Multimodulation of enzyme activity

Publisher Summary This chapter discusses the multimodulation of enzyme activity. Multimodulation of enzyme activity arises from the accumulation in a given enzyme of several regulatory mechanisms, whether of different types—cooperative, allosteric, interconversion, or of the same type—multiple allosteric effects, or of any combination of these. Modulation of enzyme activity was considered initially as synonymous with feedback inhibition, typically by the end product. With time, some enzymes appeared to have more than one mechanism for modulation of activity. Eventually, plurality increased for certain enzymes from more than one to many modulation mechanisms, including both noncovalent and covalent types. Phosphorylase provided the first example for many aspects of metabolic regulation at the enzyme level. It shows that marked co-operativity for the substrate P i , is inhibited by glucose 6-phosphate (Glc 6-P) and can be activated by either noncovalent (adenosine monophosphate —AMP) or covalent (phosphorylation) modulation. The two activation mechanisms make excellent physiological sense—AMP serves as energy-need signal and the phosphorylation ultimately reflects hormonal control.