Optimal flux states, reaction replaceability and response to knockouts in the human red blood cell

TL;DR

This paper investigates the metabolic robustness of the human red blood cell by analyzing optimal flux states, reaction replaceability, and responses to gene knockouts, combining combinatorial and sampling methods for comprehensive insights.

Contribution

It introduces a novel approach integrating combinatorial and sampling techniques to map reaction replaceability and response to knockouts in human red blood cell metabolism.

Findings

Complete map of potential damage from enzyme deficiencies

Correlation between network topology and flux dynamics

Insights into metabolic robustness and vulnerability

Abstract

Characterizing the capabilities, criticalities and response to perturbations of genome-scale metabolic networks is a basic problem with important applications. A key question concerns the identification of the potentially most harmful knockouts. The integration of combinatorial methods with sampling techniques to explore the space of viable flux states may provide crucial insights on this issue. We assess the replaceability of every metabolic conversion in the human red blood cell by enumerating the alternative paths from substrate to product, obtaining a complete map of the potential damage of single enzymopathies. Sampling the space of optimal flux states in the healthy and in the mutated cell reveals both correlations and complementarity between topologic and dynamical aspects.