Limits...
Growth-limiting intracellular metabolites in yeast growing under diverse nutrient limitations.

Boer VM, Crutchfield CA, Bradley PH, Botstein D, Rabinowitz JD - Mol. Biol. Cell (2009)

Bottom Line: Nitrogen (ammonium) and carbon (glucose) limitation were characterized by low intracellular amino acid and high nucleotide levels, whereas phosphorus (phosphate) limitation resulted in the converse.Low adenylate energy charge was found selectively in phosphorus limitation, suggesting the energy charge may actually measure phosphorus availability.A simple but physically realistic model involving the availability of these metabolites was adequate to account for cellular growth rate.

View Article: PubMed Central - PubMed

Affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.

ABSTRACT
Microbes tailor their growth rate to nutrient availability. Here, we measured, using liquid chromatography-mass spectrometry, >100 intracellular metabolites in steady-state cultures of Saccharomyces cerevisiae growing at five different rates and in each of five different limiting nutrients. In contrast to gene transcripts, where approximately 25% correlated with growth rate irrespective of the nature of the limiting nutrient, metabolite concentrations were highly sensitive to the limiting nutrient's identity. Nitrogen (ammonium) and carbon (glucose) limitation were characterized by low intracellular amino acid and high nucleotide levels, whereas phosphorus (phosphate) limitation resulted in the converse. Low adenylate energy charge was found selectively in phosphorus limitation, suggesting the energy charge may actually measure phosphorus availability. Particularly strong concentration responses occurred in metabolites closely linked to the limiting nutrient, e.g., glutamine in nitrogen limitation, ATP in phosphorus limitation, and pyruvate in carbon limitation. A simple but physically realistic model involving the availability of these metabolites was adequate to account for cellular growth rate. The complete data can be accessed at the interactive website http://growthrate.princeton.edu/metabolome.

Show MeSH
Growth rate slope for amino acids under nitrogen limitation. The positive growth rate slope found for every amino acid implies that, under nitrogen limitation, each amino acid's intracellular concentration increases with faster cellular growth rate (i.e., with partial relief of the nitrogen limitation). Amino acids are abbreviated by standard single-letter code.
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Figure 5: Growth rate slope for amino acids under nitrogen limitation. The positive growth rate slope found for every amino acid implies that, under nitrogen limitation, each amino acid's intracellular concentration increases with faster cellular growth rate (i.e., with partial relief of the nitrogen limitation). Amino acids are abbreviated by standard single-letter code.

Mentions: Examination of the growth rate slope across all amino acids revealed that the concentration of every amino acid dropped with increasingly severe ammonium limitation, with the strongest response for glutamine, histidine and arginine, which contain two, three, and four nitrogens, respectively (Figure 5). Both arginine and histidine receive nitrogen from glutamine, further implicating glutamine in control of nitrogen-limited growth.


Growth-limiting intracellular metabolites in yeast growing under diverse nutrient limitations.

Boer VM, Crutchfield CA, Bradley PH, Botstein D, Rabinowitz JD - Mol. Biol. Cell (2009)

Growth rate slope for amino acids under nitrogen limitation. The positive growth rate slope found for every amino acid implies that, under nitrogen limitation, each amino acid's intracellular concentration increases with faster cellular growth rate (i.e., with partial relief of the nitrogen limitation). Amino acids are abbreviated by standard single-letter code.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2801714&req=5

Figure 5: Growth rate slope for amino acids under nitrogen limitation. The positive growth rate slope found for every amino acid implies that, under nitrogen limitation, each amino acid's intracellular concentration increases with faster cellular growth rate (i.e., with partial relief of the nitrogen limitation). Amino acids are abbreviated by standard single-letter code.
Mentions: Examination of the growth rate slope across all amino acids revealed that the concentration of every amino acid dropped with increasingly severe ammonium limitation, with the strongest response for glutamine, histidine and arginine, which contain two, three, and four nitrogens, respectively (Figure 5). Both arginine and histidine receive nitrogen from glutamine, further implicating glutamine in control of nitrogen-limited growth.

Bottom Line: Nitrogen (ammonium) and carbon (glucose) limitation were characterized by low intracellular amino acid and high nucleotide levels, whereas phosphorus (phosphate) limitation resulted in the converse.Low adenylate energy charge was found selectively in phosphorus limitation, suggesting the energy charge may actually measure phosphorus availability.A simple but physically realistic model involving the availability of these metabolites was adequate to account for cellular growth rate.

View Article: PubMed Central - PubMed

Affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.

ABSTRACT
Microbes tailor their growth rate to nutrient availability. Here, we measured, using liquid chromatography-mass spectrometry, >100 intracellular metabolites in steady-state cultures of Saccharomyces cerevisiae growing at five different rates and in each of five different limiting nutrients. In contrast to gene transcripts, where approximately 25% correlated with growth rate irrespective of the nature of the limiting nutrient, metabolite concentrations were highly sensitive to the limiting nutrient's identity. Nitrogen (ammonium) and carbon (glucose) limitation were characterized by low intracellular amino acid and high nucleotide levels, whereas phosphorus (phosphate) limitation resulted in the converse. Low adenylate energy charge was found selectively in phosphorus limitation, suggesting the energy charge may actually measure phosphorus availability. Particularly strong concentration responses occurred in metabolites closely linked to the limiting nutrient, e.g., glutamine in nitrogen limitation, ATP in phosphorus limitation, and pyruvate in carbon limitation. A simple but physically realistic model involving the availability of these metabolites was adequate to account for cellular growth rate. The complete data can be accessed at the interactive website http://growthrate.princeton.edu/metabolome.

Show MeSH