Renal Citric Acid Utilization in the Dog

Herndon, Richard F.; Freeman, Smith

doi:10.1152/ajplegacy.1958.192.2.369

Cited by 35 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The hypothesis that citrate metabolism in the renal tubular cell is closely related to urinary citrate excretion is particularly attractive because of the known avidity of the kidney for the blood citrate (19,20) and because of the demonstrated rapid metabolism of citrate by kidney tissue (13). The present experiments conclusively demonstrate an effect of acidosis and alkalosis on renal clearance of plasma citrate.…”

Section: Discussionsupporting

confidence: 61%

Effect of Acute Metabolic Acidosis and Alkalosis on Acetate and Citrate Metabolism in the Rat*

Gordon¹

1963

J. Clin. Invest.

View full text Add to dashboard Cite

An enhanced urinary excretion of citrate after administration of alkali and a diminished citrate excretion after administration of ammonium chloride were first observed by Ostberg in 1931 (1). More recently, it has been pointed out that the quantity of citrate excreted in the urine is not a direct consequence of acidification or alkalinization of the urine as believed by Ostberg, but rather is related to systemic pH (2). Hypercitraturia is associated with alkalosis and hypocitraturia with acidosis. This correlation appears to be independent of the mechanism of production of the altered acid-base balance. Thus, urinary citrate is diminished in diabetic acidosis (1, 3, 4), as a result of the intracellular acidosis of potassium depletion (5, 6), and in the metabolic acidosis induced by acetazolamide (2, 7, 8), as well as by administration of NH4Cl, CaCl, and HCl. Increased excretion of citrate in the urine has been observed during respiratory alkalosis (4, 6, 9) as well as during metabolic alkalosis.Two hypotheses have been proposed to explain this effect of altered acid-base balance on urinary citrate excretion. One hypothesis holds that alterations of pH influence the synthesis of citrate and its subsequent secretion by renal tubules (10). This implies that the intracellular pH of the renal tubular cell influences substrate metabolism in the Krebs citric acid cycle with subsequent transport of metabolites from the renal cell into the tubular urine. The second hypothesis, based on data obtained by conventional clearance techniques (11, 12), suggests that acidosis results in an increased renal tubular reabsorption of citrate and alkalosis in a decreased tubular reabsorption of filtered citrate. This would implicate membrane transport as a major mechanism affected by pH changes.It has previously been shown in this laboratory that the urinary citrate is at least in part derived from the blood citrate, since an appreciable portion of intravenously administered citrate-C14 appears unchanged in the urine (13). In the present investigations, a similar experimental approach employing radioactive tracer substances was used to study the mechanism by which acute alterations of acid-base balance influence urinary citrate excretion. These experiments support the second hypothesis, namely, that there is a pH effect on renal tubular reabsorption of filtered citrate. In addition, they provide information bearing on the origin and metabolic fate of the blood citrate in alkalosis and acidosis. MATERIALS AND METHODSFed, female, Sprague-Dawley rats weighing approximately 200 g wevere used. HCl or Na2CO3, 1.5 mmoles, was administered intragastrically in a volume of 3 ml; control animals received 3 ml of water. In all experiments, 0.3 ml of the radioactive compound was injected intravenously as a neutral solution in isotonic saline 30 minutes after administration of the test solution. Animals were restrained in wire cages, and precautions were taken to separate urine and feces during the 3-hour collection period. At the appropriate tim...

show abstract

Section: Discussionsupporting

confidence: 61%

Effect of Acute Metabolic Acidosis and Alkalosis on Acetate and Citrate Metabolism in the Rat*

Gordon¹

1963

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…In vivo studies have indicated a considerable uptake of citrate by the liver (1) and kidney (2), and a release of citrate into the blood by the peripheral tissues (1,3) and intestine (4,5). Interest in the blood citrate flux has centered primarily around the importance of this intermediate in carbohydrate metabolism, in its relationship to calcium mobilization and deposition in bone (6), and in its role as a chelating agent for calcium in the urine (7,8).…”

