1. Acetyl-4'-phosphopantetheine is stable in serum and prevents phenotypes induced by pantothenate kinase deficiency.
- Author
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Di Meo I, Colombelli C, Srinivasan B, de Villiers M, Hamada J, Jeong SY, Fox R, Woltjer RL, Tepper PG, Lahaye LL, Rizzetto E, Harrs CH, de Boer T, van der Zwaag M, Jenko B, Čusak A, Pahor J, Kosec G, Grzeschik NA, Hayflick SJ, Tiranti V, and Sibon OCM
- Subjects
- Animals, Cell Line, Disease Models, Animal, Drosophila, Humans, Mice, Pantetheine administration & dosage, Pantetheine chemical synthesis, Pantetheine isolation & purification, Pantetheine pharmacokinetics, Treatment Outcome, Heredodegenerative Disorders, Nervous System drug therapy, Pantetheine analogs & derivatives, Phosphotransferases (Alcohol Group Acceptor) deficiency, Serum chemistry
- 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.
- Published
- 2017
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