Network-based analysis of metabolic regulation in the human red blood cell

Nathan D. Price, Jennifer L. Reed, Jason A. Papin, Sharon J. Wiback, Bernhard O. Palsson

Rannsóknarafurð: Framlag til fræðitímaritsGreinritrýni

59 Tilvitnanir (Scopus)

Útdráttur

Reconstruction of cell-scale metabolic networks is now possible. A description of allowable metabolic network functions can be obtained using extreme pathways, which are the convex basis vectors of the solution space containing all steady state flux distributions. However, only a portion of these allowable network functions are physiologically possible due to kinetic and regulatory constraints. Methods are now needed that enable us to take a defined metabolic network and deduce candidate regulatory structures that control the selection of these physiologically relevant states. One such approach is the singular value decomposition (SVD) of extreme pathway matrices (P), which allows for the characterization of steady state solution spaces. Eigenpathways, which are the left singular vectors from the SVD of P, can be described and categorized by their biochemical function. SVD of P for the human red blood cell showed that the first five eigenpathways, out of a total of 23, effectively characterize all the relevant physiological states of red blood cell metabolism calculated with a detailed kinetic model. Thus, with five degrees of freedom the magnitude and nature of the regulatory needs are defined. Additionally, the dominant features of these first five eigenpathways described key metabolic splits that are indeed regulated in the human red blood cell. The extreme pathway matrix is derived directly from network topology and only knowledge of Vmax values is needed to reach these conclusions. Thus, we have implemented a network-based analysis of regulation that complements the study of individual regulatory events. This topological approach may provide candidate regulatory structures for metabolic networks with known stoichiometry but poorly characterized regulation.

Upprunalegt tungumálEnska
Síður (frá-til)185-194
Síðufjöldi10
FræðitímaritJournal of Theoretical Biology
Bindi225
Númer tölublaðs2
DOI
ÚtgáfustaðaÚtgefið - 21 nóv. 2003

Athugasemd

Funding Information:
The authors would like to thank Iman Famili and Dr. Radhakrishnan Mahadevan for insightful discussions, as well as Natalie Duarte for helpful feedback on this manuscript. We would like to acknowledge the support of the NIH (GM 57089) and the Whitaker Foundation (Graduate Research Fellowship to JP).

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