Di Meo, I., Colombelli, C., Srinivasan, B., de Villiers, M., Hamada, J., Jeong, S.Y., Fox, R., Woltjer, R.L., Tepper, P.G., Lahaye, L.L., Rizzetto, E., Harrs, C.H., de Boer, T., van der Zwaag, M., Jenko, B., Čusak, A., Pahor, J., Kosec, G., Grzeschik, N.A., Hayflick, S.J., Tiranti, V., Sibon, O.C.M. (2017). Acetyl-4'-phosphopantetheine is stable in serum and prevents phenotypes induced by pantothenate kinase deficiency.  Sci. Rep. 7(1): 11260.

FBrf0250479

Research paper

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.

PMC5595861 (PMC) (EuropePMC)