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

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.

Automated summary

The study reveals complex responses of cells to phosphate limitation, with extensive understanding of long-term effects but lacking a systems-level perspective. By categorizing phosphate utilization into cycles, sources, and sinks using yeast metabolic networks, metabolic reactions leading to sources or sinks of phosphate can be identified to illustrate how cells manage phosphate availability during transient limitations.