Metabolism of &lt;i&gt;p&lt;/i&gt;-Aminohippurate and its Relevance in Man

Girndt, J; Mályusz, M.; Rumpf, K. W.; Neubaur, J; Scheler, F.

doi:10.1159/000180386

Cited by 13 publications

(4 citation statements)

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“…As shown in figure I, the venous out flow contained only PAB and A-acetylated metabolites, but not PAH. This is in accord ance with results obtained in situ [14,18], Con sequently, the term 'PAH extraction ratio' is of no value in the isolated rat kidney either: 'Ei*ah', determined with the commonly used assay does not represent the fractional ex traction of PAH. It reflects a more or less complete extraction ratio of several aromatic amines.…”

Section: Discussionsupporting

confidence: 82%

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Improved Sodium and PAH Transport in the Isolated Fluorocarbon-Perfused Rat Kidney

Franke¹,

Mályusz²,

Runge³

1978

Nephron

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The effect of an artificial O₂ carrier (emulsion of the perfluorochemical FC43® with Pluronic-F-108®) on the functional capability of the isolated perfused rat kidney was tested. In control series hydroxyethyl starch (HES) instead of fluorocarbon was used. Improving O₂ supply in FC 43 experiments raised Na reabsorption to 149 µmol/g × min compared to 84.1 µmol/g × min in HES experiments. In the presence of PAH, however, Na reabsorption in FC 43 experiments was only 115 µmol/g × min. In both series, perfusion flow, calculated on the basis of Cpah, remained below the directly measured flow rate, unless analysis included all metabolites of PAH. 7V-acetylated metabolites of PAH were released at a 5 times higher rate by kidneys perfused with FC 43 than by HES-perfused organs. These results demonstrate that sufficient O₂ supply is critical both for reabsorption of Na+ and for handling of PAH. Increased tubular Na reabsorption in the absence of PAH indicates that even during perfusion with FC 43 O₂ supply is marginal.

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Section: Discussionsupporting

confidence: 82%

“…The difference between the calculated and the directly measured perfusion flow disappeared only when the PAH assay included all PAH metabolites. This implies that the validity of the C pah determination is influenced by an inconstant conversion rale of PAH as demon strated for the rat kidney in situ [18] and the human kidney [14,15].…”

Section: Discussionmentioning

confidence: 99%

Improved Sodium and PAH Transport in the Isolated Fluorocarbon-Perfused Rat Kidney

Franke¹,

Mályusz²,

Runge³

1978

Nephron

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“…It is concluded that renal hypoxia per se is an unlikely cause for the reduced N-acetylation rate of PAH. Chronic hypoxia, however, may alter renal meta bolism by increasing the renal NEFA content which, in turn, inhibits the N-acetyltransferase activity.Recently, evidence has been presented that the renal metabolism of the clearance substance /i-aminohippurate (PAH) (cleavage of the glycin-group, N-acetylation) interferes with the reliability of the determination of the plasma flow [6][7][8]13], This is predominantly due to the different distribution of PAH and of its metabolites in urine and in plasma [13] and to the circumstance that Nacetylated metabolites (N-acetyl-PAH, N-acetyl-p-aminobenzoate) remain undetected by usual chemical analysis [6,13], Furthermore, the rate of N-acetylation of PAH varies largely, as was shown in rats with experimental hypertension and in humans suffering from severe essential hypertension or from renal artery stenosis [6.8.13]. ft was found significantly reduced in the clamped kidney of rats with two-kidney Goldblatt-hypertension (one renal artery clamped, both kidneys in situ), whereas the N-acetylation rate was normal in the contralateral organ [13].…”

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Correlation between the NEFA and Acetyl-CoA Content and the N-acetylation Rate of <i>p</i>-Aminohippurate in the Kidneys of Hypertensive Goldblatt Rats. Effect of NEFA on the Renal N-acetyltransferase Activity

