Superiority of interconvertible enzyme cascades in metabolic regulation: analysis of monocyclic systems.
A theoretical analysis of monocyclic cascade models shows that the steady-state fraction of covalently modified interconvertible enzyme is a function of 10 different cascade parameters. Because each parameter can be varied independently, or several can be varied simultaneously, by single or multiple allosteric interactions of ligands with one or more of the cascade enzymes, interconvertible enzymes are exquisitely designed for the rigorous control of key metabolic steps. Compared with other reglatory enzymes, they can respond to a greater number of allosteric stimuli, they exhibit greater flexibility in overall control patterns, and they can generate a greatly amplified response to primary allosteric interactions of effectors with the converter enzymes. Contrary to earlier views, the decomposition of ATP associated with cyclic coupling of the covalent modification and demodification reactions is not a futile process. ATP decomposition supplies the energy needed to maintain concentrations of modified enzyme at steady-state levels that are in excess of those obtainable at true thermodynamic equilibrium.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000494:Allosteric Regulation; D003201:Computers; D004798:Enzymes / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D008660:Metabolism; D008954:Models, Biological; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism
D004798:Enzymes; D008024:Ligands; D011768:Pyruvate Dehydrogenase Complex; D000255:Adenosine Triphosphate
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