe 7.4 in control tubules. pHm was 7.78 +/- 0.07, and varied little over the pHe range of 7.0-7.7. The pH gradient across the mitochondrial membrane rose at acid pHe. pHm was more alkaline when estimated in tubules from acidotic dogs compared with controls. Ammonium and glucose productions from glutamine were inversely related to pHe and pHi in tubules from both control and acidotic animals and were higher in acidosis. In contrast, ammonium production by isolated mitochondria did not vary as pHe was altered. Enzyme fluxes, calculated from metabolite changes, demonstrated that glutamate dehydrogenase (GDH) flux was altered. Enzyme fluxes, calculated from metabolite changes, demonstrated that glutamate dehydrogenase (GDH) flux was inversely and glutaminase (PDG) flux was linearly related to pHe. Ammonium production was significantly greater in mitochondria from acidotic dogs because of accelerated flux through PDG but not GDH. The present study demonstrates significant difference between proton compartmentation and regulation of ammoniagenesis in kidneys from acidotic dog compared with rat.

scholarly journals A role for bicarbonate in the regulation of mammalian glutamine metabolism

1979 ◽  
Vol 184 (3) ◽  
pp. 599-606 ◽  
Author(s):  
G Baverel ◽  
P Lund
Keyword(s):  
Rat Kidney ◽  
Glutamine Metabolism ◽  
Kidney Cortex ◽  
Complete Oxidation ◽  
Kidney Tubules ◽  
Acid Base Balance ◽  
Acid Base ◽  
Rat Kidney Cortex ◽  
Base Balance

1. The concentration of HCO3- (independent of any change of pH) exerts different effects on glutamine metabolism in rat kidney-cortex tubules, hepatocytes and enterocytes.2. In kidney tubules HCO3- (10.5-50 MM) has no effect on glutaminase (EC 3.5.1.2), whereas glutamate dehydrogenase (EC 1.4.1.3) is inhibited as HCO3- concentration is increased. The result is that flux through the entire glutamate-to-glucose pathway is inhibited by increasing HCO3- concentrations. A large proportion (more than 30%) of the glutamine removed undergoes complete oxidation. 3. In hepatocytes, and to a smaller extent in enterocytes, HCO3- is an accelerator of glutaminase. Synthesis of glucose and urea from glutamine in hepatocytes increases as HCO3- concentration is increased. Calculations show that fumarate, formed via aspartate aminotransferase and arginino-succinate lyase, is the precursor of the glucose. There is no complete oxidation of the carbon skeleton of glutamine in hepatocytes. 4. Leucine at near-physiological concentrations (0.1-1 mM) is an accelerator of glutaminase in hepatocytes, but not in kidney tubules or in enterocytes. 5. The results are discussed in relation to regulation of acid/base balance in vivo.

scholarly journals Effects of fluorocitrate on renal ammoniagenesis and glutamine metabolism in the intact dog kidney

1979 ◽  
Vol 15 (3) ◽  
pp. 255-263 ◽  
Author(s):  
Edmund Bourke ◽  
Gustavo Frindt ◽  
George E. Schreiner ◽  
Harry G. Preuss
Keyword(s):  
Glutamine Metabolism ◽  
Dog Kidney

scholarly journals Complexity of glutamine metabolism in kidney tubules from fed and fasted rats

2004 ◽  
Vol 378 (2) ◽  
pp. 485-495 ◽  
Author(s):  
Barbara VERCOUTÈRE ◽  
Daniel DUROZARD ◽  
Gabriel BAVEREL ◽  
Guy MARTIN
Keyword(s):  
Glutamine Synthetase ◽  
Reductive Amination ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Glutamine Metabolism ◽  
Kidney Tubules ◽  
Nmr Data ◽  
Energy Provider ◽  
Concomitant Operation ◽  
Fasted Rats

