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Biochem J. Feb 15, 1986; 234(1): 169–174.
PMCID: PMC1146541

Kinetics of metabolic pathways. A system in vitro to study the control of flux.


A method for determining Control Coefficients is proposed for systems studied in vitro and applied to a model pathway. Rat liver extract, which converts glucose into glycerol 3-phosphate, was used with the addition to the incubation mixture of fructose-bisphosphate aldolase, triose-phosphate isomerase and glycerol-3-phosphate dehydrogenase as 'auxiliary' enzymes, which leaves all the control on the first three enzymes. The flux of the metabolic pathway was recorded by assaying NADH decay. Flux Control Coefficients (CJE) of hexokinase, glucose-6-phosphate isomerase and phosphofructokinase were calculated by titration of the system with increasing quantities of extraneous enzymes. It is shown that the summation property is fulfilled. The applicability of this procedure to study the control in any metabolic pathway is discussed. Possible relevance of the method to conditions in vivo and its limitations are considered.

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Selected References

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  • Castaño JG, Nieto A, Felíu JE. Inactivation of phosphofructokinase by glucagon in rat hepatocytes. J Biol Chem. 1979 Jul 10;254(13):5576–5579. [PubMed]
  • Fell DA, Sauro HM. Metabolic control and its analysis. Additional relationships between elasticities and control coefficients. Eur J Biochem. 1985 May 2;148(3):555–561. [PubMed]
  • Groen AK, Wanders RJ, Westerhoff HV, van der Meer R, Tager JM. Quantification of the contribution of various steps to the control of mitochondrial respiration. J Biol Chem. 1982 Mar 25;257(6):2754–2757. [PubMed]
  • Heinrich R, Rapoport TA. A linear steady-state treatment of enzymatic chains. General properties, control and effector strength. Eur J Biochem. 1974 Feb 15;42(1):89–95. [PubMed]
  • Heinrich R, Rapoport TA. A linear steady-state treatment of enzymatic chains. Critique of the crossover theorem and a general procedure to identify interaction sites with an effector. Eur J Biochem. 1974 Feb 15;42(1):97–105. [PubMed]
  • Rapoport TA, Heinrich R, Jacobasch G, Rapoport S. A linear steady-state treatment of enzymatic chains. A mathematical model of glycolysis of human erythrocytes. Eur J Biochem. 1974 Feb 15;42(1):107–120. [PubMed]
  • Heinrich R, Rapoport TA. Mathematical analysis of multienzyme systems. II. Steady state and transient control. Biosystems. 1975 Jul;7(1):130–136. [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 SM. The utility of mathematical models for the understanding of metabolic systems. Biochem Soc Trans. 1983 Jan;11(1):31–35. [PubMed]
  • Hers HG, Van Schaftingen E. Fructose 2,6-bisphosphate 2 years after its discovery. Biochem J. 1982 Jul 15;206(1):1–12. [PMC free article] [PubMed]
  • HIGGINS J. Analysis of sequential reactions. Ann N Y Acad Sci. 1963 May 10;108:305–321. [PubMed]
  • Kacser H. The control of enzyme systems in vivo: elasticity analysis of the steady state. Biochem Soc Trans. 1983 Jan;11(1):35–40. [PubMed]
  • Kacser H, Burns JA. The control of flux. Symp Soc Exp Biol. 1973;27:65–104. [PubMed]
  • Kacser H, Burns JA. MOlecular democracy: who shares the controls? Biochem Soc Trans. 1979 Oct;7(5):1149–1160. [PubMed]
  • Kacser H, Burns JA. The molecular basis of dominance. Genetics. 1981 Mar-Apr;97(3-4):639–666. [PMC free article] [PubMed]
  • LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed]
  • Meléndez-Hevia E, Siverio JM, Pérez JA. Studies on glycolysis in vitro: role of glucose phosphorylation and phosphofructokinase activity on total velocity. Int J Biochem. 1984;16(5):469–476. [PubMed]
  • Middleton RJ, Kacser H. Enzyme variation, metabolic flux and fitness: alcohol dehydrogenase in Drosophila melanogaster. Genetics. 1983 Nov;105(3):633–650. [PMC free article] [PubMed]
  • Pilkis SJ. Glucokinase of rat liver. Methods Enzymol. 1975;42:31–39. [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]
  • Savageau MA. Biochemical systems analysis. II. The steady-state solutions for an n-pool system using a power-law approximation. J Theor Biol. 1969 Dec;25(3):370–379. [PubMed]
  • Savageau MA. Parameter sensitivity as a criterion for evaluating and comparing the performance of biochemical systems. Nature. 1971 Feb 19;229(5286):542–544. [PubMed]
  • Savageau MA. Concepts relating the behavior of biochemical systems to their underlying molecular properties. Arch Biochem Biophys. 1971 Aug;145(2):612–621. [PubMed]
  • Waley SG. A note on the kinetics of multi-enzyme systems. Biochem J. 1964 Jun;91(3):514–517. [PMC free article] [PubMed]
  • Wanders RJ, Groen AK, Van Roermund CW, Tager JM. Factors determining the relative contribution of the adenine-nucleotide translocator and the ADP-regenerating system to the control of oxidative phosphorylation in isolated rat-liver mitochondria. Eur J Biochem. 1984 Jul 16;142(2):417–424. [PubMed]
  • Westerhoff HV, Groen AK, Wanders RJ. Modern theories of metabolic control and their applications (review). Biosci Rep. 1984 Jan;4(1):1–22. [PubMed]

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