title: [Concurrence of multiple and integrated mechanisms in the modulation of enzyme activities: significance for the regulation of metabolic fluxes].
abstract: The activity of some enzymes in a given metabolic pathway is modulated through multiple mechanisms, which operate in a simultaneous and coherent way to produce either stimulation or inhibition. The operation of these mechanisms is illustrated with several enzymes involved in glucose metabolism, by choosing examples from the presentations at the Symposium. Thus the reciprocal interactions of the regulatory mechanisms acting upon hexokinase D ('glucokinase'), phosphofructokinase, fructose 1,6-bisphosphatase and pyruvate kinase were discussed, as well as their relationships with the induction of enzyme conformational changes. In addition, the effects of covalent interconversions on glutamine synthetase activity were briefly analyzed. An outstanding feature exhibited by all these enzymes is the display of a great number of elasticity coefficients, which are differential quotients measuring the dependence of enzymatic activity on each variable that modulates it. A general assumption is that these enzymes make an important contribution to the control of the metabolic flux in which they participate. The flux control, however, appears to be shared in different degrees by all the components of the system, and may be quantified through the differential quotient denominated control coefficient. Some of the problems that emerge in any attempt to estimate these coefficients in the living cells are discussed. The problems derive partly from the complex subcellular structure, the formation of functional compartments resulting from reversible association of the enzymes, one to another and to different cellular components, and the actual state of cell water. These problems make that the results obtained with purified and highly diluted enzymes in most enzymological studies should not be extrapolated directly to what happens in vivo, without a careful evaluation of each particular case. The regulatory role of enzyme activity of fructose 2,6-bisphosphate and its eventual participation as an intermediary in the hormonal control of glycolytic and gluconeogenic fluxes are emphasized. The regulation of yeast fructose 1,6-bisphosphate activity is discussed in relation to the eventual role of allosteric modulators and covalents interconversions as signals for the initiation of intracellular degradation of the enzyme during catabolic inactivation.
mesh_terms: D002848:Chromatography, DEAE-Cellulose; D004789:Enzyme Activation; D006597:Fructose-Bisphosphatase / Q000378:metabolism*; D005943:Gluconeogenesis; D006019:Glycolysis; D006593:Hexokinase / Q000378:metabolism*; D007700:Kinetics; D008433:Mathematics; D009249:NADP / Q000494:pharmacology; D010732:Phosphofructokinase-1 / Q000378:metabolism*; D011770:Pyruvate Kinase / Q000378:metabolism*
chemical_list: D009249:NADP; D006593:Hexokinase; D010732:Phosphofructokinase-1; D011770:Pyruvate Kinase; D006597:Fructose-Bisphosphatase
vernacular_title: Concurrencia de mecanismos múltiples e integrados en la modulación de la actividad enzimática: significado para la regulación de flujos metabólicos.