Renal metabolic response to acid-base changes

Alleyne, George A.O.

doi:10.1172/jci106314

Cited by 81 publications

(28 citation statements)

References 23 publications

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“…The positive association between ['3C]glucose formation and 15NH3 (Fig. 6) is in good accord with the study of Alleyne [21], who found a positive correlation between NH3 and glucose formation in renal-cortical slices from acidotic rats. The calculated ratios between the rates of 15NH3 and [5-13C]glucose appearance are 1.6 and 0.8 in acidosis andcontrol respectively.…”

Section: Distribution Of 13-13c]glutamatesupporting

confidence: 91%

Metabolic fate of glutamate carbon in rat renal tubules. Studies with 13C nuclear magnetic resonance and gas chromatography-mass spectrometry

Nissim¹,

Segal²

1987

Biochemical Journal

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13C-n.m.r. spectroscopy and g.c.-m.s. were used to determine the metabolic fate of glutamate carbon in rat kidney. The main purpose was to characterize the effect of chronic metabolic acidosis on the utilization of glutamate carbon. Renal tubules obtained from normal and chronically acidotic rats were incubated in Krebs buffer, pH 7.4, in the presence of 2.5 mM-[3-13C]glutamate. During the course of incubation the concentrations of total glucose and NH3 were significantly (P less than 0.05) higher in tissue from acidotic rats. The levels of some tricarboxylic-acid-cycle intermediates were higher (P less than 0.05) in control tissue. In control tissue, 13C-n.m.r. spectra demonstrated a significantly higher rate of 13C appearance of aspartate, glutamine and [2,4-13C]glutamate. However, in acidosis the resonances of [13C]glucose carbon atoms were significantly higher. In the control, approx. 15% of glutamate carbon was accounted for by [13C]glucose formation as against 30% in chronic acidosis. However, in control tissue, 44% of glutamate carbon utilization was accounted for by recycling to glutamate and formation of aspartate, glutamine and GABA. In acidosis, only 11% was so recovered. Analysis of 15NH3 formation during the course of incubation with 2.5 mM-[15N]glutamate demonstrated a positive association between the appearance of [13C]glucose and 15NH3 both in the control and in acidosis. The data suggest that the control of gluconeogenesis and ammoniagenesis in acidosis is, in part, referable to a diminution in the rate of the reductive amination of alpha-oxoglutarate, that of the transamination reaction and that of glutamine synthesis.

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Section: Distribution Of 13-13c]glutamatesupporting

confidence: 91%

Metabolic fate of glutamate carbon in rat renal tubules. Studies with 13C nuclear magnetic resonance and gas chromatography-mass spectrometry

Nissim¹,

Segal²

1987

Biochemical Journal

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“…Pyruvate dehydrogenase may therefore be the metabolic step where fatty acids can control glucose oxidation and thereby determine the energy fuels of the kidney cortex and probably the outer medulla [44]. The crucial importance of arterial fatty acids in regulation of kidney cortex pyruvate dehydrogenase has recently been confirmed in studies on metabolic acidosis [45] where it was shown that free-fatty acid levels determine the state of kidneycortex pyruvate dehydrogenase independent from acid-base metabolism which had been shown before to regulate renal gluconeogenesis [46].…”