Mályusz¹,

Laucht²,

Gutsche³

et al. 1979

Nephron

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The cause of the reduced rate of N-acetylation of p-aminohippurate (PAH) in the clamped kidney (assumed to be hypoxic) of hypertensive, two-kidney Goldblatt rats was investigated. It was anticipated that a lower than normal activity of the enzyme acetyl-coenzyme A: arylamine-N·acetyltransferase, a reduced tissue content of acetyl-CoA or both could be the cause. The specific arylamine-N-acetyltransferase activity was significantly lower (18.6 pmol/mg protein/sec) in the clamped kidney than in the contralateral, untouched organ (28.6 pmol/mg protein/sec) or in the kidney of normotensive animals (28.3 pmol/mg protein/sec). The clamped kidney contained significantly more acetyl-CoA (32.5 nmol/g) and more non-esterified fatty acids (NEFA; determined as precursors of acetyl-CoA; 9.1 µEq/g) than the untouched kidney of Goldblatt rats (acetyl-CoA: 21.7 nmol/g, NEFA: 6.3 µEq/g) or the kidney of control animals (acetyl-CoA: 21.8 nmol/g, NEFA: 6.8 µEq/g). In the clamped kidney, a negative correlation existed between the NEFA content and the N-acetyltransferase activity. No such correlation could be found in the untouched kidney or in control kidneys. In the slightly hypoxic, isolated, Haemaccel®-perfused rat kidney (O₂ consumption: approx. 0.15 ml/g/min), the N-acetylation rate of PAH was 40–50% below normal. Addition of octanoate (arbitrarily chosen representative of NEFA) raised the O₂ consumption (and the Na reabsorption rate) significantly while reducing G > ah by circa 25% and the N-acetylation rate of PAH by circa 60%. Fatty acids with a carbon chain length of C₆-C₁₂ applied in vitro inhibited the renal N-acetyltransferase activity according to the sequence C₆ < C₈ < C₁₀ < C₁₂. It is concluded that renal hypoxia per se is an unlikely cause for the reduced N-acetylation rate of PAH. Chronic hypoxia, however, may alter renal metabolism by increasing the renal NEFA content which, in turn, inhibits the N-acetyltransferase activity.

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“…I-hippuran has become a useful tool in kinetic investigations due to the ease of its analysis (Magnusson, 1962;Pritchard, et al, 1965;Blaufox, et al, 1963). human, rabbit, pig, guinea pig, mouse, cat, cattle, sheep, and rat (Malyusz, et al, 1979;Carpenter & Mudge, 1980;Smith, et al, 1945;Despopoulos, 1956;Frindt & Vial, 1968;Setchell & Blanch, 1961;Gyrd-Hansen & Rasmussen, 1970;Cross & Taggart, 1950;Girndt, et al, 1974a and1974b), but not in dogs (Mudge & Taggart, 1950b;Newman, et al, 1949). Of these reports, only Setchell and Blanch 1961 catheter at 1, 2, 4, 6, 15, 20, 25, 30, 40, 50, 60, 75, 90, 105, and 120…”

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Evaluation of p-aminohippurate as a marker for blood-flow determinations in cattle

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Format of Dissertation 2 PART I. DETERMINATION OF PARA-AMINOHIPPURIC ACID AND N-ACETYL-PARA-AMINOHIPPURIC ACID BY HIGH PRESSURE LIQUID CHROMATOGRAPHY 4 Introduction 4 Literature Review 4 Materials and Methods 7 Materials 7 Methods 8 Detection wavelength 8 Chromatographic conditions Detector linearity Deprotelnlzatlon Barium hydroxide-zinc sulfate Perchloric acid-potassium hydroxide Peak-height evaluation Results and Discussion Detection wavelength Chromatographic condlt^on^ Detector linearity Deprotelnlzatlon Barium hydroxide-zinc sulfate Perchloric acid-potassium hydroxide Conclusions PART II. PARA-AMINOHIPPURIC ACID IN VIVO Literature Review Some techniques for the determination of flow Electromagnetic flowmeters Ultrasound flowmeters 30 Thermal methods 31 Other methods 32 General limitations Determination of blood flow by indicator-dilution 34 ill Page Renal transport of PAH PAH clearances and kinetics in vivo Metabolism of PAH Materials and Methods Experiments with non-radioactive PAH and aPAH Single injections Continuous infusions Experiments with radioactive PAH Results and Discussion Experiments with non-radioactive PAH and aPAH Single injection Continuous infusion General comments on the non-radioactive experiments.

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Metabolism of <i>p</i>-Aminohippurate and its Relevance in Man

Cited by 13 publications

References 13 publications

Improved Sodium and PAH Transport in the Isolated Fluorocarbon-Perfused Rat Kidney

Improved Sodium and PAH Transport in the Isolated Fluorocarbon-Perfused Rat Kidney

Correlation between the NEFA and Acetyl-CoA Content and the N-acetylation Rate of <i>p</i>-Aminohippurate in the Kidneys of Hypertensive Goldblatt Rats. Effect of NEFA on the Renal N-acetyltransferase Activity

Evaluation of p-aminohippurate as a marker for blood-flow determinations in cattle

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