Enzymatic cascades

FIGURE 15.19 The hormone-activated enzymatic cascade that leads to activation of glycogen phosphorylase. 

Strictly speaking a catalytic cascade process is one in which all of the catalysts (enzymes or chemocatalysts) are present in the reaction mixture from the outset. A one-pot process, on the other hand, is one in which several reactions are conducted sequentially in the same reaction vessel, without the isolation of intermediates. However, not all of the reactants or catalysts are necessarily present from the outset. Hence, a cascade process is by definition a one-pot process, but the converse is not necessarily true. Clearly a cascade process is a more elegant solution, but a one-pot process that is not, according to the strict definihon, a cascade reaction may have equal practical uhlity. In this chapter we shall be primarily concerned with enzymatic cascade processes, but the occasional chemocatalytic step may be included where relevant and sometimes a sequential one-pot procedure may slip through the net. 

A major advantage of enzymes as catalysts is that they are capable of inducing very high degrees of enantioselectivity and, consequently, they are particularly useful in the synthesis of enanhomerically pure compounds. In cases where the enanh-oselectivity is less than optimum it can generally be improved using protein engineering techniques such as in vitro evolution [10]. Hence, in this chapter we shall be mainly concerned with the application of enzymatic cascade processes to the... 

Cross-Talk Between Kallikreins A Possible Novel Enzymatic Cascade Pathway 39... 

Interactions between serine proteases are common, and substrates of serine proteases are usually other serine proteases that are activated from an inactive precursor [66]. The involvement of serine proteases in cascade pathways is well documented. One important example is the blood coagulation cascade. Blood clots are formed by a series of zymogen activations. In this enzymatic cascade, the activated form of one factor catalyzes the activation of the next factor. Very small amounts of the initial factors are sufficient to trigger the cascade because of the catalytic nature of the process. These numerous steps yield a large amplification, thus ensuring a rapid and amplified response to trauma. A similar mechanism is involved in the dissolution of blood clots. A third important example of the coordinated action of serine proteases is the intestinal digestive enzymes. The apoptosis pathway is another important example of coordinated action of other types of proteases. 

It appears that small groups of kallikreins may represent enzymatic cascade pathways in certain tissues. For example, it is very likely that at least three kallikreins, hK2, hK3, and hKl 1, which are present in seminal plasma at relatively very large concentrations, may coordinately act as a cascade enzymatic pathway, involved in semen liquefaction or other activities. In contrast, another group of kallikreins, including hK5 and hK7 and possibly many others, seem to be involved in skin desquamation. Similar cascade pathways may be operating in the breast, testis and other tissues. 

Yousef GM, Diamandis EP. Human tissue kallikreins A new enzymatic cascade pathway Biol Chem 2002 383 1045-1057. 

The Activity of Glutamine Synthetase Is Modulated by an Enzymatic Cascade... 

The activity of glutamine synthetase is also controlled by reversible covalent modification —the attachment of an AMP unit by a phosphodiester bond to the hydroxyl group of a specific tyrosine residue in each subunit (Figure 24.26). This adenylylated enzyme is less active and more susceptible to cumulative feedback inhibition than is the deadenylylated form. The covalently attached AMP unit is removed from the adenylylated enzyme by phosphorolysis. The attachment of an AMP unit is the final step in an enzymatic cascade that is initiated several steps back by reactants and immediate products in glutamine synthesis. 

Figure 11.3. Tire enzymatic cascade responsible for pho to ti ansduction.

In order to refine therapeutic regimes and thus prevent chemical warfare agent-induced excitatory neurodegeneration in exposed individuals (Figure 5.4), a more comprehensive characterization of the destructive signal-transduction mechanisms and intracellular enzymatic cascades associated with glutamate receptor mediated delayed excitotoxicity (PCD) is needed. Accordingly, the refinement of therapeutic... 

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