mentioning

confidence: 99%

The Metabolism of Citrate-C14 in Normal and in Fluoroinhibitor-Poisoned Rats*

Gordon¹

1961

J. Clin. Invest.

View full text Add to dashboard Cite

A cyclical exchange of citrate has been shown to exist in the intact organism, with the blood plasma serving as the transporting medium. In vivo studies have indicated a considerable uptake of citrate by the liver (1) and kidney (2), and a release of citrate into the blood by the peripheral tissues (1, 3) and intestine (4,5). Interest in the blood citrate flux has centered primarily around the importance of this intermediate in carbohydrate metabolism, in its relationship to calcium mobilization and deposition in bone (6), and in its role as a chelating agent for calcium in the urine (7, 8).The studies reported here have been concerned with an attempt to elucidate the metabolic fate of the blood citrate in rats with the aid of radioactive citrate. The data, obtained by following the pattern of respiratory C140, and the urinary excretion of radioactive carbon after the intravenous administration of sodium citrate-1,5-C'4, indicated a rapid turnover of the blood citrate. Three hours after injection of the labeled citrate, approximately 90 per cent of the radioactivity was recovered in the respiratory CO., and in the urinary citrate. Evidence for the utilization of blood citrate as a precursor of tissue components was provided by assaying the C14 content of protein and lipid of kidneys and liver after intravenous citrate-C14 administration.In an effort to define further the metabolic fate of the blood citrate, inhibitors of citrate oxidation were administered prior to citrate-C14 administration. Peters (9) Fed, female Sprague-Dawley rats, weighing between 185 and 235 g, were used. Citric acid-1,5-C"' was obtained from Tracerlab, Inc., and sodium acetate--C1'4 from Volk Radiochemical Co. Sodium fluoroacetate 1 was purchased from Bios Laboratories, Inc. Barium fluorocitrate, synthesized by the method of Rivett (10), was obtained from the Sonbert Chemical Co., Brooklyn, N. Y.; this preparation contained less than 1 per cent barium citrate by specific analysis. Before use, the barium salt was dissolved in dilute HCl, the barium was precipitated with saturated sodium sulfate and the supernatant fluid was neutralized with dilute NaOH. Solutions of the fluoroinhibitors were freshly prepared prior to use.In the in vivo experiments, sodium citrate-1,5-C"4 in isotonic saline was given intravenously in a volume of 0.3 ml. Collection of respiratory CO2 was accomplished by drawing CO2-free air through a glass metabolism jar containing the rat, and the respiratory CO2 was trapped in NaOH. Barium carbonate precipitates were prepared from aliquots of the NaOH solutions. After the BaCO3 was washed with water and then alcohol, it was plated and counted in a Nuclear-Chicago gas-flow counter with a Micromil window. Urine collections were made up to standard volume, and aliquots were taken for direct plating and for conversion of the carboxyl groups of the urinary citrate to CO2 with ceric sulfate (11); the CO2

show abstract

“…The mechanisms controlling renal citrate disposal are ill defined but acid-base balance, active reabsorption, or other causes could be invoked. The kidney is also particularly active in citrate synthesis (Orten and Smith 1939) and utilization (Herndon and Freeman 1958). Possibly trans-aconitate may preferentially accumulate in renal tubular cells and cause enhanced aconitase inhibition there.…”

Section: Discussionmentioning

confidence: 99%

Trans-Aconitate Utilization by Sheep

Gs¹

1968

Aust. Jnl. Of Bio. Sci.

View full text Add to dashboard Cite

SummarySheep fed diets containing 3·5 and 7· 0% trans·aconitate on a dry weight basis for 5 days appeared normal and maintained normal levels of blood citrate, ketones, and aconitate, but showed large increases in urinary citrate. Calcium and magnesium levels in plasma and urine were not substantially modified. When trans-aconitate was placed in the rumen it disappeared rapidly but did not increase the concentration of rumen volatile fatty acids; blood and urinary aconitate values remained low. trans-Aconitate did not inhibit the fermentation of soluble substrates by rumen microorganisms in vitro. Both cis-and trans-aconitate were fermented slowly.Intravenously injected sodium trans-aconitate at 1· 0 m-mole/kg body weight produced no ill effects. The citrate which subsequently accumulated in blood and urine was not a radiometabolite of [1,5-14C]trans-aconitate, suggesting that it was formed by aconitate hydratase inhibition. Plasma calcium and magnesium values were not depressed by intravenous trans-aconitate administration but urinary calcium excretion increased and urinary magnesium decreased. Under similar conditions of injection, sodium citrate was lethal.These data are believed to exclude trans-aconitate as a sole cause of lethal aconitate hydratase inhibition or of hypomagnesaemia in sheep.

show abstract

Renal Citric Acid Utilization in the Dog

Cited by 35 publications

References 0 publications

Effect of Acute Metabolic Acidosis and Alkalosis on Acetate and Citrate Metabolism in the Rat*

Effect of Acute Metabolic Acidosis and Alkalosis on Acetate and Citrate Metabolism in the Rat*

The Metabolism of Citrate-C14 in Normal and in Fluoroinhibitor-Poisoned Rats*

Trans-Aconitate Utilization by Sheep

Contact Info

Product

Resources

About