Thiophosphate Analogs of Coenzyme A and Its Precursors-Synthesis, Stability, and Biomimetic Potential.
CoA
CoA biosynthesis
CoA deficiency
CoA degradation
HoPan
NBIA
Nudt7
PKAN
PPanSH
phosphorothioate
Journal
Biomolecules
ISSN: 2218-273X
Titre abrégé: Biomolecules
Pays: Switzerland
ID NLM: 101596414
Informations de publication
Date de publication:
01 08 2022
01 08 2022
Historique:
received:
28
06
2022
revised:
28
07
2022
accepted:
29
07
2022
entrez:
26
8
2022
pubmed:
27
8
2022
medline:
30
8
2022
Statut:
epublish
Résumé
Coenzyme A (CoA) is ubiquitous and essential for key cellular processes in any living organism. Primary degradation of CoA occurs by enzyme-mediated pyrophosphate hydrolysis intracellularly and extracellularly to form adenosine 3',5'-diphosphate and 4'-phosphopantetheine (PPanSH). The latter can be recycled for intracellular synthesis of CoA. Impairments in the CoA biosynthetic pathway are linked to a severe form of neurodegeneration with brain iron accumulation for which no disease-modifying therapy is available. Currently, exogenous administration of PPanSH is examined as a therapeutic intervention. Here, we describe biosynthetic access to thiophosphate analogs of PPanSH, 3'-dephospho-CoA, and CoA. The stabilizing effect of thiophosphate modifications toward degradation by extracellular and peroxisomal enzymes was studied in vitro. Experiments in a CoA-deficient cell model suggest a biomimetic potential of the PPanSH thiophosphate analog P
Identifiants
pubmed: 36008959
pii: biom12081065
doi: 10.3390/biom12081065
pmc: PMC9405834
pii:
doi:
Substances chimiques
Phosphates
0
Coenzyme A
SAA04E81UX
thiophosphoric acid
TYM4M7EWCW
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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