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Biophys J. Aug 2002; 83(2): 646–662.
PMCID: PMC1302176

Description and analysis of metabolic connectivity and dynamics in the human red blood cell.

Abstract

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.

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Selected References

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  • Ataullakhanov FI, Buravtsev VN, Zhabotinskiĩ AM, Norina SB, Pichugin AV. Vzaimodeĩstvie puti Embdena-Meiergofa i geksozomonofosfatnogo shunta v éritrotsitakh. Biokhimiia. 1981 Apr;46(4):723–731. [PubMed]
  • Bailey JE. Mathematical modeling and analysis in biochemical engineering: past accomplishments and future opportunities. Biotechnol Prog. 1998 Jan-Feb;14(1):8–20. [PubMed]
  • Brumen M, Heinrich R. A metabolic osmotic model of human erythrocytes. Biosystems. 1984;17(2):155–169. [PubMed]
  • Edwards JS, Palsson BO. Multiple steady states in kinetic models of red cell metabolism. J Theor Biol. 2000 Nov 7;207(1):125–127. [PubMed]
  • Heinrich R, Rapoport SM, Rapoport TA. Metabolic regulation and mathematical models. Prog Biophys Mol Biol. 1977;32(1):1–82. [PubMed]
  • Heinrich R, Rapoport TA. Linear theory of enzymatic chains; its application for the analysis of the crossover theorem and of the glycolysis of human erythrocytes. Acta Biol Med Ger. 1973;31(4):479–494. [PubMed]
  • Heinrich R, Rapoport TA. Mathematical analysis of multienzyme systems. II. Steady state and transient control. Biosystems. 1975 Jul;7(1):130–136. [PubMed]
  • Holzhütter HG, Jacobasch G, Bisdorff A. Mathematical modelling of metabolic pathways affected by an enzyme deficiency. A mathematical model of glycolysis in normal and pyruvate-kinase-deficient red blood cells. Eur J Biochem. 1985 May 15;149(1):101–111. [PubMed]
  • Holzhütter HG, Schuster R, Buckwitz D, Jacobasch G. Mathematical modelling of metabolic pathways affected by an enzyme deficiency. Biomed Biochim Acta. 1990;49(8-9):791–800. [PubMed]
  • Jacobasch G, Holzhütter H, Bisdorf A. The energy metabolism of pyruvate kinase deficient red blood cells. Biomed Biochim Acta. 1983;42(11-12):S268–S272. [PubMed]
  • Jacobasch G, Holzhütter HG, Gerth C. Mathematical model of pyruvate kinase of chicken erythrocytes. Biomed Biochim Acta. 1983;42(11-12):S289–S290. [PubMed]
  • Jacobasch G, Rapoport SM. Hemolytic anemias due to erythrocyte enzyme deficiencies. Mol Aspects Med. 1996 Apr;17(2):143–170. [PubMed]
  • Jamshidi N, Edwards JS, Fahland T, Church GM, Palsson BO. Dynamic simulation of the human red blood cell metabolic network. Bioinformatics. 2001 Mar;17(3):286–287. [PubMed]
  • Joshi A, Palsson BO. Metabolic dynamics in the human red cell. Part I--A comprehensive kinetic model. J Theor Biol. 1989 Dec 19;141(4):515–528. [PubMed]
  • Joshi A, Palsson BO. Metabolic dynamics in the human red cell. Part II--Interactions with the environment. J Theor Biol. 1989 Dec 19;141(4):529–545. [PubMed]
  • Joshi A, Palsson BO. Metabolic dynamics in the human red cell. Part III--Metabolic reaction rates. J Theor Biol. 1990 Jan 9;142(1):41–68. [PubMed]
  • Joshi A, Palsson BO. Metabolic dynamics in the human red cell. Part IV--Data prediction and some model computations. J Theor Biol. 1990 Jan 9;142(1):69–85. [PubMed]
  • Lee ID, Palsson BO. A comprehensive model of human erythrocyte metabolism: extensions to include pH effects. Biomed Biochim Acta. 1990;49(8-9):771–789. [PubMed]
