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Hierarchical and Programmable One-Pot Oligosaccharide Synthesis
Published on: September 6, 2019
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Methionine coordinates a hierarchically organized anabolic program enabling proliferation.
Adhish S Walvekar1, Rajalakshmi Srinivasan1, Ritu Gupta1
1Institute for Stem Cell biology and Regenerative Medicine (inStem), NCBS-TIFR campus, Bangalore 560065, India.
Molecular Biology of the Cell
|October 26, 2018
Summary
Methionine reprograms cells for growth during amino acid scarcity by activating a metabolic network. This involves the pentose phosphate pathway, glutamate dehydrogenase, and PLP-dependent transamination, creating a hierarchical anabolic program.
Area of Science:
- Cellular metabolism
- Molecular biology
- Biochemistry
Background:
- Methionine availability influences cellular reprogramming under amino acid limitation.
- The precise mechanisms driving this methionine-mediated anabolic program are not fully understood.
Purpose of the Study:
- To elucidate the organizational basis of the methionine-mediated anabolic program in yeast.
- To identify key metabolic nodes and regulatory factors involved in cellular adaptation to methionine availability.
Main Methods:
- Comparative transcriptome analysis.
- Biochemical assays.
- Metabolic flux analysis.
Main Results:
- Methionine enhances the activity of a central metabolic node comprising the pentose phosphate pathway (PPP), glutamate dehydrogenase (GDH)-dependent synthesis, and pyridoxal-5-phosphate (PLP)-dependent transamination.
- This PPP-GDH-PLP node supplies essential precursors for amino acid and nucleotide biosynthesis.
- Methionine-dependent induction of rate-limiting amino acid biosynthesis steps and co-option of the Gcn4p regulator sustain the anabolic program.
Conclusions:
- A hierarchical metabolic framework explains how methionine triggers an anabolic switch.
- Methionine availability orchestrates a coordinated metabolic response to support cell proliferation under nutrient stress.
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