The article by Albert Goldbeter and Daniel E. Koshland, Jr. explores the amplification of sensitivity in biological systems through covalent modification. They examine the transient and steady-state behavior of a reversible covalent modification system, where small changes in the concentration of an effector can lead to significant changes in the amount of modified protein. This amplification is achieved when the modifying enzymes operate outside the region of first-order kinetics, leading to "zero-order ultrasensitivity." The authors derive mathematical equations to analyze the system and show that this sensitivity can be equivalent to that of allosteric proteins with high Hill coefficients. They also discuss the implications of this finding, including its potential role in biological control mechanisms and the possibility of enhanced sensitivity in multicyclic cascades. The study highlights the importance of covalent modification in generating sensitivity and the potential for biological systems to respond to small changes in environmental stimuli.The article by Albert Goldbeter and Daniel E. Koshland, Jr. explores the amplification of sensitivity in biological systems through covalent modification. They examine the transient and steady-state behavior of a reversible covalent modification system, where small changes in the concentration of an effector can lead to significant changes in the amount of modified protein. This amplification is achieved when the modifying enzymes operate outside the region of first-order kinetics, leading to "zero-order ultrasensitivity." The authors derive mathematical equations to analyze the system and show that this sensitivity can be equivalent to that of allosteric proteins with high Hill coefficients. They also discuss the implications of this finding, including its potential role in biological control mechanisms and the possibility of enhanced sensitivity in multicyclic cascades. The study highlights the importance of covalent modification in generating sensitivity and the potential for biological systems to respond to small changes in environmental stimuli.