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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
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Summary
This summary is machine-generated.

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.

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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.