Cycles, sources, and sinks: Conceptualizing how phosphate balance modulates carbon flux using yeast metabolic networks

Elife. 2021 Feb 5:10:e63341. doi: 10.7554/eLife.63341.

Abstract

Phosphates are ubiquitous molecules that enable critical intracellular biochemical reactions. Therefore, cells have elaborate responses to phosphate limitation. Our understanding of long-term transcriptional responses to phosphate limitation is extensive. Contrastingly, a systems-level perspective presenting unifying biochemical concepts to interpret how phosphate balance is critically coupled to (and controls) metabolic information flow is missing. To conceptualize such processes, utilizing yeast metabolic networks we categorize phosphates utilized in metabolism into cycles, sources and sinks. Through this, we identify metabolic reactions leading to putative phosphate sources or sinks. With this conceptualization, we illustrate how mass action driven flux towards sources and sinks enable cells to manage phosphate availability during transient/immediate phosphate limitations. We thereby identify how intracellular phosphate availability will predictably alter specific nodes in carbon metabolism, and determine signature cellular metabolic states. Finally, we identify a need to understand intracellular phosphate pools, in order to address mechanisms of phosphate regulation and restoration.

Keywords: carbon metabolism; computational biology; gene expression; mass action; metabolic flux; metabolic networks; phosphate; systems biology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carbon / metabolism
  • Carbon Cycle*
  • Metabolic Networks and Pathways*
  • Phosphates / metabolism*
  • Saccharomyces cerevisiae / metabolism*

Substances

  • Phosphates
  • Carbon