Portal de Periódicos da CAPES

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

2017; Nature Portfolio; Volume: 7; Issue: 1 Linguagem: Inglês

10.1038/s41598-017-11564-8

2045-2322

Ivano Di Meo, Cristina Colombelli, Balaji Srinivasan, Marianne de Villiers, Jeffrey Hamada, Suh Young 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. Hayflick, Valeria Tiranti, Ody C.M. Sibon,

RNA regulation and disease

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.