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      Inhibition of Erythrocyte Aminolevulinate Dehydratase by a 56.2-kD Peptide from Uremic Plasma

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          Among the abnormalities in erythrocyte porphyrin metabolism already described in patients with chronic renal failure on hemodialysis, a decrease in blood aminolevulinate dehydratase activity has been reported, suggesting the presence in uremic plasma of an inhibitor of the enzyme. The aim of this work has been to isolate and characterize such an inhibitor. Blood samples from 105 patients with chronic uremia were collected; plasma was applied to Sephadex G-100 columns and the fraction with the highest inhibiting capacity was identified and purified by subsequent SDS-polyacrylamide gel electrophoresis, followed by electroelution and electroblotting. It was demonstrated that the factor present in plasma of uremic patients inhibited blood aminolevulinate dehydratase in a concentration-dependent manner; its inhibitory properties were abolished after heat, trypsin and TCA treatment indicating its peptidic nature. The purified inhibitor has an apparent molecular mass of 56.2 kD, it inhibits blood aminolevulinate dehydratase in a competitive way and the K<sub>i</sub> value is 12×10<sup>–6</sup> M. The amino acid composition of the inhibitor has been determined and it has been found that its N-terminal amino acid is blocked. The isolated peptide may play a role in heme biosynthesis disturbances and in the pathogenesis of uremic anemia.

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          Studies on erythrocyte aminolaevulinate dehydratase I. Its purification and possible therapeutic applications


            Author and article information

            Nephron Exp Nephrol
            Cardiorenal Medicine
            S. Karger AG
            June 1999
            28 May 1999
            : 7
            : 3
            : 236-241
            aCentro de Investigaciones sobre Porfirinas y Porfirias (UBA-CONICET), bInstituto de Quimica y Fisico-Quimica Biologicas (UBA-CONICET) y cInstituto Argentino de Riñón y Transplante, Buenos Aires, Argentina; dHospital Universitario Doce de Octubre, Universidad de Madrid, España
            20607 Exp Nephrol 1999;7:236–241
            © 1999 S. Karger AG, Basel

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            Page count
            Figures: 2, Tables: 3, References: 20, Pages: 6
            Self URI (application/pdf): https://www.karger.com/Article/Pdf/20607
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