Glutamine is an important renal glucose precursor and energy provider. In order to advance our understanding of the underlying metabolic processes, we studied the metabolism of variously labelled [13C]glutamine and [14C]glutamine molecules and the effects of fasting in isolated rat renal proximal tubules. Absolute fluxes through the enzymes involved, including enzymes of four different cycles operating concomitantly, were assessed by combining mainly the 13C NMR data with an appropriate model of glutamine metabolism. In both nutritional states, unidirectional glutamine removal by glutaminase was partially masked by the concomitant operation of glutamine synthetase; fasting accelerated glutamine removal by increasing flux solely through glutaminase, without changing that through glutamine synthetase. Fasting stimulated net glutamate degradation only by decreasing flux through glutamate dehydrogenase in the reductive amination direction, but surprisingly did not significantly alter complete oxidation of the glutamine carbon skeleton. Finally, gluconeogenesis from glutamine involved not only substantial recycling through the tricarboxylic acid cycle, but also an important anaplerotic flux through pyruvate carboxylase that was accelerated dramatically by fasting. Thus renal glutamine metabolism follows an unexpectedly complex route that is precisely regulated during fasting.

scholarly journals Regulation of glutamine metabolism in dog kidney in vivo

1986 ◽  
Vol 29 (1) ◽  
pp. 68-79 ◽  
Author(s):  
Patrick Vinay ◽  
Guy Lemieux ◽  
André Gougoux ◽  
Mitchell Halperin
Keyword(s):  
Glutamine Metabolism ◽  
Dog Kidney

Maleate-induced stimulation of glutamine metabolism in the intact dog kidney

1985 ◽  
Vol 248 (4) ◽  
pp. F585-F593
Author(s):  
A. Gougoux ◽  
P. Vinay ◽  
M. Duplain
Keyword(s):  
Filtration Rate ◽  
Glutamine Metabolism ◽  
Renal Metabolism ◽  
Glutamate Concentration ◽  
Metabolic Block ◽  
Dog Kidney ◽  
Total Ammonia ◽  
Lactate Utilization ◽  
Alpha Ketoglutarate Dehydrogenase ◽  
Stimulation Of

Studies were performed in anesthetized normal dogs to evaluate the effects of maleate on renal metabolism. Intravenous administration of maleate (50 mg/kg) markedly increased urinary excretion of glutamine, glutamate, alpha-ketoglutarate, alanine, lactate, pyruvate, and citrate. Despite a fourfold rise in renal cortical concentration of alpha-ketoglutarate, glutamine utilization expressed per 100 ml glomerular filtration rate almost doubled following maleate administration, whereas total ammonia production increased threefold, most of this ammonia being diverted into the renal vein. The renal production of alpha-ketoglutarate rose in a spectacular fashion and was almost equal to the renal utilization of glutamine, indicating a metabolic block at the alpha-ketoglutarate dehydrogenase step. Maleate reduced renal alanine production but did not change lactate utilization. These findings suggest that 1) in the intact dog the mitochondrial entry of glutamine is not regulated only by alpha-ketoglutarate; 2) the deamination of glutamate into alpha-ketoglutarate is accelerated by maleate, probably through an impaired mitochondrial NADH production; 3) the resulting decrement in intramitochondrial glutamate concentration deinhibits the phosphate-dependent glutaminase.

Cationic excretion by the dog kidney

1960 ◽  
Vol 198 (5) ◽  
pp. 1053-1055 ◽  
Author(s):  
Floyd R. Domer
Keyword(s):  
Potassium Salt ◽  
Transport Systems ◽  
Organic Cations ◽  
Renal Tubules ◽  
Kidney Tubules ◽  
Before And After ◽  
Dog Kidney ◽  
Potassium Secretion ◽  
Renal Tubular ◽  
Close Interrelationship

The cells of the renal tubules are known to secrete both organic cations and potassium. A method of demonstrating potassium secretion is to force feed a potassium salt for a period of time and then infuse potassium during a clearance experiment. In these experiments the organic cations, tolazoline (Priscoline), N'-methylnicotinamide (NMN) and mepiperphenidol (Darstine) were force fed to dogs. The effects on cationic excretion during standard clearance experiments before and after this procedure indicated an increased efficiency of the renal tubular handling of Priscoline and NMN but not of Darstine. In animals force fed potassium chloride there was also an increased efficiency in the handling of mecamylamine (Inversine). These results add further evidence to the close interrelationship of the transport systems involved in the secretion of potassium and organic cations by the kidney tubules.

Sign in / Sign up

Export Citation Format

Share Document