Section: Physiological Aspects Of Pyruvate Dehydrogenase Interconversmentioning

confidence: 99%

Metabolism of Isolated Kidney Tubules

Guder

Wieland

1974

European Journal of Biochemistry

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Pyruvate dehydrogenase activity was measured in extracts of isolated kidney cortex tubules, prepared by collagenase treatment. The measured activities were comparable to those described previously for whole kidney homogenates.Incubation of tubules in vitro in the absence of exogenous substrates led to a steady increase in enzyme activity over 30 min. This increase was not significantly changed by the addition of several gluconeogenic substrates including lactate, glutamine, glutamate, glycerol, fructose and malate. 1 mM oleate, 5 mM acetate and 20 mM 2-oxoglutarate however, prevented this increase completely. I n contrast, glucose and dihydroxyacetone accelerated the activation of pyruvate dehydrogenase during incubation in vitro. 20 mM pyruvate very rapidly activated pyruvate dehydrogenase with a following decrease below the activity of control experiments without substrate. 1 mM oleate and 20 mM 2-oxoglutarate counteracted the increase in pyruvate dehydrogenase activity caused by glucose and dihydroxyacetone and had no effect in the presence of 20 mM pyruvate.Determination of the inactive part of pyruvate dehydrogenase after addition of purified pyruvate dehydrogenase phosphatase revealed that all changes observed were probably caused by enzymatic interconversion of pyruvate dehydrogenase.The results are compared with previously published observations on the regulationlof pyruvate dehydrogenase in vivo and confirm the role of fatty acids in the regulation of kidney ,cortex pyruvate metabolism. Enzymes. Pyruvate dehydrogenase (EC 1.2.4.1) ; Arylamine acetyltransferase (EC 2.3.1.5). and kidney cortex [5,7] the mechanism by which fatty acids depressed pyruvate oxidation was a matter of speculation. Inhibition of pyruvate dehydrogenase by increased levels of acetyl-CoA [4] and an increase in reduced nicotinamide-adenine dinucleotide have been discussed as possible metabolic mediators of the action of fatty acids. Although these mechanisms have been shown to operate in isolated mitochondria [S] and with purified enzyme preparations [9], their physiological importance was hard to prove in whole cells since intracellular compartmentalization of metabolites and cofactors prevented $ a n exact interpretation of measured overall levels.The

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“…Some authors have postulated that parathyroid hormone may play a dominant role in the regulation of acid-base metabolism [41,42]. Kidney gluconeogenesis on the other hand, has been shown to be closely related to renal acid excretion [43,44]. There are however up to now no conclusive data which would confirm a direct correlation between the changes in renal gluconeogenesis under conditions of metabolic acidosis and the described effects of parathyroid hormone on renal metabolism in vitro.…”

Section: Physiological Considerationsmentioning

confidence: 99%

Metabolism of Isolated Kidney Tubules

Guder

Wieland

Stukowski

1972

European Journal of Biochemistry

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The effects of parathyroid hormone, adenosine 3' : 5'-monophosphate (Ado-3' : 5'-P) and oleate on renal metabolism have been studied in isolatcd kidney-cortex tubules from starved rats. Substrate uptake and glucose formation have been determined with L-lactate, pyruvate, glutamate, and glycerol as substrates.The results indicate that parathyroid hormone and A d o 3 : 5'-P increase renal gluconeogenesis by the same mechanism, which however, differs from the effects brough about by free fatty acids :1. Parathyroid hormone and Ado-3' : 5'-P increased glucose formation from L-lactate, pyruvate and glutamate. The stimulatory effect of parathyroid hormone was always smaller compared with thitt of Ado-3' :5'-P. Glucose formation from L-lactate was shown to be stimulated with hormone doses as low as 1 -10 nM. Oleate had an increasing effect on glucose formation from L-lactate and glycerol, but no effect on glucose formation from 10 mM pyruvate and inhibited gluconeogenesis from glutamate.2 . The stimulatory action of parathyroid hormone and Ado-3' : 5'-P was accompanied by an increase in substrate uptake, whereas oleate decreased substrate uptake.3. The effects of parathyroid hormone and Ado-3' : 5'-P on kidney-tubule metabolism were not additive, when both substances were added together.4. All effects of oleate were found to be unchanged in the presence of parathyroid hormone and Ado-3' : 5'-P or both.The results suggest two different mechanisms which may regulate renal gluconeogenesis additively .Renal gluconeogenesis has been studied in isolated perfused kidney [1,2], kidney-cortex slices [3,4] and more recently in isolated kidney tubules [5,6]. Among other metabolic pathways lipid and carbohydrate metabolism have been studied most extensively in the past 20 years. Fatty acid oxidation has been shown to be the main metabolic fuel [4,7] whereas carbohydrates were found to be oxidized to only a very small extent. In the presence of appropriate substrates gluconeogenesis could be observed a t appreciable rates which, related to tissue wet weight, may exceed those found in liver [8,9]. These results conform with the higher activities of all gluconeogenic enzymes found in the kidney [lo].

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Renal metabolic response to acid-base changes

Cited by 81 publications

References 23 publications

Metabolic fate of glutamate carbon in rat renal tubules. Studies with 13C nuclear magnetic resonance and gas chromatography-mass spectrometry

Metabolic fate of glutamate carbon in rat renal tubules. Studies with 13C nuclear magnetic resonance and gas chromatography-mass spectrometry

Metabolism of Isolated Kidney Tubules

Metabolism of Isolated Kidney Tubules

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