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

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          Abstract

          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

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            Author and article information

            Journal
            EXN
            Nephron Exp Nephrol
            10.1159/issn.1660-2129
            Cardiorenal Medicine
            S. Karger AG
            1660-2129
            1999
            June 1999
            28 May 1999
            : 7
            : 3
            : 236-241
            Affiliations
            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
            Article
            20607 Exp Nephrol 1999;7:236–241
            10.1159/000020607
            10352364
            © 1999 S. Karger AG, Basel

            Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

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

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