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

Sci Rep. 2017 Sep 12;7(1):11260. doi: 10.1038/s41598-017-11564-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Disease Models, Animal
  • Drosophila
  • Heredodegenerative Disorders, Nervous System / drug therapy*
  • Humans
  • Mice
  • Pantetheine / administration & dosage
  • Pantetheine / analogs & derivatives*
  • Pantetheine / chemical synthesis
  • Pantetheine / isolation & purification
  • Pantetheine / pharmacokinetics
  • Phosphotransferases (Alcohol Group Acceptor) / deficiency*
  • Serum / chemistry*
  • Treatment Outcome

Substances

  • Pantetheine
  • Phosphotransferases (Alcohol Group Acceptor)
  • pantothenate kinase
  • 4'-phosphopantetheine