Metabolomics and mass spectrometry imaging reveal channeled de novo purine synthesis in cells.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
17 04 2020
17 04 2020
Historique:
received:
26
09
2019
accepted:
25
02
2020
entrez:
18
4
2020
pubmed:
18
4
2020
medline:
21
5
2020
Statut:
ppublish
Résumé
Metabolons, multiprotein complexes consisting of sequential enzymes of a metabolic pathway, are proposed to be biosynthetic "hotspots" within the cell. However, experimental demonstration of their presence and functions has remained challenging. We used metabolomics and in situ three-dimensional submicrometer chemical imaging of single cells by gas cluster ion beam secondary ion mass spectrometry (GCIB-SIMS) to directly visualize de novo purine biosynthesis by a multienzyme complex, the purinosome. We found that purinosomes comprise nine enzymes that act synergistically, channeling the pathway intermediates to synthesize purine nucleotides, increasing the pathway flux, and influencing the adenosine monophosphate/guanosine monophosphate ratio. Our work also highlights the application of high-resolution GCIB-SIMS for multiplexed biomolecular analysis at the level of single cells.
Identifiants
pubmed: 32299949
pii: 368/6488/283
doi: 10.1126/science.aaz6465
pmc: PMC7494208
mid: NIHMS1608433
doi:
Substances chimiques
Multienzyme Complexes
0
Purines
0
purine
W60KTZ3IZY
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
283-290Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM024129
Pays : United States
Organisme : NIGMS NIH HHS
ID : R37 GM024129
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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