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Biophys J, August 2002, p. 646-662, Vol. 83, No. 2

Description and Analysis of Metabolic Connectivity and Dynamics in the Human Red Blood Cell

Kenneth J. Kauffman,* John David Pajerowski,* Neema Jamshidi,dagger Bernhard O. Palsson,dagger and Jeremy S. Edwards*

 *Department of Chemical Engineering, University of Delaware, Newark, Delaware 19716 USA; and  dagger Department of Bioengineering, University of California-San Diego, La Jolla, California 92093 USA

The human red blood cell (hRBC) metabolic network is relatively simple compared with other whole cell metabolic networks, yet too complicated to study without the aid of a computer model. Systems science techniques can be used to uncover the key dynamic features of hRBC metabolism. Herein, we have studied a full dynamic hRBC metabolic model and developed several approaches to identify metabolic pools of metabolites. In particular, we have used phase planes, temporal decomposition, and statistical analysis to show hRBC metabolism is characterized by the formation of pseudoequilibrium concentration states. Such equilibria identify metabolic "pools" or aggregates of concentration variables. We proceed to define physiologically meaningful pools, characterize them within the hRBC, and compare them with those derived from systems engineering techniques. In conclusion, systems science methods can decipher detailed information about individual enzymes and metabolites within metabolic networks and provide further understanding of complex biological networks.

Biophys J, August 2002, p. 646-662, Vol. 83, No. 2
© 2002 by the Biophysical Society   0006-3495/02/08/646/17  $2.00


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