Determination of Choline Dehydrogenase Activity along the Rat Nephron

Miller, Bernhard; Schmid, Heide; Chen, Tian Jun; Schmolke, Michael; Guder, W. G.

doi:10.1515/bchm3.1996.377.2.129

Cited by 12 publications

(8 citation statements)

References 32 publications

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“…19 For example, studies in cellular and animal systems have shown that citrulline and choline metabolism occur primarily in proximal tubular cells. [20][21][22] Kynurenic acid, as would be expected for protein-bound solutes, has been identified as a substrate for organic anion transporters (hOAT1 and hOAT3) expressed on proximal tubular cells. 23,24 Thus, elevations in plasma citrulline, choline, and kynurenic acid may signal underlying tubulointerstitial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

A Combined Epidemiologic and Metabolomic Approach Improves CKD Prediction

Rhee

Clish

Ghorbani

et al. 2013

Journal of the American Society of Nephrology

260

220

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Metabolomic approaches have begun to catalog the metabolic disturbances that accompany CKD, but whether metabolite alterations can predict future CKD is unknown. We performed liquid chromatography/mass spectrometry-based metabolite profiling on plasma from 1434 participants in the Framingham Heart Study (FHS) who did not have CKD at baseline. During the following 8 years, 123 individuals developed CKD, defined by an estimated GFR of ,60 ml/min per 1.73 m 2 . Numerous metabolites were associated with incident CKD, including 16 that achieved the Bonferroni-adjusted significance threshold of P#0.00023. To explore how the human kidney modulates these metabolites, we profiled arterial and renal venous plasma from nine individuals. Nine metabolites that predicted CKD in the FHS cohort decreased more than creatinine across the renal circulation, suggesting that they may reflect non-GFR-dependent functions, such as renal metabolism and secretion. Urine isotope dilution studies identified citrulline and choline as markers of renal metabolism and kynurenic acid as a marker of renal secretion. In turn, these analytes remained associated with incident CKD in the FHS cohort, even after adjustment for eGFR, age, sex, diabetes, hypertension, and proteinuria at baseline. Addition of a multimarker metabolite panel to clinical variables significantly increased the c-statistic (0.77-0.83, P,0.0001); net reclassification improvement was 0.78 (95% confidence interval, 0.60 to 0.95; P,0.0001). Thus, the addition of metabolite profiling to clinical data may significantly improve the ability to predict whether an individual will develop CKD by identifying predictors of renal risk that are independent of estimated GFR.

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Section: Discussionmentioning

confidence: 99%

A Combined Epidemiologic and Metabolomic Approach Improves CKD Prediction

Rhee

Clish

Ghorbani

et al. 2013

Journal of the American Society of Nephrology

260

220

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“…The normal serum betaine concentration is 20 -144 M, however, in renal medullary cells, it may be concentrated up to 50 mM [84]. However, in renal medullary cells the betaine uptake from the extracellular space by BGT-1 is the most important mechanism [86]. However, in renal medullary cells the betaine uptake from the extracellular space by BGT-1 is the most important mechanism [86].…”

Section: Genes Involved In Osmolyte Accumulationmentioning

confidence: 99%

Osmoadaptation of Mammalian Cells - An Orchestrated Network of Protective Genes

Christoph¹,

Beck²,

Neuhofer

2007

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In mammals, the cells of the renal medulla are physiologically exposed to interstitial osmolalities several-fold higher that found in any other tissue. Nevertheless, these cells not only have the ability to survive in this harsh environment, but also to function normally, which is critical for maintenance of systemic electrolyte and fluid homeostasis. Over the last two decades, a substantial body of evidence has accumulated, indicating that sequential and well orchestrated genomic responses are required to provide tolerance to osmotic stress. This includes the enhanced expression and action of immediate-early genes, growth arrest and DNA damage inducible genes (GADDs), genes involved in cell cycle control and apoptosis, heat shock proteins, and ultimately that of genes involved in the intracellular accumulation of nonperturbing organic osmolytes. The present review summarizes the sequence of genomic responses conferring resistance against osmotic stress. In addition, the regulatory mechanisms mediating the coordinated genomic response to osmotic stress will be highlighted.

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“…It is well established that betaine functions as an organic osmolyte not only in plants and bacteria but also in the renal medulla, where it helps medullary cells to survive the high osmolality of the medullary environment during antidiuresis (2,9); even bacteria growing in urine are protected against hypertonicity by taking up urinary betaine (6). In the kidney, betaine is synthesized from choline by choline dehydrogenase and betaine-aldehyde dehydrogenase in renal cortical cells (14,17,26). The highest betaine concentrations, however, are found in the renal medulla (3,30).…”

mentioning

confidence: 99%

Reabsorption of betaine in Henle's loops of rat kidney in vivo

Pummer

Dantzler²,

Lien

et al. 2000

American Journal of Physiology-Renal Physiology

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This study was designed 1) to localize and 2) to characterize betaine reabsorption from the tubular lumen in rat kidney in vivo, and 3) to test whether reabsorption is modulated by the diuretic state. [(14)C]betaine (+ [(3)H]inulin) was microperfused through the proximal convoluted tubule (PCT) and microinfused into late proximal (LP) and early distal (ED) tubules, long loops of Henle (LLH), and vasa recta of the rat in vivo et situ, and the fractional recovery of the (14)C label was determined end proximally (PCT) and in the final urine, respectively. [(14)C]betaine was not reabsorbed during ED microinfusion, whereas fractional reabsorption during LP microinfusion was 82% at 0.06 mM betaine and decreased gradually to 4.8% at 60 mM. L-Proline had lower Michaelis-Menten constant (K(m)) and sarcosine a higher K(m) than betaine. Chronic, but not acute, diuresis inhibited betaine reabsorption in Henle's loops. Fractional [(14)C]betaine reabsorption in PCT was much smaller than that during LP microinfusion. [(14)C]betaine (7.28 mM) microinfused 1) into LLH was reabsorbed to 30% and 2) into vasa recta appeared in the ipsilateral urine to a much higher extent than contralaterally. In both cases, no saturation was detected at 70 mM. We conclude that betaine is reabsorbed by mediated transport from descending limbs of short Henle's loops by a proline-preferring carrier in a diuresis-modulated manner. In the deep medulla, bidirectional blood/urine betaine transport exists.

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Determination of Choline Dehydrogenase Activity along the Rat Nephron

Cited by 12 publications

References 32 publications

A Combined Epidemiologic and Metabolomic Approach Improves CKD Prediction

A Combined Epidemiologic and Metabolomic Approach Improves CKD Prediction

Osmoadaptation of Mammalian Cells - An Orchestrated Network of Protective Genes

Reabsorption of betaine in Henle's loops of rat kidney in vivo

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