Yeast increases glycolytic flux to support higher growth rates accompanied by decreased metabolite regulation and lower protein phosphorylation

Abstract

Supply of Gibbs free energy and precursors are vital for cellular function and cell metabolism have evolved to be tightly regulated to balance their supply and consumption. Precursors and Gibbs free energy are generated in the central carbon metabolism (CCM), and fluxes through these pathways are precisely regulated. However, how fluxes through CCM pathways are affected by posttranslational modification and allosteric regulation remains poorly understood. Here, we integrated multi-omics data collected under nine different chemostat conditions to explore how fluxes in the CCM are regulated in the yeast Saccharomyces cerevisiae . We deduced a pathway- and metabolism-specific CCM flux regulation mechanism using hierarchical analysis combined with mathematical modeling. We found that increased glycolytic flux associated with an increased specific growth rate was accompanied by a decrease in flux regulation by metabolite concentrations, including the concentration of allosteric effectors, and a decrease in the phosphorylation level of glycolytic enzymes.

PARROT: Prediction of enzyme abundances using protein-constrained metabolic models

“…Using lower λ values, the model prioritizes minimizing the enzyme usage distribution, aligning more closely with experimental observations. With a λ of 0, the model disregards metabolic fluxes entirely, enabling it to focus on solving for minimal enzyme usage redistribution, only calculating the flux distribution as a function of the former, mirroring what is observed in the cell [ 37 ]. Thus, by being proteome-aware, PARROT is better suited for simulations using pcGEMs than the quadratic and linear implementations of MOMA, given that higher participation of metabolic fluxes lowers the overall predictive performance.…”

Millifluidic magnetophoresis-based chip for age-specific fractionation: evaluating the impact of age on metabolomics and gene expression in yeast

“…66,68 Aging cells might face greater energy needs, necessitating adaptive measures for energy balance. Chen et al found that glycolytic flux rises with increased growth rates, 70 suggesting older cells may amplify glycolytic activity to meet energy requirements. Similarly, older cells might have reduced energy efficiency, compensating through heightened glycolytic activity and gene expression.…”

A conserved transcription factor controls gluconeogenesis via distinct targets in hypersaline-adapted archaea with diverse metabolic capabilities

“…Regulation of glycolytic and gluconeogenic activities in the cell is critical to generate energy and direct carbon flux in the face of variable environments and nutrient availability. In bacteria and eukaryotes, allosteric regulation plays an important role, though regulation at the transcriptional and post-transcriptional levels also occurs [1][2][3][4]. However, studies in archaea suggest that allosteric regulation of enzymes involved in central carbon metabolism is less prevalent (reviewed in Ref.…”