The site of metabolism of potassium L-tyrosine O- 35 S-sulphate in the rat.
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Biomedical subjects
Publications and source records attributed to G M Powell.
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The metabolic fate of potassium dodecyl [(35)S]sulphate was studied in rats. Intraperitoneal and oral administration of the ester into free-ranging animals were followed by the excretion of the bulk of the radioactivity in the urine within 12hr., approximately 17% being eliminated as inorganic [(35)S]sulphate. Similar results were obtained in experiments in which potassium dodecyl [(35)S]sulphate was injected intravenously into anaesthetized rats with bile-duct and ureter cannulae. Analysis of urinary radioactivity revealed the presence of a new ester sulphate (metabolite A). This metabolite was isolated, purified and subsequently identified as the sulphate ester of 4-hydroxybutyric acid by paper, thin-layer and gas chromatography, by paper electrophoresis and by comparison of its properties with those of authentic butyric acid 4-sulphate. The identity of the metabolite was confirmed by isotope-dilution experiments. When either purified metabolite A or authentic potassium butyric acid 4[(35)S]-sulphate was administered to free-ranging rats the bulk of the radioactivity was eliminated unchanged in the urine within 12hr., approx. 20% of the dose appearing as inorganic [(35)S]sulphate. Whole-body radioautography and isolated-liver-perfusion experiments implicated the liver as the major site of metabolism of potassium dodecyl [(35)S]sulphate. It is suggested that butyric acid 4-sulphate probably arises by omega-oxidation of dodecyl sulphate to a fatty acid-like compound, which is then degraded by beta-oxidation.
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The metabolic fate of dipotassium 2-hydroxy-5-nitrophenyl [(35)S]sulphate ([(35)S]NCS), a chromogenic substrate for lysosomal arylsulphatases A and B, has been studied in rats. Intraperitoneal injection of [(35)S]NCS into free-ranging animals is followed by excretion of the bulk of the radioactivity in the urine within 24hr., less than 13% being eliminated as inorganic [(35)S]sulphate. Most of the urinary radioactivity can be accounted for as [(35)S]NCS, but small amounts of a labelled metabolite are also present. Experiments in which [(35)S]NCS was injected intravenously into anaesthetized rats with bile-duct and bladder cannulae confirm that the ester is rapidly excreted in the urine. However, small amounts of radioactivity appear in bile, mainly in the form of the metabolite detected in urine. When [(35)S]NCS is perfused through the isolated rat liver, about 35% of the dose is hydrolysed within 3hr. Similar results are obtained if [(35)S]NCS is injected into anaesthetized rats in which kidney function has been eliminated by ligature of the renal pedicles. The labelled metabolite has been isolated from bile obtained by perfusing several rat livers with blood containing a total of 100mg. of [(35)S]NCS. It has been identified as 2-beta-glucuronosido-5-nitrophenyl [(35)S]sulphate. The implications of the various findings are discussed. The Appendix describes the preparation of [(35)S]NCS.
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