Control of Fluxes in Metabolic Networks

G. Basler, Z. Nikoloski, A. Larhlimi, A.-L. Barabasi, and Y.-Y. Liu.
Genome Research
7:26, 956-968 (2016).
May 18, 2016


Understanding the  control of large-scale metabolic networks is central to biology and medicine.  However, existing approaches either require specifying a cellular objective  or can only be used for small networks. We introduce new coupling types  describing the relations between reaction activities, and develop an  efficient computational framework, which does not require any cellular  objective for systematic studies of large-scale metabolism. We identify the  driver reactions facilitating control of 23 metabolic networks from all  kingdoms of life. We find that unicellular organisms require smaller degree  of control than multicellular organisms. Driver reactions are under complex  cellular regulation in Escherichia coli, indicating their preeminent role in  facilitating cellular control. In human cancer cells driver reactions play  pivotal roles in malignancy and represent potential therapeutic targets. The  developed framework helps us gain insights into regulatory principles of  diseases and facilitates design of engineering strategies at the interface of  gene regulation, signaling, and metabolism.

Related publications