期刊
SCIENCE
卷 320, 期 5872, 页码 103-106出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1152241
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资金
- Direct For Biological Sciences [1048936] Funding Source: National Science Foundation
- Div Of Molecular and Cellular Bioscience [1048936] Funding Source: National Science Foundation
- NIA NIH HHS [R21 AG030949, R21 AG030949-01] Funding Source: Medline
Purines are synthesized de novo in 10 chemical steps that are catalyzed by six enzymes in eukaryotes. Studies in vitro have provided little evidence of anticipated protein- protein interactions that would enable substrate channeling and regulation of the metabolic flux. We applied fluorescence microscopy to HeLa cells and discovered that all six enzymes colocalize to form clusters in the cellular cytoplasm. The association and dissociation of these enzyme clusters can be regulated dynamically, by either changing the purine levels of or adding exogenous agents to the culture media. Collectively, the data provide strong evidence for the formation of a multi- enzyme complex, the purinosome, to carry out de novo purine biosynthesis in cells.
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