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Global metabolic changes following loss of a feedback loop reveal dynamic steady states of the yeast metabolome

Paper ID Volume ID Publish Year Pages File Format Full-Text
31947 44858 2007 13 PDF Available
Title
Global metabolic changes following loss of a feedback loop reveal dynamic steady states of the yeast metabolome
Abstract

Metabolic enzymes control cellular metabolite concentrations dynamically in response to changing environmental and intracellular conditions. Such real-time feedback regulation suggests the global metabolome may sample distinct dynamic steady states, forming “basins of stability” in the energy landscape of possible metabolite concentrations and enzymatic activities. Using metabolite, protein and transcriptional profiling, we characterize three dynamic steady states of the yeast metabolome that form by perturbing synthesis of the universal methyl donor S-adenosylmethionine (AdoMet). Conversion between these states is driven by replacement of serine with glycine+formate in the media, loss of feedback inhibition control by the metabolic enzyme Met13, or both. The latter causes hyperaccumulation of methionine and AdoMet, and dramatic global compensatory changes in the metabolome, including differences in amino acid and sugar metabolism, and possibly in the global nitrogen balance, ultimately leading to a G1/S phase cell cycle delay. Global metabolic changes are not necessarily accompanied by global transcriptional changes, and metabolite-controlled post-transcriptional regulation of metabolic enzymes is clearly evident.

Keywords
Metabolomics; Metabolic profiling; Nuclear magnetic resonance; Mass spectrometry; One carbon metabolism
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Global metabolic changes following loss of a feedback loop reveal dynamic steady states of the yeast metabolome
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Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 9, Issue 1, January 2007, Pages 8–20
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
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Any Questions? feel free to contact us