Amplification cascade

Another important characteristic of these enzymes is the amplification cascade involving phosphorylase kinase and phosphorylase. The chemical signal, here phosphorylase kinase, can react with many molecules of phosphorylase b which, in turn, produce phosphorylase a which converts glycogen into glucose 1-phosphate. 

The prevalence of compounds that interfere with settlement and metamorphosis of complex organisms like barnacles is a logical consequence of the complexity of the biochemical pathways controlling metamorphosis. There is evidence that these pathways begin with chemoreceptors coupled to neuronal, hormonal, and metabolic control processes through classic amplification cascades that include second messengers20,22,88 102 that are stimulated by changes in ion permeability.109... 

Metarhodopsin II is the excited form of rhodopsin that initiates the guanine nucleotide amplification cascade that causes nerve stimulation. The final event is a hyperpolarization of the outer section membrane of the rod or cone caused by the closure of sodium and calcium channels through the membrane - excitation of a single molecule of rhodopsin, the action of a single photon, causes a drop of 1 pA in the normal dark current across this membrane... 

The cAMP system also derives some of its specificity from the proteins that are substrates for cAMP-dependent protein kinase. It is an indirect regulatory system, since cAMP modulates the activity of cAMP-dependent protein kinase and the kinase, in turn, affects the activities of a variety of metabolic enzymes or other proteins. This indirectness is the basis for amplification of the hormonal signal. Activation of adenylate cyclase by binding of a hormone molecule to a receptor causes formation of many molecules of cAMP and allows activation of many molecules of the protein kinase, each of which in turn can phosphorylate many enzymes or other proteins. This amplification cascade accounts in part for the extreme sensitivity of metabolic responses to small changes in hormone concentrations. Finally, the response to increased cAMP concentrations within a cell usually involves several metabolic pathways and a variety of enzymes or other proteins. 

Like many other proteases, the caspases are formed as inactive proenzymes of 30-50 kDa and are activated by proteolytic processing. The proenzymes have an N-terminal prodomain followed by sequences encoding first a large (a-chain) and then a small (fi-chain) subunit. The large and small subunits of the caspase are formed from the proenzyme by proteolysis at Asp-X sites. These internal cleavage sites are consistent with the ability to autoactivate or to activate other caspases as part of an amplification cascade. 

Fig. 8.8 The Host Response Protein Amplification Cascade (HR-PAC). According to this new theory, disease-specific enzymes act as generators of specifically modified marker proteins which can serve as valuable biomarkers by signaling a disease in a...

In an amplification cascade, each step greatly increases the amount of substrate available for the next step, so that a very large amount of the final product is made. Consider the following hypothetical amplification cascade ... 

Reflect and Apply The epinephrine-mediated amplification cascade of Figure 24.14 has six steps, all of which are catalytic with one exception. This cascade leads to the activation of glycogen phosphorylase. This enzyme acts in turn on glycogen to yield glucose-1-phosphate (G-l-P). 

Reflect and Apply How is the amplification cascade of Question 47 reversed ... 

Amplification cascades, such as the one involved in blood clotting, are important in a number of regulatory processes. Figure 10.7 shows a hypothetical cascade involving conversions between inactive and active forms of enzymes. Active enzyme A serves as a catalyst for the activation of enzyme B. Active B in turn activates C, and so forth. Assume that each enzyme in the pathway has a turnover number of 10. How many molecules of enzyme D will be activated per unit time when one molecule of active enzyme A is produced per unit time ... 

Distinguish between the active and inactive forms of glycogen synthase in terms of their states of phosphorylation and contrast the effects of phosphorylation on glycogen synthase and glycogen phosphorylase. Appreciate the reciprocal regulation strategies employed and the consequences of amplification cascades. 

The low-capacity blood supply to the type Ilb fibers (Example 13.21) may limit the amount of epinephrine available to bind to the receptors, but the operation of the phosphorylation amplification cascade more than compensates and rapidly leads to full activation of glycogen phosphorylase. 

Chelyapov, N. (2006). Allosteric aptamers controlling a signal amplification cascade allow visual detection of molecules at picomolar concentrations. Biochemistry 45, 2461-2466. 

For many compounds activation of the innate immune system has been shown to act as a deleterious amplification cascade that markedly exacerbates liver toxicity. In addition, some drugs have the ability to cause liver injury... 

Metarhodopsin II is the excited form of rhodopsin, which initiates a guanine nucleotide amplification cascade (section 10.3.1) and then initiates a nerve impulse. 

FIGURE 10.8 Amplification cascade in the regulation of glycogen metabolism in skeletal muscle cells by adrenaline... 

The system is called an amplification cascade since the binding of one molecule of adrenaline can cause the formation of numerous molecules of cAMP which may dissociate protein kinase A molecules thereby sequentially promoting the activation of more molecules of phosphorylase kinase... 

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