Abstract

Gluconeogenic flux exceeds glycolytic flux at the hexose-phosphate steps when measured in extracts of kidney cortex from well-fed rats. Addition of AMP and/or fructose 2,6-bisphosphate to the assay medium partially eradicates the difference. Using principles developed by Kacser, H., and Burns, J. A. ((1973) in Rate Control of Biological Processes (Davies, D. D., ed) pp. 65-104, Cambridge University Press, London) and Heinrich R., and Rapoport T. A. ((1974) Eur. J. Biochem. 42, 97-105), flux control coefficients of enzymes participating in the pathway segments from glucose 6-phosphate to triose-phosphates and from glycerol 3-phosphate to glucose 6-phosphate were determined by additions of the respective enzyme to the system. Results show that the flux control coefficients are highly modulated by the presence of allosteric effectors, as might be expected according to the regulatory properties of phosphofructokinase and fructose-1,6-bisphosphatase purified from this origin. Measured reductions of fructose 2,6-bisphosphate and AMP levels during acidosis, starvation, or after phenylephrine treatment suggest that these changes contribute to enhanced gluconeogenesis under these conditions.

Highlights

  • Biochem. 42,97-105), flux control coefficients of endistribution of enzymes along the nephron, phosphofructokinase and pyruvate kinase activities arealso present (Ross and Guder, 1982; Guder and Ross, 1984; GarciaSalguero and Lupiaiiez, 1989a, 1989b) even in excess of that of phosphoenolpyruvate carboxykinase

  • The flux controltheoryhas been extensively ured reductionsof fructose 2,6-bisphosphate anAdMP applied in the study of several metabolic systems

  • 1981; Middleton and Kacser, 1983; Groen et al, 1982, 1986; Regen and Pilkis, 1984; Torres et al, 1986, 1988; Salter et al, 1986). This theory defines the flux control coefficients (FCC) for an enzyme as the fractional change in the flux along the pathway/fractional change in the activity of the Regulation of glycolysis and gluconeogenesis is extremely important in organs and tissuessharing both capabilities, such as theliver and kidney cortex

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Summary

Introduction

Biochem. 42,97-105), flux control coefficients of endistribution of enzymes along the nephron, phosphofructokinase and pyruvate kinase activities arealso present (Ross and Guder, 1982; Guder and Ross, 1984; GarciaSalguero and Lupiaiiez, 1989a, 1989b) even in excess of that of phosphoenolpyruvate carboxykinase 1981; Middleton and Kacser, 1983; Groen et al, 1982, 1986; Regen and Pilkis, 1984; Torres et al, 1986, 1988; Salter et al, 1986) This theory defines the flux control coefficients (FCC) for an enzyme as the fractional change in the flux along the pathway/fractional change in the activity of the Regulation of glycolysis and gluconeogenesis is extremely important in organs and tissuessharing both capabilities, such as theliver and kidney cortex. In the liver most gluconeogeniccontrol in some metabolic situations is exerted by pyruvate carboxylase (Groen et al, 1986), another important regulatory step is the interconversion between Fru-1,6Pzland Fru-6-P (Pilkis et al, 1988) Cycling between these metabolites is a well documented phenomenon in the liver (Van Schaftingen et al, 1980a, 1980b; Hers and Hue, 1983; Claus et al, 1984; Pilkis et al, 1986;Gil et al, 1986) and kidney cortex (Newsholme and Underwood, 1966;Hue, 1982)

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