Novel insights into peptide amidation and amidating activity in the human circulation

Abstract C-terminal α-amidation is the final and essential step in the biosynthesis of several peptide hormones. Peptidylglycine α-amidating monooxygenase (PAM) is the only known enzyme to catalyse this reaction. PAM amidating activity (AMA) is known to be present in human circulation, but its physi...

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Autores principales:	Paul Kaufmann, Andreas Bergmann, Olle Melander
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/586afca4f3564839973bd01e8926ea08
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spelling	oai:doaj.org-article:586afca4f3564839973bd01e8926ea082021-12-02T17:06:31ZNovel insights into peptide amidation and amidating activity in the human circulation10.1038/s41598-021-95305-y2045-2322https://doaj.org/article/586afca4f3564839973bd01e8926ea082021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95305-yhttps://doaj.org/toc/2045-2322Abstract C-terminal α-amidation is the final and essential step in the biosynthesis of several peptide hormones. Peptidylglycine α-amidating monooxygenase (PAM) is the only known enzyme to catalyse this reaction. PAM amidating activity (AMA) is known to be present in human circulation, but its physiological role and significance as a clinical biomarker remains unclear. We developed a PAM-specific amidation assay that utilizes the naturally occurring substrate Adrenomedullin-Gly (ADM-Gly, 1–53). Using our amidation assay we quantified serum amidating activities in a large population-based cohort of more than 4900 individuals. A correlation of serum amidating activity with several clinical parameters including high blood pressure was observed. Increasing PAM-AMA was an independent predictor of hard outcomes related to hemodynamic stress such as cardiovascular mortality, atrial fibrillation and heart failure during long-term follow-up (8.8 ± 2.5 years). Moreover, results from an animal study in rats utilizing recombinant human PAM provide novel insights into the physiological role of circulating PAM and show its potential significance in circulating peptide amidation.Paul KaufmannAndreas BergmannOlle MelanderNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Paul Kaufmann Andreas Bergmann Olle Melander Novel insights into peptide amidation and amidating activity in the human circulation
description	Abstract C-terminal α-amidation is the final and essential step in the biosynthesis of several peptide hormones. Peptidylglycine α-amidating monooxygenase (PAM) is the only known enzyme to catalyse this reaction. PAM amidating activity (AMA) is known to be present in human circulation, but its physiological role and significance as a clinical biomarker remains unclear. We developed a PAM-specific amidation assay that utilizes the naturally occurring substrate Adrenomedullin-Gly (ADM-Gly, 1–53). Using our amidation assay we quantified serum amidating activities in a large population-based cohort of more than 4900 individuals. A correlation of serum amidating activity with several clinical parameters including high blood pressure was observed. Increasing PAM-AMA was an independent predictor of hard outcomes related to hemodynamic stress such as cardiovascular mortality, atrial fibrillation and heart failure during long-term follow-up (8.8 ± 2.5 years). Moreover, results from an animal study in rats utilizing recombinant human PAM provide novel insights into the physiological role of circulating PAM and show its potential significance in circulating peptide amidation.
format	article
author	Paul Kaufmann Andreas Bergmann Olle Melander
author_facet	Paul Kaufmann Andreas Bergmann Olle Melander
author_sort	Paul Kaufmann
title	Novel insights into peptide amidation and amidating activity in the human circulation
title_short	Novel insights into peptide amidation and amidating activity in the human circulation
title_full	Novel insights into peptide amidation and amidating activity in the human circulation
title_fullStr	Novel insights into peptide amidation and amidating activity in the human circulation
title_full_unstemmed	Novel insights into peptide amidation and amidating activity in the human circulation
title_sort	novel insights into peptide amidation and amidating activity in the human circulation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/586afca4f3564839973bd01e8926ea08
work_keys_str_mv	AT paulkaufmann novelinsightsintopeptideamidationandamidatingactivityinthehumancirculation AT andreasbergmann novelinsightsintopeptideamidationandamidatingactivityinthehumancirculation AT ollemelander novelinsightsintopeptideamidationandamidatingactivityinthehumancirculation
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Novel insights into peptide amidation and amidating activity in the human circulation

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