  • Lew VL, Bookchin RM. Volume, pH, and ion-content regulation in human red cells: analysis of transient behavior with an integrated model. J Membr Biol. 1986;92(1):57–74. [PubMed]
  • McIntyre LM, Thorburn DR, Bubb WA, Kuchel PW. Comparison of computer simulations of the F-type and L-type non-oxidative hexose monophosphate shunts with 31P-NMR experimental data from human erythrocytes. Eur J Biochem. 1989 Mar 15;180(2):399–420. [PubMed]
  • Mulquiney PJ, Kuchel PW. Model of 2,3-bisphosphoglycerate metabolism in the human erythrocyte based on detailed enzyme kinetic equations: computer simulation and metabolic control analysis. Biochem J. 1999 Sep 15;342(Pt 3):597–604. [PMC free article] [PubMed]
  • Palsson BO, Joshi A, Ozturk SS. Reducing complexity in metabolic networks: making metabolic meshes manageable. Fed Proc. 1987 Jun;46(8):2485–2489. [PubMed]
  • Palsson BO, Lightfoot EN. Mathematical modelling of dynamics and control in metabolic networks. I. On Michaelis-Menten kinetics. J Theor Biol. 1984 Nov 21;111(2):273–302. [PubMed]
  • Rae C, Berners-Price SJ, Bulliman BT, Kuchel PW. Kinetic analysis of the human erythrocyte glyoxalase system using 1H NMR and a computer model. Eur J Biochem. 1990 Oct 5;193(1):83–90. [PubMed]
  • Rapoport SM, Rapoport I, Schauer M, Heinrich R. The effect of pyruvate on glycolysis and the maintenance of adenine nucleotides in red cells. Acta Biol Med Ger. 1981;40(4-5):669–676. [PubMed]
  • Rapoport TA, Heinrich R. Mathematical analysis of multienzyme systems. I. Modelling of the glycolysis of human erythrocytes. Biosystems. 1975 Jul;7(1):120–129. [PubMed]
  • Rapoport TA, Heinrich R, Rapoport SM. The regulatory principles of glycolysis in erythrocytes in vivo and in vitro. A minimal comprehensive model describing steady states, quasi-steady states and time-dependent processes. Biochem J. 1976 Feb 15;154(2):449–469. [PMC free article] [PubMed]
  • Schuster R, Holzhütter HG, Jacobasch G. Interrelations between glycolysis and the hexose monophosphate shunt in erythrocytes as studied on the basis of a mathematical model. Biosystems. 1988;22(1):19–36. [PubMed]
  • Schuster R, Jacobasch G, Holzhütter H. Mathematical modelling of energy and redox metabolism of G6PD-deficient erythrocytes. Biomed Biochim Acta. 1990;49(2-3):S160–S165. [PubMed]
  • Schuster R, Jacobasch G, Holzhütter HG. Mathematical modelling of metabolic pathways affected by an enzyme deficiency. Energy and redox metabolism of glucose-6-phosphate-dehydrogenase-deficient erythrocytes. Eur J Biochem. 1989 Jul 1;182(3):605–612. [PubMed]
  • Thorburn DR, Kuchel PW. Computer simulation of the metabolic consequences of the combined deficiency of 6-phosphogluconolactonase and glucose-6-phosphate dehydrogenase in human erythrocytes. J Lab Clin Med. 1987 Jul;110(1):70–74. [PubMed]
  • Werner A, Heinrich R. A kinetic model for the interaction of energy metabolism and osmotic states of human erythrocytes. Analysis of the stationary "in vivo" state and of time dependent variations under blood preservation conditions. Biomed Biochim Acta. 1985;44(2):185–212. [PubMed]
  • Yoshida T, Dembo M. A thermodynamic model of hemoglobin suitable for physiological applications. Am J Physiol. 1990 Mar;258(3 Pt 1):C563–C577. [PubMed]

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