Enzyme Regulation
Part V. Summary
Enzymes are regulated by changes in their activity levels and by the amount of enzyme. We have discussed two types of Enzyme Activity Regulation: Noncovalent and Covalent. Noncovalent can often be called allosteric regulation. Allosteric regulation of activity will usually take the form of positive cooperativity where binding of the substrate leads to a higher activity form of the enzyme by a change its 3-D shape as the first molecule of substrate binds. The next molecule of substrate is now more easily bound because the enzyme has shifted into a higher activity form with a higher affinity for the substrate (ie a low Km and higher Vmax form of enzyme). We illustrated this with data and models for the comparison of oxygen loading to hemoglobin and myoglobin. Allosteric regulation (non-covalent regulation of enzyme activity) can also cause inhibition of enzyme activity, which was illustrated with the concept of 'Feedback Inhibition' of enzyme activity by a downstream product of the pathway. In general, non-covalent modification is useful for short term regulation of enzyme activity which can respond quickly to changes in cellular conditions. For example, when a lot of substrate is available for a short period of time, the enzyme shifts into a more active form to process that substrate and relaxes into its low activity form when the burst of substrate has been converted.
Longer term conversion of an enzyme into a more active state is most easily achieved by a covalent modification of the enzyme. We illustrated this by discussing cellular conditions where the cell has been sent a hormone signal which tells it to convert to a different metabolic pattern. Thus, a cascade of modifications take place in the cell's enzymes mediated by special regulatory enzymes (such as protein kinases leading to phosphorylation of other enzymes by using ATP) which covalently modify the enzymes response for metabolism. This changes the whole pattern of the cell from one metabolic state to another. I call this a shift in 'metabolic mode' since the cell starts doing things differently when stimulated by a hormone. Once the hormone signal dissipates, the cell will return to the original state via another set of enzymes acting on the metabolic enzymes. The second set of regulatory enzymes (such as protein phosphatases which remove the phosphate esters from the phosphorylated proteins) reverse the covalent modifications put in place by the first set of regulatory enzymes. An important principle is at work here: in order for cells to response to stimuli like hormones, there must be two sets of regulatory factors or enzymes: ones to change the metabolic mode of the cell and ones to reverse these changes in order to return the cell to its original metabolic mode.
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©Wilbur H. Campbell, 1995; wcampbel@mtu.edu