Metabolic dynamics in the human red cell

Joshi, Abhay; Palsson, Bernhard Ø.

doi:10.1016/s0022-5193(89)80233-4

Cited by 146 publications

(38 citation statements)

References 19 publications

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“…The Mass Action ratio for the reaction catalysed by TPI in the normal in i o state has been reported by many different authors to be $ 3 (See Table 3.1 in [31]), while the equilibrium constant is around 20 [32,33]. The reason for this discrepancy is unclear given the very high catalytic capacity of TPI ; TPI has been described as the ' perfect enzyme ' [34]. An important point to note from Table 1 is that many of the reactions that have traditionally been treated as ' rapid-equilibrium ' reactions in the normal in i o steady-state situation (e.g.…”

Section: Values Of Equilibrium Constantsmentioning

confidence: 99%

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Model of 2,3-bisphosphoglycerate metabolism in the human erythrocyte based on detailed enzyme kinetic equations: equations and parameter refinement

Mulquiney

Kuchel

1999

Biochemical Journal

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Over the last 25 years, several mathematical models of erythrocyte metabolism have been developed. Although these models have identified the key features in the regulation and control of erythrocyte metabolism, many important aspects remain unexplained. In particular, none of these models have satisfactorily accounted for 2,3-bisphosphoglycerate (2,3-BPG) metabolism. 2,3-BPG is an important modulator of haemoglobin oxygen affinity, and hence an understanding of the regulation of 2,3-BPG concentration is important for understanding blood oxygen transport. A detailed, comprehensive, and hence realistic mathematical model of erythrocyte metabolism is presented that can explain the regulation and control of 2,3-BPG concentration and turnover. The model is restricted to the core metabolic pathways, namely glycolysis, the 2,3-BPG shunt and the pentose phosphate pathway (PPP), and includes membrane transport of metabolites, the binding of metabolites to haemoglobin and Mg# + , as well as pH effects on key enzymic reactions and binding processes. The

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Section: Values Of Equilibrium Constantsmentioning

confidence: 99%

“…Hence k i was set to $ 1 s −" . k i was taken to be 0.018 s −" for pyruvate transport [34] and 5.06i10 −$ s −" for lactate transport [35]. Since the pK a" value for pyruvate is 2.39, for most physiological pH values K eq l r. The K eq for lactate transport was modelled with eqn.…”

Section: Atpasementioning

confidence: 99%

Model of 2,3-bisphosphoglycerate metabolism in the human erythrocyte based on detailed enzyme kinetic equations: equations and parameter refinement

Mulquiney

Kuchel

1999

Biochemical Journal

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“…This approach dates back to the pioneering work of Garfinkel and Hess (1964) on glycolysis. Later on, this metabolic chain and related pathways of cellular energy metabolism were favoured subjects of successful mathematical modelling [e.g., Rapoport et al (1976), Werner and Heinrich (1985), Joshi and Palsson (1989), Joshi and Palsson (1990), Rizzi et al (1997), Mulquiney and Kuchel (1999a) and Mulquiney and Kuchel (1999b)]. However, in all these models, the structural properties of metabolic pathways, such as their stoichiometry and the values of the kinetic parameters, are input data.…”

Section: Introductionmentioning

confidence: 99%

Evolutionary Optimization of Metabolic Pathways. Theoretical Reconstruction of the Stoichiometry of ATP and NADH Producing Systems

Ebenhöh

Heinrich

2001

Bulletin of Mathematical Biology

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The structural design of ATP and NADH producing systems, such as glycolysis and the citric acid cycle (TCA), is analysed using optimization principles. It is assumed that these pathways combined with oxidative phosphorylation have reached, during their evolution, a high efficiency with respect to ATP production rates. On the basis of kinetic and thermodynamic principles, conclusions are derived concerning the optimal stoichiometry of such pathways. Extending previous investigations, both the concentrations of adenine nucleotides as well as nicotinamide adenine dinucleotides are considered variable quantities. This implies the consideration of the interaction of an ATP and NADH producing system, an ATP consuming system, a system coupling NADH consumption with ATP production and a system consuming NADH decoupled from ATP production. It is examined in what respect real metabolic pathways can be considered optimal by studying a large number of alternative pathways. The kinetics of the individual reactions are described by linear or bilinear functions of reactant concentrations. In this manner, the steady-state ATP production rate can be calculated for any possible ATP and NADH producing pathway. It is shown that most of the possible pathways result in a very low ATP production rate and that the very efficient pathways share common structural properties. Optimization with respect to the ATP production rate is performed by an evolutionary algorithm. The following results of our analysis are in close correspondence to the real design of glycolysis and the TCA cycle. (1) In all efficient pathways the ATP consuming reactions are located near the beginning. (2) In all efficient pathways NADH producing reactions as well as ATP producing reactions are located near the end. (3) The number of NADH molecules produced by the consumption of one energy-rich molecule (glucose) amounts to four in all efficient pathways. A distance measure and a measure for the internal ordering of reactions are introduced to study differences and similarities in the stoichiometries of metabolic pathways.

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“…Linear models can be accessed through analysis of input-output relations and certain stimulus-response experiments by applying advanced regression analysis (Schlosser et al, 1993) or other experimental methods developed within and around the metabolic control analysis (MCA) framework (Kacser and Burns, 1973;Heinrich and Rapoport, 1974;Cornish-Bowden and Cardenas, 1990;Fell, 1992). Nonlinear models, on the other hand, can be constructed when detailed kinetic expressions for each step in the reaction pathway are known or can be estimated (Joshi and Palsson, 1989;Gallazo and Bailey, 1990). Because of the greater data requirements for nonlinear model formulation and validation linear (or log-linear, see below) models will often be the only practically accessible description.…”

Section: Introductionmentioning

confidence: 99%

Analysis and design of metabolic reaction networks via mixed‐integer linear optimization

1996

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Metabolic dynamics in the human red cell

Cited by 146 publications

References 19 publications

Model of 2,3-bisphosphoglycerate metabolism in the human erythrocyte based on detailed enzyme kinetic equations: equations and parameter refinement

Model of 2,3-bisphosphoglycerate metabolism in the human erythrocyte based on detailed enzyme kinetic equations: equations and parameter refinement

Evolutionary Optimization of Metabolic Pathways. Theoretical Reconstruction of the Stoichiometry of ATP and NADH Producing Systems

Analysis and design of metabolic reaction networks via mixed‐integer linear optimization

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