Quantitative Analysis of the Effective Functional Structure in Yeast Glycolysis

TL;DR

This study uses transfer entropy to analyze the dynamic functional connectivity of yeast glycolysis, revealing key enzymes and invariant properties in the system's complex oscillatory behavior.

Contribution

It introduces a quantitative, dynamical analysis of enzyme interactions in yeast glycolysis using transfer entropy, highlighting the key role of phosphofructokinase.

Findings

Identification of a dynamical effective functional structure in glycolysis.

Discovery of a metabolic invariant constraining enzyme interactions.

Confirmation of phosphofructokinase as the main causal source.

Abstract

Yeast glycolysis is considered the prototype of dissipative biochemical oscillators. In cellular conditions, under sinusoidal source of glucose, the activity of glycolytic enzymes can display either periodic, quasiperiodic or chaotic behavior. In order to quantify the functional connectivity for the glycolytic enzymes in dissipative conditions we have analyzed different catalytic patterns using the non-linear statistical tool of Transfer Entropy. The data were obtained by means of a yeast glycolytic model formed by three delay differential equations where the enzymatic speed functions of the irreversible stages have been explicitly considered. These enzymatic activity functions were previously modeled and tested experimentally by other different groups. In agreement with experimental conditions, the studied time series corresponded to a quasi-periodic route to chaos. The results of the analysis are three-fold: first, in addition to the classical topological structure characterized by the specific location of enzymes, substrates, products and feedback regulatory metabolites, an effective functional structure emerges in the modeled glycolytic system, which is dynamical and characterized by notable variations of the functional interactions. Second, the dynamical structure exhibits a metabolic invariant which constrains the functional attributes of the enzymes. Finally, in accordance with the classical biochemical studies, our numerical analysis reveals in a quantitative manner that the enzyme phosphofructokinase is the key-core of the metabolic system, behaving for all conditions as the main source of the effective causal flows in yeast glycolysis.