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

Ivano Di Meo, Cristina Colombelli, Balaji Srinivasan, Marianne de Villiers, Jeffrey Hamada, Suh Y Jeong, Rachel Fox, Randall L Woltjer, Pieter G Tepper, Liza L Lahaye, Emanuela Rizzetto, Clara H Harrs, Theo de Boer, Marianne van der Zwaag, Branko Jenko, Alen Čusak, Jerca Pahor, Gregor Kosec, Nicola A Grzeschik, Susan J HayflickValeria Tiranti, Ody C M Sibon

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Abstract

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.

Original languageEnglish
Article number11260
Number of pages12
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 12-Sep-2017

Keywords

  • BRAIN IRON ACCUMULATION
  • COENZYME-A
  • ESCHERICHIA-COLI
  • PHOSPHOPANTOTHENOYLCYSTEINE SYNTHETASE
  • PANTETHINE RESCUES
  • COA SYNTHASE
  • NEURODEGENERATION
  • DROSOPHILA
  • IDENTIFICATION
  • BIOSYNTHESIS

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