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 ; Cusak, Alen ; Pahor, Jerca ; Kosec, Gregor ; Grzeschik, Nicola A. ; Hayflick, Susan J. ; Tiranti, Valeria ; Sibon, Ody C. M. (2017-09-12)

CITATION: Di Meo, I., et al. 2017. Acetyl-4′-phosphopantetheine is stable in serum and prevents phenotypes induced by pantothenate kinase deficiency. Scientific Reports, 7:11260, doi:10.1038/s41598-017-11564-8.

The original publication is available at https://www.nature.com

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.

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