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Acetyl-4′-phosphopantetheine is stable in serum and prevents phenotypes induced by pantothenate kinase deficiency

Coenzyme A is an essential metabolite known for its central role in over one hundred cellular metabolic reactions. In cells, Coenzyme A is synthesized de novo in five enzymatic steps with vitamin B5 as the starting metabolite, phosphorylated by pantothenate kinase. Mutations in the pantothenate kina...

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Autores principales: Di Meo, Ivano, Colombelli, Cristina, Srinivasan, Balaji, de Villiers, Marianne, Hamada, Jeffrey, Jeong, Suh Y., Fox, Rachel, Woltjer, Randall L., Tepper, Pieter G., Lahaye, Liza L., Rizzetto, Emanuela, Harrs, Clara H., de Boer, Theo, van der Zwaag, Marianne, Jenko, Branko, Čusak, Alen, Pahor, Jerca, Kosec, Gregor, Grzeschik, Nicola A., Hayflick, Susan J., Tiranti, Valeria, Sibon, Ody C. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595861/
https://www.ncbi.nlm.nih.gov/pubmed/28900161
http://dx.doi.org/10.1038/s41598-017-11564-8
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author Di Meo, Ivano
Colombelli, Cristina
Srinivasan, Balaji
de Villiers, Marianne
Hamada, Jeffrey
Jeong, Suh Y.
Fox, Rachel
Woltjer, Randall L.
Tepper, Pieter G.
Lahaye, Liza L.
Rizzetto, Emanuela
Harrs, Clara H.
de Boer, Theo
van der Zwaag, Marianne
Jenko, Branko
Čusak, Alen
Pahor, Jerca
Kosec, Gregor
Grzeschik, Nicola A.
Hayflick, Susan J.
Tiranti, Valeria
Sibon, Ody C. M.
author_facet Di Meo, Ivano
Colombelli, Cristina
Srinivasan, Balaji
de Villiers, Marianne
Hamada, Jeffrey
Jeong, Suh Y.
Fox, Rachel
Woltjer, Randall L.
Tepper, Pieter G.
Lahaye, Liza L.
Rizzetto, Emanuela
Harrs, Clara H.
de Boer, Theo
van der Zwaag, Marianne
Jenko, Branko
Čusak, Alen
Pahor, Jerca
Kosec, Gregor
Grzeschik, Nicola A.
Hayflick, Susan J.
Tiranti, Valeria
Sibon, Ody C. M.
author_sort Di Meo, Ivano
collection PubMed
description Coenzyme A is an essential metabolite known for its central role in over one hundred cellular metabolic reactions. In cells, Coenzyme A is synthesized de novo in five enzymatic steps with vitamin B5 as the starting metabolite, phosphorylated by pantothenate kinase. Mutations in the pantothenate kinase 2 gene cause a severe form of neurodegeneration for which no treatment is available. One therapeutic strategy is to generate Coenzyme A precursors downstream of the defective step in the pathway. Here we describe the synthesis, characteristics and in vivo rescue potential of the acetyl-Coenzyme A precursor S-acetyl-4′-phosphopantetheine as a possible treatment for neurodegeneration associated with pantothenate kinase deficiency.
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spelling pubmed-55958612017-09-14 Acetyl-4′-phosphopantetheine is stable in serum and prevents phenotypes induced by pantothenate kinase deficiency Di Meo, Ivano Colombelli, Cristina Srinivasan, Balaji de Villiers, Marianne Hamada, Jeffrey Jeong, Suh Y. Fox, Rachel Woltjer, Randall L. Tepper, Pieter G. Lahaye, Liza L. Rizzetto, Emanuela Harrs, Clara H. de Boer, Theo van der Zwaag, Marianne Jenko, Branko Čusak, Alen Pahor, Jerca Kosec, Gregor Grzeschik, Nicola A. Hayflick, Susan J. Tiranti, Valeria Sibon, Ody C. M. Sci Rep Article Coenzyme A is an essential metabolite known for its central role in over one hundred cellular metabolic reactions. In cells, Coenzyme A is synthesized de novo in five enzymatic steps with vitamin B5 as the starting metabolite, phosphorylated by pantothenate kinase. Mutations in the pantothenate kinase 2 gene cause a severe form of neurodegeneration for which no treatment is available. One therapeutic strategy is to generate Coenzyme A precursors downstream of the defective step in the pathway. Here we describe the synthesis, characteristics and in vivo rescue potential of the acetyl-Coenzyme A precursor S-acetyl-4′-phosphopantetheine as a possible treatment for neurodegeneration associated with pantothenate kinase deficiency. Nature Publishing Group UK 2017-09-12 /pmc/articles/PMC5595861/ /pubmed/28900161 http://dx.doi.org/10.1038/s41598-017-11564-8 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Di Meo, Ivano
Colombelli, Cristina
Srinivasan, Balaji
de Villiers, Marianne
Hamada, Jeffrey
Jeong, Suh Y.
Fox, Rachel
Woltjer, Randall L.
Tepper, Pieter G.
Lahaye, Liza L.
Rizzetto, Emanuela
Harrs, Clara H.
de Boer, Theo
van der Zwaag, Marianne
Jenko, Branko
Čusak, Alen
Pahor, Jerca
Kosec, Gregor
Grzeschik, Nicola A.
Hayflick, Susan J.
Tiranti, Valeria
Sibon, Ody C. M.
Acetyl-4′-phosphopantetheine is stable in serum and prevents phenotypes induced by pantothenate kinase deficiency
title Acetyl-4′-phosphopantetheine is stable in serum and prevents phenotypes induced by pantothenate kinase deficiency
title_full Acetyl-4′-phosphopantetheine is stable in serum and prevents phenotypes induced by pantothenate kinase deficiency
title_fullStr Acetyl-4′-phosphopantetheine is stable in serum and prevents phenotypes induced by pantothenate kinase deficiency
title_full_unstemmed Acetyl-4′-phosphopantetheine is stable in serum and prevents phenotypes induced by pantothenate kinase deficiency
title_short Acetyl-4′-phosphopantetheine is stable in serum and prevents phenotypes induced by pantothenate kinase deficiency
title_sort acetyl-4′-phosphopantetheine is stable in serum and prevents phenotypes induced by pantothenate kinase deficiency
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595861/
https://www.ncbi.nlm.nih.gov/pubmed/28900161
http://dx.doi.org/10.1038/s41598-017-11564-8
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