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Metabolomics and mass spectrometry imaging reveal channeled de novo purine synthesis in cells

2020; American Association for the Advancement of Science; Volume: 368; Issue: 6488 Linguagem: Inglês

10.1126/science.aaz6465

1095-9203

Vidhi Pareek, Hua Tian, Nicholas Winograd, Stephen J. Benkovic,

Enzyme Structure and Function

Signs of a metabolon in action Eukaryotic cells have a heterogeneous cytoplasm, with compartments large and small, membrane bound or not. Enzymes that catalyze the de novo synthesis of purine nucleotides, which are needed in rapidly dividing cells, are known to assemble into loosely associated, multienzyme structures called purinosomes, but the extent to which these structures are metabolically active has been less certain. Pareek et al. performed metabolomics to trace how purines are synthesized within purinosomes and used sophisticated mass spectrometry imaging to directly observe hotspots of metabolic activity within frozen HeLa cells (see the Perspective by Alexandrov). They found evidence for metabolic channeling between enzymes, which limits equilibration of intermediates formed in purinosomes with the bulk cellular metabolite pool. This process occurs specifically within purinosomes associated with mitochondria, because the input metabolites, glycine, aspartate, and formate, come from mitochondrial metabolism. Such channeling may help cells control the ratio and abundance of purine nucleotides. Science , this issue p. 283 ; see also p. 241