The Role of Zero-Order Ultrasensitivity Amplification in the Regulation of the Glycogen Phosphorylase A — Phosphorylase B Cycle
Biological signaling systems generally contain amplification steps to offset attenuations of the signal. Diminution of signal may be caused by dilution of messenger molecules, desensitization of receptors and by the activities of specific antagonistic processes. Two general classifications of biochemical amplification have been described by Koshland et al. (1). Magnitude amplification depends on the ability of a single enzyme molecule to catalyze the conversion of many molecules of substrate. Several steps of magnitude amplification may be linked in a cascade such as found in blood clotting or hormonally induced glycogenolysis. Sensitivity amplification is a measure of the fractional change in response compared to the fractional change in signal. In the case of sensitivity amplification, the signal may be a small change in a relatively large concentration of stimulatory species with the response being a relatively larger change in a pre-existing level of output molecules. For example, a 10% increase in the concentration of signal molecules causing a 50% increase in the concentration of responding species yields a sensitivity amplification factor of 5. Sensitivity amplification is known to arise in three circumstances: Positive cooperativity, multiple inputs of a single effector and zero-order ultrasensitivity. The zero-order effect may occur in regulatory systems utilizing cyclic activation-deactivation through covalent modification of an enzyme protein. The regulated enzyme must be present at a concentration higher than the Michaelis constants of either or both of the two converter enzymes.
KeywordsMole Fraction Glycogen Phosphorylase Fractional Change Response Coefficient Phosphorylase Kinase
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